{"id":12877,"date":"2026-03-13T12:17:55","date_gmt":"2026-03-13T12:17:55","guid":{"rendered":"https:\/\/csiag.de\/?p=12877"},"modified":"2026-04-05T15:40:20","modified_gmt":"2026-04-05T15:40:20","slug":"opcoes-de-tratamento-do-linfoma","status":"publish","type":"post","link":"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/","title":{"rendered":"Linfoma - op\u00e7\u00f5es terap\u00eauticas"},"content":{"rendered":"<div id=\"ez-toc-container\" class=\"ez-toc-v2_0_85 counter-hierarchy ez-toc-counter ez-toc-grey ez-toc-container-direction\">\n<div class=\"ez-toc-title-container\">\n<p class=\"ez-toc-title\" style=\"cursor:inherit\">\u00cdndice<\/p>\n<span class=\"ez-toc-title-toggle\"><\/span><\/div>\n<nav><ul class='ez-toc-list ez-toc-list-level-1' ><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-1\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Wie_entstehen_Lymphom-Erkrankungen\" >Como \u00e9 que os linfomas se desenvolvem?<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-2\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Einleitung\" >Introdu\u00e7\u00e3o<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-3\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Ubersicht_der_Lymphomarten\" >Vis\u00e3o geral dos tipos de linfoma<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-4\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Hodgkin-Lymphom_ca_10-15_aller_Lymphome\" >Linfoma de Hodgkin (aprox. 10-15% de todos os linfomas)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-5\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klassisches_Hodgkin-Lymphom_cHL\" >Linfoma de Hodgkin cl\u00e1ssico (cHL)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-6\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Nodulares_Lymphozyten-dominantes_HL_NLPHL\" >LH nodular com predom\u00ednio de linf\u00f3citos (NLPHL)<\/a><\/li><\/ul><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-7\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Non-Hodgkin-Lymphome_NHL_ca_85-90\" >Linfoma n\u00e3o-Hodgkin (LNH, aprox. 85-90%)<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-8\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#B-Zell-Lymphome_80_aller_NHL\" >Linfomas de c\u00e9lulas B (80% de todos os LNH)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-9\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Indolente_niedrig-maligne_B-Zell-Lymphome\" >Linfomas de c\u00e9lulas B indolentes (pouco malignos):<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-10\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Aggressive_B-Zell-Lymphome\" >Linfomas agressivos de c\u00e9lulas B:<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-11\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#GrauzonenGrenzfalle\" >\u00c1reas cinzentas\/casos-limite:<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-12\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Spezielle_extranoduale_Lymphome\" >Linfomas extranodais especializados:<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-13\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#T-Zell-_und_NK-Zell-Lymphome_20_aller_NHL\" >Linfomas de c\u00e9lulas T e de c\u00e9lulas NK (20% de todos os LNH)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-14\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Periphere_T-Zell-Lymphome_PTCL\" >Linfomas perif\u00e9ricos de c\u00e9lulas T (PTCL):<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-15\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Kutane_T-Zell-Lymphome\" >Linfomas cut\u00e2neos de c\u00e9lulas T:<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-16\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Lymphoblastische_Lymphome\" >Linfomas linfobl\u00e1sticos:<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-17\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#NK-Zell-Lymphome\" >Linfomas de c\u00e9lulas NK:<\/a><\/li><\/ul><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-18\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Hodgkin-Lymphom_%E2%80%93_Verwandte_Erkrankungen\" >Linfoma de Hodgkin \u2013 Doen\u00e7as Relacionadas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-19\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Immunproliferative_Erkrankungen_Grenzfalle\" >Doen\u00e7as imunoproliferativas e casos-limite<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-20\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Epidemiologische_Ubersicht\" >Panorama epidemiol\u00f3gico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-21\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klassifikation_nach_Biologie_Prognose\" >Classifica\u00e7\u00e3o de acordo com a biologia (progn\u00f3stico)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-22\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differentielle_Darstellung_%E2%80%93_Non-Hodgkin-Lymphome\" >Representa\u00e7\u00e3o diferencial \u2013 Linfomas n\u00e3o-Hodgkin<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-23\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Follikulares_Lymphom_FL\" >Linfoma folicular (FL)<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-24\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Lymphoplasmozytisches_Lymphom_%E2%80%93_Waldenstrom-Makroglobulinamie\" >Linfoma linfoplasmocit\u00e1rio - Macroglobulinemia de Waldenstr\u00f6m<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-25\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisch-morphologische_Merkmale\" >Carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-26\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-27\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methoden\" >M\u00e9todos de diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-28\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-29\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-30\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Kleines_lymphozytische_Leukamie_Lymphom_CLLSLL\" >Leucemia linfoc\u00edtica pequena \/ linfoma (CLL\/SLL)<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-31\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Merkmale\" >Carater\u00edsticas cl\u00ednicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-32\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-2\" >Diagn\u00f3stico diferencial<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-33\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Kriterien_nach_IWCLL\" >Crit\u00e9rios de diagn\u00f3stico (de acordo com IWCLL)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-34\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnosen\" >Diagn\u00f3sticos diferenciais<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-35\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methoden-2\" >M\u00e9todos de diagn\u00f3stico<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-36\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-2\" >Previs\u00e3o<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-37\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-2\" >Terapia<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-38\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Indikation_zur_Therapie_nach_iwCLLOnkopedia\" >Indica\u00e7\u00e3o para a terap\u00eautica (de acordo com a iwCLL\/Onkopedia)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-39\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Behandlungsoptionen\" >Op\u00e7\u00f5es de tratamento<\/a><\/li><\/ul><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-40\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Marginalzonen-Lymphome\" >Linfomas da zona marginal<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-41\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Extranodales_Marginalzonen-Lymphom_MALT-Lymphom\" >Linfoma extranodal da zona marginal (linfoma MALT)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-42\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-3\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-43\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnosemethodik\" >Metodologia de diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-44\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie_und_Prognose\" >Terapia e progn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-45\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Nodales_Marginalzonen-Lymphom_nMZL\" >Linfoma da zona marginal nodal (nMZL)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-46\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Merkmale-2\" >Carater\u00edsticas cl\u00ednicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-47\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzierung_vom_splenischen_und_extranodalen_MZL\" >Diferencia\u00e7\u00e3o entre MZL espl\u00e9nico e extranodal<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-48\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzierung_von_anderen_indolenten_B-Zell-Lymphomen\" >Diferencia\u00e7\u00e3o de outros linfomas indolentes de c\u00e9lulas B<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-49\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnosemethodik-2\" >Metodologia de diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-50\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-3\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-51\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Splenisches_Marginalzonen-Lymphom_SMZL\" >Linfoma da zona marginal espl\u00e9nica (SMZL)<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-52\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Merkmale-3\" >Carater\u00edsticas cl\u00ednicas<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-53\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Zytomorphologie\" >Citomorfologia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-54\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Histologie\" >Histologia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-55\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Immunphanotyp\" >Imunofen\u00f3tipo<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-56\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Zytogenetik_und_molekulare_Marker\" >Citogen\u00e9tica e marcadores moleculares<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-57\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-4\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-58\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnosemethodik-3\" >Metodologia de diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-59\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie_und_Prognose-2\" >Terapia e progn\u00f3stico<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-60\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Primar_kutane_Lymphome_CL\" >Linfomas cut\u00e2neos prim\u00e1rios (LC)<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-61\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisch-morphologische_Merkmale-2\" >Carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-62\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnose\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-63\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methoden-3\" >M\u00e9todos de diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-64\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-4\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-65\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-3\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-66\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Primar_duodenales_B-Zell-Lymphom_MALT-Typ\" >Linfoma duodenal prim\u00e1rio de c\u00e9lulas B (tipo MALT)<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-67\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Merkmale-4\" >Carater\u00edsticas cl\u00ednicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-68\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-5\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-69\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methoden-4\" >M\u00e9todos de diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-70\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-5\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-71\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-4\" >Previs\u00e3o<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-72\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisch-morphologische_Merkmale-3\" >Carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-73\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diffus_Groszelliges_B-Zell-Lymphom_DLBCL\" >Linfoma difuso de grandes c\u00e9lulas B (DLBCL)<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-74\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Molekulare_Subtypen_Cell_of_Origin_COO\" >Subtipos moleculares (c\u00e9lula de origem, COO)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-75\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Merkmale-5\" >Carater\u00edsticas cl\u00ednicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-76\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostische_Abgrenzung\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-77\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Kriterien\" >Crit\u00e9rios de diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-78\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie_und_Prognose-3\" >Terapia e progn\u00f3stico<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-79\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Primar_mediastinales_B-Zell-Lymphom_pMBCL\" >Linfoma prim\u00e1rio de c\u00e9lulas B do mediastino (pMBCL)<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-80\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Prasentation\" >Apresenta\u00e7\u00e3o cl\u00ednica<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-81\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Pathogenese_und_Diagnostik\" >Patog\u00e9nese e diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-82\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie_und_Prognose-4\" >Terapia e progn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-83\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-6\" >Diagn\u00f3stico diferencial<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-84\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Burkitt-Lymphom_BL\" >Linfoma de Burkitt (BL)<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-85\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Merkmale-6\" >Carater\u00edsticas cl\u00ednicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-86\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-7\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-87\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methoden-5\" >M\u00e9todos de diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-88\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-6\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-89\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-5\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-90\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Lymphoblastisches_Lymphom_BL\" >Linfoma linfobl\u00e1stico (BL)<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-91\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisch-morphologische_Merkmale-4\" >Carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-92\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-8\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-93\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methoden-6\" >M\u00e9todos de diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-94\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-7\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-95\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-6\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-96\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Primar_kutanes_diffus_groszelliges_B-Zell-Lymphom_Beintyp_DLBCL_LT\" >Linfoma cut\u00e2neo prim\u00e1rio difuso de grandes c\u00e9lulas B, tipo perna (DLBCL, LT)<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-97\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Merkmale-7\" >Carater\u00edsticas cl\u00ednicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-98\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisch-morphologische_Merkmale-5\" >Carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-99\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-9\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-100\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methoden-7\" >M\u00e9todos de diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-101\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-8\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-102\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-7\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-103\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#GrauzonenGrenzfalle-2\" >\u00c1reas cinzentas\/casos-limite<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-104\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diffus_groszelliges_B-Zell-Lymphom_NOS_DLBCL_NOS_und_Burkitt-Lymphom_BL\" >Linfoma difuso de grandes c\u00e9lulas B, n\u00e3o especificado (DLBCL, NOS) e Linfoma de Burkitt (LB)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-105\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_und_morphologisches_Bild\" >Quadro cl\u00ednico e morfol\u00f3gico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-106\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_Methodik\" >Diagn\u00f3stico diferencial e metodologia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-107\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-9\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-108\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-8\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-109\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Spezielle_extranoduale_Lymphome-2\" >Linfomas extranodais especiais<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-110\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Hepatosplenisches_Lymphom_HSTL\" >Linfoma hepatoespl\u00e9nico (LHSE)<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-111\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Merkmale-8\" >Carater\u00edsticas cl\u00ednicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-112\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-10\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-113\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methoden-8\" >M\u00e9todos de diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-114\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie_und_Prognose-5\" >Terapia e progn\u00f3stico<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-115\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Intravaszulares_groszelliges_B-Zell-Lymphom\" >Linfoma intravascular de grandes c\u00e9lulas B<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-116\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Merkmale-9\" >Carater\u00edsticas cl\u00ednicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-117\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostik\" >Diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-118\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-11\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-119\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie_und_Prognose-6\" >Terapia e progn\u00f3stico<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-120\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Primar_Effusions-Lymphom_PEL\" >Linfoma de efus\u00e3o prim\u00e1ria (PEL)<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-121\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-12\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-122\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_und_immunophanotypische_Unterscheidung\" >Diferencia\u00e7\u00e3o cl\u00ednica e imunofenot\u00edpica<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-123\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#HHV8-Assoziiiertes_Lymphom\" >Linfoma associado ao HHV8<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-124\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-13\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-125\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_und_histologische_Merkmale\" >Carater\u00edsticas cl\u00ednicas e histol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-126\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_zu_anderen_Lymphomen\" >Diagn\u00f3stico diferencial com outros linfomas<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-127\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#T-Zell-_und_NK-Zell-Lymphome\" >Linfomas de c\u00e9lulas T e de c\u00e9lulas NK<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-128\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Peripheres_T-Zell-Lymphom_PTCL-NOS\" >Linfoma perif\u00e9rico de c\u00e9lulas T (PTCL-NOS)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-129\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisch-morphologische_Merkmale-6\" >Carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-130\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-14\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-131\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methoden-9\" >M\u00e9todos de diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-132\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-10\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-133\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-9\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-134\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Angioimmunoblastisches_T-Zell-Lymphom_AITL\" >Linfoma angioimunobl\u00e1stico de c\u00e9lulas T (AITL)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-135\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Merkmale_und_morphologische_Zeichen\" >Carater\u00edsticas cl\u00ednicas e sinais morfol\u00f3gicos<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-136\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnose-2\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-137\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methodik\" >Metodologia de diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-138\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-11\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-139\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-10\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-140\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Follikulares_T-Zell-Lymphom_PTFCL\" >Linfoma folicular de c\u00e9lulas T (PTFCL)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-141\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisch-morphologische_Merkmale-7\" >Carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-142\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik\" >Diagn\u00f3stico diferencial e metodologia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-143\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-12\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-144\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-11\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-145\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Hepatosplenisches_T-Zell-Lymphom_%CE%B3%CE%B4-Typ\" >Linfoma hepatoespl\u00e9nico de c\u00e9lulas T (tipo \u03b3\u03b4)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-146\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_und_klinisch-morphologische_Merkmale\" >Carater\u00edsticas cl\u00ednicas e cl\u00ednico-morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-147\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik-2\" >Diagn\u00f3stico diferencial e metodologia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-148\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-13\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-149\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-12\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-150\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Enteropathie-assoziiertes_T-Zell-Lymphom_EATL\" >Linfoma de c\u00e9lulas T associado a enteropatia (EATL)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-151\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild\" >Imagem cl\u00ednica<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-152\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Morphologische_Merkmale\" >Carater\u00edsticas morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-153\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-15\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-154\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methodik-2\" >Metodologia de diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-155\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-14\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-156\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-13\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-157\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Anaplastisches_groszelliges_Lymphom_ALCL\" >Linfoma anapl\u00e1sico de grandes c\u00e9lulas (ALCL)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-158\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild-2\" >Imagem cl\u00ednica<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-159\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Morphologie\" >Morfologia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-160\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-16\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-161\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-15\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-162\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-14\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-163\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Mycosis_fungoides\" >Micose fung\u00f3ide<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-164\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_klinisch-morphologische_Merkmale\" >Quadro cl\u00ednico e carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-165\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik-3\" >Diagn\u00f3stico diferencial e metodologia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-166\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-16\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-167\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-15\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-168\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Sezary-Syndrom\" >S\u00edndrome de S\u00e9zary<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-169\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild-3\" >Imagem cl\u00ednica<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-170\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Morphologie-2\" >Morfologia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-171\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-17\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-172\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methodik-3\" >Metodologia de diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-173\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-17\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-174\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-16\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-175\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Primar_kutanes_anaplastisches_groszelliges_CD30-positives_Lymphom_cALCL\" >Linfoma cut\u00e2neo prim\u00e1rio anapl\u00e1sico de grandes c\u00e9lulas CD30-positivo (cALCL)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-176\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_und_morphologisches_Bild-2\" >Quadro cl\u00ednico e morfol\u00f3gico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-177\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik-4\" >Diagn\u00f3stico diferencial e metodologia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-178\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-18\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-179\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-17\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-180\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Kutanes_Marginalzonen-Lymphom\" >Linfoma cut\u00e2neo da zona marginal<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-181\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_klinisch-morphologische_Merkmale-2\" >Quadro cl\u00ednico e carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-182\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik-5\" >Diagn\u00f3stico diferencial e metodologia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-183\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostik-2\" >Diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-184\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-19\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-185\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-18\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-186\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Kutanes_Lymphom_mit_korniger_Mittelfingertatowierung\" >Linfoma cut\u00e2neo com tatuagem granular do dedo m\u00e9dio<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-187\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_klinisch-morphologische_Merkmale-3\" >Quadro cl\u00ednico e carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-188\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnose_und_Diagnostik\" >Diagn\u00f3stico diferencial e diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-189\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostikmethodik\" >Metodologia de diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-190\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-20\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-191\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-19\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-192\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#B-lymphoblastisches_LymphomLeukamie_B-ALL\" >Linfoma\/leucemia linfobl\u00e1stica B (B-ALL)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-193\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_klinisch-morphologische_Merkmale-4\" >Quadro cl\u00ednico e carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-194\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-18\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-195\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostikmethoden\" >M\u00e9todos de diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-196\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-21\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-197\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-20\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-198\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#T-lymphoblastisches_LymphomLeukamie_T-ALL\" >Linfoma\/leucemia linfobl\u00e1stica T (T-ALL)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-199\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisch-morphologische_Merkmale-8\" >Carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-200\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-19\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-201\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostik-3\" >Diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-202\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-22\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-203\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-21\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-204\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#NK-Zell-Lymphome-2\" >Linfomas de c\u00e9lulas NK<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-205\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Extranodales_NK-Zell-Lymphom\" >Linfoma extranodal de c\u00e9lulas NK<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-206\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_morphologische_Merkmale\" >Quadro cl\u00ednico e carater\u00edsticas morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-207\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-20\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-208\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostikmethodik-2\" >Metodologia de diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-209\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-23\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-210\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-22\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-211\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Agressive_NK-Zell-Leukamie_ANKL\" >Leucemia agressiva de c\u00e9lulas NK (ANKL)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-212\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_und_morphologisches_Bild-3\" >Quadro cl\u00ednico e morfol\u00f3gico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-213\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik-6\" >Diagn\u00f3stico diferencial e metodologia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-214\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnosen-2\" >Diagn\u00f3sticos diferenciais<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-215\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methodik-4\" >Metodologia de diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-216\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-24\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-217\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-23\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-218\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Chronische_NK-Zell-Leukamie\" >Leucemia cr\u00f3nica de c\u00e9lulas NK<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-219\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_klinisch-morphologische_Merkmale-5\" >Quadro cl\u00ednico e carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-220\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik-7\" >Diagn\u00f3stico diferencial e metodologia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-221\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-25\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-222\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-24\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-223\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Hodgkin-Lymphom_%E2%80%93_Verwandte_Erkrankungen-2\" >Linfoma de Hodgkin \u2013 Doen\u00e7as Relacionadas<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-224\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Nodulares_lymphozytenpradominantes_Hodgkin-Lymphom_NLPHL\" >Linfoma de Hodgkin nodular com predomin\u00e2ncia de linf\u00f3citos (NLPHL)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-225\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_und_morphologisches_Bild-4\" >Quadro cl\u00ednico e morfol\u00f3gico<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-226\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik-8\" >Diagn\u00f3stico diferencial e metodologia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-227\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostik-4\" >Diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-228\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-26\" >Terapia<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-229\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-25\" >Previs\u00e3o<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-230\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#EBV-positives_diffuses_groszelliges_B-Zell-Lymphom_PTLD\" >Linfoma difuso de grandes c\u00e9lulas B (PTLD) EBV-positivo<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-231\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_und_morphologisches_Bild-5\" >Quadro cl\u00ednico e morfol\u00f3gico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-232\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-21\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-233\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostik-5\" >Diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-234\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-27\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-235\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-26\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-236\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Immunproliferative_Erkrankungen_Grenzfalle-2\" >Doen\u00e7as imunoproliferativas e casos-limite<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-237\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#MALT-Lymphome\" >Linfomas MALT<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-238\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_morphologische_Merkmale-2\" >Quadro cl\u00ednico e carater\u00edsticas morfol\u00f3gicas<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-239\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_Diagnostik\" >Diagn\u00f3stico diferencial e diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-240\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-28\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-241\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#MALT-Lymphom\" >Linfoma MALT<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-242\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Posttransplantationale_lymphoproliferative_Storung_PTLD\" >Doen\u00e7a linfoproliferativa p\u00f3s-transplante (PTLD)<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-243\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-27\" >Previs\u00e3o<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-244\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#MALT-Lymphom-2\" >Linfoma MALT<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-245\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#PTLD\" >PTLD<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-246\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Zusammenfassung\" >Resumo<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-247\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Lymphomatoide_Granulomatose\" >Granulomatose linfomat\u00f3ide<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-248\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_klinisch-morphologische_Merkmale-6\" >Quadro cl\u00ednico e carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-249\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik-9\" >Diagn\u00f3stico diferencial e metodologia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-250\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-29\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-251\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-28\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-252\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Granulomatose_mit_organerhaltender_Vaskulitis_GANZL\" >Granulomatose com vasculite preservadora de \u00f3rg\u00e3os (GANZL)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-253\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_klinisch-morphologische_Merkmale-7\" >Quadro cl\u00ednico e carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-254\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnose_und_-methodik\" >Diagn\u00f3stico diferencial e metodologia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-255\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-30\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-256\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-29\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-257\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#EBV-assoziierte_B-Zell-Lymphoproliferationen\" >Linfoprolifera\u00e7\u00f5es de c\u00e9lulas B associadas ao EBV<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-258\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_morphologische_Merkmale-3\" >Quadro cl\u00ednico e carater\u00edsticas morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-259\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_Methodik-2\" >Diagn\u00f3stico diferencial e metodologia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-260\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-31\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-261\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-30\" >Previs\u00e3o<\/a><ul class='ez-toc-list-level-5' ><li class='ez-toc-heading-level-5'><a class=\"ez-toc-link ez-toc-heading-262\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#PTLD-2\" >PTLD<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-5'><a class=\"ez-toc-link ez-toc-heading-263\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#EBV_DLBCL_des_alteren_Menschen\" >EBV+ DLBCL em idosos<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-5'><a class=\"ez-toc-link ez-toc-heading-264\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Primar_kutanes_DLBCL_untere_Extremitat\" >DLBCL cut\u00e2neo prim\u00e1rio, extremidade inferior<\/a><\/li><\/ul><\/li><\/ul><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-265\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Hodgkin-Lymphom\" >Linfoma de Hodgkin<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-266\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klassisches_Hodgkin-Lymphom_nodulare_Sklerose_cHL_NS\" >Linfoma de Hodgkin cl\u00e1ssico, esclerose nodular (cHL, NS)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-267\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild-4\" >Imagem cl\u00ednica<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-268\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisch-morphologische_Merkmale-9\" >Carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-269\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-22\" >Diagn\u00f3stico diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-270\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostik-6\" >Diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-271\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-32\" >Terapia<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-272\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Stadienadaptierte_Therapie\" >Terapia adaptada \u00e0 fase<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-273\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-31\" >Previs\u00e3o<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-274\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klassisches_Hodgkin-Lymphom_cHL_%E2%80%93_gemischte_Zellularitat_MC\" >Linfoma de Hodgkin cl\u00e1ssico (cHL) - celularidade mista (MC)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-275\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_morphologische_Merkmale-4\" >Quadro cl\u00ednico e carater\u00edsticas morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-276\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnose_und_-methodik-2\" >Diagn\u00f3stico diferencial e metodologia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-277\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie_und_Prognose-7\" >Terapia e progn\u00f3stico<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-278\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klassisches_Hodgkin-Lymphom_%E2%80%93_lymphozytenreicher_Typ_cHL_LR\" >Linfoma de Hodgkin cl\u00e1ssico - tipo rico em linf\u00f3citos (cHL, LR)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-279\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_morphologische_Merkmale-5\" >Quadro cl\u00ednico e carater\u00edsticas morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-280\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik-10\" >Diagn\u00f3stico diferencial e metodologia<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-281\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-33\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-282\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-32\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-283\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klassisches_lymphozytenarmes_Hodgkin-Lymphom_cHL\" >Linfoma de Hodgkin cl\u00e1ssico pobre em linf\u00f3citos (cHL)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-284\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_morphologische_Merkmale-6\" >Quadro cl\u00ednico e carater\u00edsticas morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-285\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik-11\" >Diagn\u00f3stico diferencial e metodologia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-286\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostik-7\" >Diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-287\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-34\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-288\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-33\" >Previs\u00e3o<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-289\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Nodulares_lymphozytenpradominantes_Hodgkin-Lymphom_NLPHL-2\" >Linfoma de Hodgkin nodular com predomin\u00e2ncia de linf\u00f3citos (NLPHL)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-290\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_morphologische_Merkmale-7\" >Quadro cl\u00ednico e carater\u00edsticas morfol\u00f3gicas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-291\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnosen_und_Differenzialmethodik\" >Diagn\u00f3sticos diferenciais e metodologia diferencial<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-292\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostik-8\" >Diagn\u00f3stico<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-293\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-35\" >Terapia<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-294\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-34\" >Previs\u00e3o<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-295\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Standard-Therapeutika_Chemo\" >Terap\u00eautica padr\u00e3o (quimioterapia)<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-296\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Hodgkin-Lymphom-2\" >Linfoma de Hodgkin<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-297\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#ABVD\" >ABVD<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-298\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#BEACOPP\" >BEACOPP<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-299\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#BrECADD\" >BrECADD<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-300\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Non-Hodgkin-Lymphom_NHL\" >Linfoma n\u00e3o-Hodgkin (LNH)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-301\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#CHOP\" >CHOP<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-302\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#R-Bendamustin\" >R-Bendamustina<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-303\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#R-DHAP_R-ICE\" >R-DHAP \/ R-ICE<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-304\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#R-ICE\" >R-ICE<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-305\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#CVP\" >CVP<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-306\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Spezielle_Formen\" >Moldes especiais<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-307\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Standard-Therapeutika_%E2%80%93_Signalwege\" >Terap\u00eautica padr\u00e3o - vias de sinaliza\u00e7\u00e3o<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-308\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Bendamustin\" >Bendamustina<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-309\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Bleomycin\" >Bleomicina<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-310\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Cisplatin_Carboplatin\" >Cisplatina \/ Carboplatina<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-311\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Cyclophosphamid\" >Ciclofosfamida<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-312\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Cytarabin_Ara-C\" >Citarabina (Ara-C)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-313\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Dacarbacin\" >Dacarbacina<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-314\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Dexamethason\" >Dexametasona<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-315\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Doxorubicin\" >Doxorrubicina<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-316\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Etoposid\" >Etoposido<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-317\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Glukokortikoide_Prednison_Prednisolon\" >Glucocortic\u00f3ides (prednisona \/ prednisolona)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-318\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Ifosfamid\" >Ifosfamida<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-319\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Procarbazin\" >Procarbazina<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-320\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Rituximab\" >Rituximab<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-321\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Vincristin_Vinblastin\" >Vincristina \/ vinblastina<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-322\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Phyto-Therapiemoglichkeiten\" >Op\u00e7\u00f5es de fitoterapia<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-323\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Huaier-Pilz_Trametes_robiniophila_Murr\" >Cogumelo de Huaier (Trametes robiniophila Murr.)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-324\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben\" >Refer\u00eancias<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-325\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Reishi_Ganoderma_lucidum\" >Reishi (Ganoderma lucidum)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-326\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-2\" >Refer\u00eancias<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-327\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Shiitake_Lentinula_edodes\" >Shiitake (Lentinula edodes)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-328\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-3\" >Refer\u00eancias<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-329\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Maitake_Grifola_frondosa\" >Maitake (Grifola frondosa)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-330\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-4\" >Refer\u00eancias<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-331\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Coriolus_Trametes_versicolor_Polyporus_umbellatus\" >Coriolus (Trametes versicolor \/ Polyporus umbellatus)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-332\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-5\" >Refer\u00eancias<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-333\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Berberin_Berberis_vulgaris\" >Berberina (Berberis vulgaris)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-334\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-6\" >Refer\u00eancias<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-335\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Echinacea_Sonnenhut\" >Equin\u00e1cea (flor de cone)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-336\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-7\" >Refer\u00eancias<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-337\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Kurkuma_Curcumin\" >A\u00e7afr\u00e3o-da-terra (curcumina)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-338\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-8\" >Refer\u00eancias<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-339\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Ingwer_Gingerole\" >Gengibre (ginger\u00f3is)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-340\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-9\" >Refer\u00eancias<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-341\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Zitrusfruchte_Quercetin\" >Citrinos e quercetina<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-342\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-10\" >Refer\u00eancias<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-343\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Schwarzkummelol_Nigella_sativa\" >\u00d3leo de sementes de cominho preto (Nigella sativa)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-344\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-11\" >Refer\u00eancias<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-345\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Ginseng_Panax_ginseng\" >Ginseng (Panax ginseng)<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-346\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-12\" >Refer\u00eancias<\/a><\/li><\/ul><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-347\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Phyto-Therapeutika_%E2%80%93_Signalwege\" >Fito-terap\u00eautica - vias de sinaliza\u00e7\u00e3o<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-348\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Huaier_Trametes_robiniophila_Murr\" >Huaier (Trametes robiniophila Murr.)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-349\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Reishi_Ganoderma_lucidum-2\" >Reishi (Ganoderma lucidum)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-350\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Shiitake_Lentinula_edodes-2\" >Shiitake (Lentinula edodes)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-351\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Maitake_Grifola_frondosa-2\" >Maitake (Grifola frondosa)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-352\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Coriolus_Trametes_versicolor_Polyporus_umbellatus-2\" >Coriolus (Trametes versicolor \/ Polyporus umbellatus)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-353\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Berberin_Berberis_vulgaris-2\" >Berberina (Berberis vulgaris)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-354\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Echinacea_Sonnenhut-2\" >Equin\u00e1cea (flor de cone)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-355\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Kurkuma_Curcumin-2\" >A\u00e7afr\u00e3o-da-terra (curcumina)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-356\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Ingwer_Gingerole-2\" >Gengibre (ginger\u00f3is)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-357\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Zitrusfruchte_Quercetin-2\" >Citrinos e quercetina<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-358\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Schwarzkummelol_Nigella_sativa-2\" >\u00d3leo de sementes de cominho preto (Nigella sativa)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-359\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Ginseng_Panax_ginseng-2\" >Ginseng (Panax ginseng)<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-360\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Rituximab_%E2%80%93_die_Entwicklungsgeschichte\" >Rituximab - a hist\u00f3ria do desenvolvimento<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-361\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#1975_%E2%80%93_Entwicklung_der_Hybridoma-Technologie\" >1975 - Desenvolvimento da tecnologia dos hibridomas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-362\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Wie_konnen_Zellen_unsterblich_sein\" >Como \u00e9 que as c\u00e9lulas podem ser imortais?<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-363\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Plasmozytom_bei_Mausen_%E2%80%93_die_ursprungliche_Quelle\" >Plasmocitoma em ratos - a fonte original<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-364\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Die_erste_gangige_Zelllinie_%E2%80%93_SP20\" >A primeira linha celular comum - SP2\/0<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-365\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Warum_sind_Myelomzellen_unsterblich\" >Porque \u00e9 que as c\u00e9lulas do mieloma s\u00e3o imortais?<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-366\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Normale_Zellen_%E2%80%93_Das_Hayflick-Limit\" >C\u00e9lulas normais - O limite de Hayflick<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-367\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Krebszellen_sind_erfinderisch_%E2%80%93_aktivieren_Telomerase\" >As c\u00e9lulas cancerosas s\u00e3o inventivas - activam a telomerase<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-368\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Warum_Telomerase\" >Porqu\u00ea a telomerase?<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-369\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#TP53-Mutation_%E2%80%93_das_andere_Puzzle-Teil\" >Muta\u00e7\u00e3o TP53 - a outra pe\u00e7a do puzzle<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-370\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Wie_Myelomzellen_unsterblich_wurden\" >Como \u00e9 que as c\u00e9lulas do mieloma se tornaram imortais<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-371\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Die_erste_SP20_Hybridoma-Zelle\" >A primeira c\u00e9lula de hibridoma SP2\/0<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-372\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Warum_keine_normale_B-Zellen\" >Porqu\u00ea a aus\u00eancia de c\u00e9lulas B normais?<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-373\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Die_Fusion_%E2%80%93_der_Hybridoma-Prozess\" >A fus\u00e3o - o processo de hibridoma<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-374\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Warum_Zellen_eines_Myeloms_und_nicht_anderer_Tumore\" >Porqu\u00ea c\u00e9lulas de mieloma e n\u00e3o de outros tumores?<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-375\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Das_Paradoxe_%E2%80%93_Krebszellen_als_Mittel_gegen_Krebs\" >O paradoxo - as c\u00e9lulas cancerosas como rem\u00e9dio para o cancro<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-376\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Neuere_Alternativen\" >Novas alternativas<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-377\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Zusammenfassung-2\" >Resumo<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-378\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#1980_%E2%80%93_Entdeckung_des_Oberflachenproteins_CD20\" >1980 - Descoberta da prote\u00edna de superf\u00edcie CD20<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-379\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Erstes_Experiment\" >Primeira experi\u00eancia<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-380\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Das_chimare_Antikorper-Problem\" >O problema dos anticorpos quim\u00e9ricos<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-381\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#1990-1992_%E2%80%93_Rituximab-Entwicklung\" >1990-1992 - Desenvolvimento do Rituximab<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-382\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Das_IDEC-Team\" >A equipa do IDEC<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-383\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Entwicklung\" >Desenvolvimento<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-384\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#1993-1997_%E2%80%93_Klinische_Tests\" >1993-1997 - Ensaios cl\u00ednicos<\/a><ul class='ez-toc-list-level-4' ><li class='ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-385\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#1994_%E2%80%93_Phase-I-Studie\" >1994 - Estudo de fase I<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-386\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#1997_%E2%80%93_Phase-II-Studie\" >1997 - Estudo de fase II<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-4'><a class=\"ez-toc-link ez-toc-heading-387\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#1997_%E2%80%93_FDA-Zulassung_November\" >1997 - Aprova\u00e7\u00e3o da FDA (novembro)<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-388\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Warum_genau_dieser_Maus-Antikorper\" >Porqu\u00ea exatamente este anticorpo de rato?<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-389\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Seit_1997\" >Desde 1997<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-390\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Dosierungsempfehlungen\" >Recomenda\u00e7\u00f5es de dosagem<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-391\" href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Fur_ABC-DLBCL\" >Para DLBCL-ABC<\/a><\/li><\/ul><\/li><\/ul><\/nav><\/div>\n\n<p class=\"wp-block-paragraph\">Existem dezenas de tipos de linfoma. Nem todos os tipos respondem a todos os tratamentos, e um tratamento pode at\u00e9 ser contraproducente para um determinado tipo de linfoma.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Por um lado, esta vis\u00e3o geral destina-se a apoiar um diagn\u00f3stico s\u00f3lido e, por outro lado, tamb\u00e9m se destina a discutir op\u00e7\u00f5es terap\u00eauticas espec\u00edficas - \u00e0 base de plantas - que s\u00e3o adequadas em fun\u00e7\u00e3o do tipo e subtipo de linfoma.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Nos casos em que existem estudos cl\u00ednicos sobre uma forma de terapia adjuvante, estes s\u00e3o referidos no texto. Os resultados in vitro s\u00e3o abordagens teoricamente poss\u00edveis ou baseiam-se em testes laboratoriais que n\u00e3o s\u00e3o necessariamente transfer\u00edveis diretamente para os seres humanos: O que funciona na placa de Petri, na qual a subst\u00e2ncia ativa entra em contacto direto com um agente patog\u00e9nico, pode tamb\u00e9m conduzir a resultados diferentes devido a uma biodisponibilidade diferente no organismo.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">No entanto, uma vez que a medicina n\u00e3o est\u00e1, em geral, primariamente interessada em subst\u00e2ncias activas puramente \u00e0 base de plantas e na sua investiga\u00e7\u00e3o exaustiva no contexto de estudos aleat\u00f3rios, duplamente cegos e revistos por pares - dependentes de financiamento adequado - na aus\u00eancia de um poss\u00edvel registo de patentes, a abordagem te\u00f3rica constitui uma oportunidade para os m\u00e9dicos interessados oferecerem aos seus pacientes alternativas \u00e0 base de plantas baseadas em provas, que, por conseguinte - comprovadamente - t\u00eam a sua justifica\u00e7\u00e3o como adjuvantes.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u00c9 dada uma apresenta\u00e7\u00e3o diferenciada para cada tipo de linfoma, que inclui os seguintes aspectos:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Carater\u00edsticas cl\u00ednicas<\/li>\n\n\n\n<li>Diagn\u00f3stico diferencial<\/li>\n\n\n\n<li>M\u00e9todos de diagn\u00f3stico<\/li>\n\n\n\n<li>Terap\u00eautica (padr\u00e3o) e progn\u00f3stico<\/li>\n\n\n\n<li>Op\u00e7\u00e3o(\u00f5es) terap\u00eautica(s) alternativa(s)<\/li>\n<\/ul>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\">Todas as informa\u00e7\u00f5es aqui fornecidas foram cuidadosamente pesquisadas de acordo com os nossos conhecimentos actuais, mas n\u00e3o substituem uma consulta e um acordo com um especialista.<\/p>\n<\/blockquote>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Wie_entstehen_Lymphom-Erkrankungen\"><\/span>Como \u00e9 que os linfomas se desenvolvem?<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Os linfomas s\u00e3o causados por uma altera\u00e7\u00e3o maligna dos linf\u00f3citos<\/strong>, os gl\u00f3bulos brancos do sistema imunit\u00e1rio. Estas c\u00e9lulas, que normalmente combatem as infec\u00e7\u00f5es, s\u00e3o alteradas por&nbsp;<strong>Processos aleat\u00f3rios no genoma<\/strong>, normalmente devido a altera\u00e7\u00f5es gen\u00e9ticas, como transloca\u00e7\u00f5es ou muta\u00e7\u00f5es cromoss\u00f3micas. Estas altera\u00e7\u00f5es levam as c\u00e9lulas a&nbsp;<strong>multiplicar-se de forma incontrol\u00e1vel<\/strong>, e j\u00e1 n\u00e3o morrem e deslocam o tecido saud\u00e1vel.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Embora a causa exacta da maioria dos linfomas n\u00e3o seja totalmente compreendida&nbsp;<strong>alguns factores desempenham um papel importante<\/strong>, que aumentam o risco de doen\u00e7a:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Idade<\/strong>O risco aumenta com a idade, especialmente ap\u00f3s os 60 anos.&nbsp;<\/li>\n\n\n\n<li><strong>Sistema imunit\u00e1rio enfraquecido<\/strong>Os linfomas ocorrem mais frequentemente em pessoas com imunossupress\u00e3o (por exemplo, ap\u00f3s transplante de \u00f3rg\u00e3os, VIH ou doen\u00e7as auto-imunes).&nbsp;<\/li>\n\n\n\n<li><strong>Infec\u00e7\u00f5es<\/strong>Alguns v\u00edrus (como o v\u00edrus Epstein-Barr) ou bact\u00e9rias (como&nbsp;<em>Helicobacter pylori<\/em>) pode favorecer certos tipos de linfoma.&nbsp;<\/li>\n\n\n\n<li><strong>Factores ambientais<\/strong>A radia\u00e7\u00e3o (por exemplo, raios X, radioatividade) e os poluentes qu\u00edmicos (por exemplo, pesticidas, benzeno) podem promover o desenvolvimento.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Einleitung\"><\/span>Introdu\u00e7\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">As doen\u00e7as do linfoma s\u00e3o <strong>n\u00e3o herd\u00e1vel<\/strong>, <strong>n\u00e3o contagioso<\/strong>, <strong>raro<\/strong>, Ainda mais raros s\u00e3o, no entanto, os bons progn\u00f3sticos no que respeita a uma recupera\u00e7\u00e3o com poucas complica\u00e7\u00f5es.<br>Mesmo que o progn\u00f3stico seja inicialmente muito favor\u00e1vel, uma radioterapia bem sucedida pode causar danos que podem n\u00e3o se tornar aparentes at\u00e9 anos ou mesmo uma d\u00e9cada mais tarde.<br>Mesmo os transplantes de c\u00e9lulas estaminais adequados e terapeuticamente \u00fateis (bem como os transplantes de \u00f3rg\u00e3os) podem causar linfomas em doentes imunocomprometidos nos primeiros anos, ou numa segunda tentativa ap\u00f3s cerca de 5 a 10 anos.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Embora os agentes quimioter\u00e1picos ataquem mais ou menos \u201eespecificamente\u201c as c\u00e9lulas-alvo, tamb\u00e9m devem atuar sistemicamente, ou seja, em todo o organismo, devido \u00e0 infe\u00e7\u00e3o sist\u00e9mica, os efeitos secund\u00e1rios conhecidos da quimioterapia s\u00e3o sempre relevantes para o doente em termos dos seus efeitos.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Por isso, \u00e9 importante fazer tudo o que for poss\u00edvel para fortalecer o organismo em rela\u00e7\u00e3o aos inevit\u00e1veis efeitos nocivos sist\u00e9micos da quimioterapia e da radioterapia.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Isto pode ser conseguido atrav\u00e9s de um <strong>Mudan\u00e7a de dieta<\/strong>, mas tamb\u00e9m <a href=\"#PTM\">Utiliza\u00e7\u00e3o de ingredientes activos adjuvantes \u00e0 base de plantas<\/a> que t\u00eam um efeito de refor\u00e7o imunit\u00e1rio e de regula\u00e7\u00e3o.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">UM <strong>sistema imunit\u00e1rio forte(!)<\/strong> n\u00e3o \u00e9 t\u00e3o f\u00e1cil de enganar e <strong>resiste<\/strong> a manipula\u00e7\u00e3o - indesej\u00e1vel - das medidas de quimioterapia e radioterapia <strong>Significativamente melhor<\/strong>.<br>E sim, o <strong>Com uma superf\u00edcie de cerca de 260-300 metros, o intestino representa<sup>2<\/sup> cerca de 70-80 % do sistema imunit\u00e1rio humano<\/strong>:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A maioria destas c\u00e9lulas imunit\u00e1rias est\u00e1 localizada na mucosa intestinal e forma o&nbsp;<strong>tecido linfoide associado ao intestino (GALT)<\/strong>.&nbsp;<br>\u00c9 aqui que as c\u00e9lulas imunit\u00e1rias s\u00e3o educadas, treinadas e activadas para distinguir entre subst\u00e2ncias inofensivas (como alimentos e bact\u00e9rias intestinais) e intrusos perigosos (como bact\u00e9rias ou v\u00edrus). <\/p>\n\n\n\n<p class=\"wp-block-paragraph\">No entanto, a pior estrat\u00e9gia em todos os aspectos \u00e9 a pol\u00edtica da avestruz! <strong>\u00c9 essencial respeitar exatamente os intervalos de exame<\/strong>, Isto porque os linfomas podem mudar (transformar-se) e, se o diagn\u00f3stico (de acompanhamento) n\u00e3o for efectuado ou se for efectuado demasiado tarde ou em resultado de uma terapia incorrecta, isso \u00e9 geralmente em claro preju\u00edzo para o doente.<br>Aqueles que est\u00e3o atentos e s\u00e3o proactivos t\u00eam uma clara vantagem!<\/p>\n\n\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Ubersicht_der_Lymphomarten\"><\/span>Vis\u00e3o geral dos tipos de linfoma<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Os linfomas s\u00e3o classificados de acordo com <strong>Classifica\u00e7\u00e3o da OMS<\/strong> (2022) dividem-se em dois grupos principais com v\u00e1rias subesp\u00e9cies:<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Hodgkin-Lymphom_ca_10-15_aller_Lymphome\"><\/span><strong>Linfoma de Hodgkin (aprox. 10-15% de todos os linfomas)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klassisches_Hodgkin-Lymphom_cHL\"><\/span>Linfoma de Hodgkin cl\u00e1ssico (cHL)<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"#cHL_NS\">Esclerose nodular (NL)<\/a> (60-70%) - forma mais comum<\/li>\n\n\n\n<li><a href=\"#cHL_MC\">C\u00e9lula mista (MC) <\/a>(15-20%)<\/li>\n\n\n\n<li><strong><a href=\"#cHL_LR\">Rica em linf\u00f3citos (LR)<\/a><\/strong> (5%)<\/li>\n\n\n\n<li><a href=\"#cHL\"><strong>Pobre em linf\u00f3citos<\/strong> (cHL)<\/a> (5%)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Nodulares_Lymphozyten-dominantes_HL_NLPHL\"><\/span><a href=\"#NLPHL\">LH nodular com predom\u00ednio de linf\u00f3citos (NLPHL)<\/a><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Variante mais rara com melhor progn\u00f3stico<\/li>\n<\/ul>\n\n\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Non-Hodgkin-Lymphome_NHL_ca_85-90\"><\/span><strong>N\u00e3o<strong>Linfoma de Hodgkin<\/strong><\/strong>e<strong> (NHL, aprox. 85-90%)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"B-Zell-Lymphome_80_aller_NHL\"><\/span><strong>Linfomas de c\u00e9lulas B (80% de todos os LNH)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Indolente_niedrig-maligne_B-Zell-Lymphome\"><\/span><strong>Linfomas de c\u00e9lulas B indolentes (pouco malignos):<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"#FL\"><strong>Linfoma folicular<\/strong> (FL) <\/a>- Forma indolente mais comum<\/li>\n\n\n\n<li><strong><a href=\"#LPL\">Linfoma linfoplasmocit\u00e1rio<\/a><\/strong> \/ Macroglobulinemia de Waldenstr\u00f6m<\/li>\n\n\n\n<li><a href=\"#CLL_SLL\"><strong>Leucemia linfoc\u00edtica pequena\/linfoma<\/strong> (SLL\/CLL)<\/a><\/li>\n\n\n\n<li><a href=\"#NMZL\"><strong>Linfoma da zona marginal nodal<\/strong> (NMZL)<\/a><\/li>\n\n\n\n<li><a href=\"#SMZL\"><strong>Linfoma da zona marginal espl\u00e9nica<\/strong> (SMZL)<\/a><\/li>\n\n\n\n<li><a href=\"#CL\"><strong>Linfoma cut\u00e2neo prim\u00e1rio<\/strong> (Micose fungoide\/S\u00edndrome de S\u00e9zary)<\/a><\/li>\n\n\n\n<li><a href=\"#PDBZLM\"><strong>Linfoma duodenal prim\u00e1rio de c\u00e9lulas B<\/strong> (tipo MALT)<\/a><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Aggressive_B-Zell-Lymphome\"><\/span><strong>Linfomas agressivos de c\u00e9lulas B:<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"#DLBCL\"><strong>Linfoma difuso de grandes c\u00e9lulas B<\/strong> (DLBCL)<\/a> - Forma agressiva mais comum<br>- NOS (N\u00e3o especificado de outra forma)<br>- <a href=\"#pMBCL\">DLBCL mediastinal prim\u00e1rio (pMBCL)<\/a><br>- Linfoma transformado de alto grau<\/li>\n\n\n\n<li><strong><a href=\"#BL\">Linfoma de Burkitt<\/a><\/strong> - crescimento muito agressivo e r\u00e1pido<\/li>\n\n\n\n<li><strong><a href=\"#LBL\">Linfoma linfobl\u00e1stico<\/a><\/strong><\/li>\n\n\n\n<li><a href=\"#PKDGBZL\"><strong>Linfoma cut\u00e2neo prim\u00e1rio de grandes c\u00e9lulas<\/strong> (variante centrotaximal)<\/a><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"GrauzonenGrenzfalle\"><\/span><strong>\u00c1reas cinzentas\/casos-limite:<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong><a href=\"#BLu\">Linfoma de c\u00e9lulas B, n\u00e3o classific\u00e1vel<\/a><\/strong> (entre DLBCL e Burkitt)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Spezielle_extranoduale_Lymphome\"><\/span><strong>Linfomas extranodais especializados:<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"#HSTL\"><strong>Linfoma hepatoespl\u00e9nico<\/strong> (HSTL)<\/a><\/li>\n\n\n\n<li><strong><a href=\"#IVGBL\">Linfoma intravascular de grandes c\u00e9lulas B<\/a><\/strong><\/li>\n\n\n\n<li><a href=\"#PEL\"><strong>Linfoma de efus\u00e3o prim\u00e1rio<\/strong> (PEL)<\/a><\/li>\n\n\n\n<li><strong><a href=\"#PEL\">Linfomas associados ao HHV8<\/a><\/strong><\/li>\n\n\n\n<li><strong><a href=\"#EMZL_MALT\">Linfoma MALT<\/a><\/strong> (est\u00f4mago, intestino, outros \u00f3rg\u00e3os)<\/li>\n\n\n\n<li><strong><a href=\"#EMZL_MALT\">Linfoma nodal\/extranodal da zona marginal<\/a><\/strong><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"T-Zell-_und_NK-Zell-Lymphome_20_aller_NHL\"><\/span><strong>Linfomas de c\u00e9lulas T e de c\u00e9lulas NK (20% de todos os LNH)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Periphere_T-Zell-Lymphome_PTCL\"><\/span><strong>Linfomas perif\u00e9ricos de c\u00e9lulas T (PTCL):<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong><a href=\"#PTCL-NOS\">Linfoma perif\u00e9rico de c\u00e9lulas T, NOS<\/a><\/strong> - forma mais comum de c\u00e9lulas T<\/li>\n\n\n\n<li><a href=\"#AITL\" data-type=\"internal\" data-id=\"#AITL\"><strong>Linfoma angioimunobl\u00e1stico de c\u00e9lulas T<\/strong> (AITL)<\/a><\/li>\n\n\n\n<li><a href=\"#PTFCL\"><strong>Linfoma folicular de c\u00e9lulas T auxiliares<\/strong> (PTFCL)<\/a><\/li>\n\n\n\n<li><a href=\"#HTZL\"><strong>Linfoma hepatoespl\u00e9nico de c\u00e9lulas T<\/strong> (tipo \u03b3\u03b4)<\/a><\/li>\n\n\n\n<li><strong><a href=\"#EATZL\">Linfoma de c\u00e9lulas T associado a enteropatia<\/a><\/strong><\/li>\n\n\n\n<li><a href=\"#ALCL\"><strong>Linfoma anapl\u00e1sico de grandes c\u00e9lulas<\/strong> (ALCL)<\/a><br>- ALK-positivo (melhor progn\u00f3stico)<br>- ALK-negativo<br>- Variante cut\u00e2nea prim\u00e1ria<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Kutane_T-Zell-Lymphome\"><\/span><strong>Linfomas cut\u00e2neos de c\u00e9lulas T:<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong><a href=\"#KTMF\">Micose fung\u00f3ide<\/a><\/strong> (forma cut\u00e2nea de c\u00e9lulas T mais comum)<\/li>\n\n\n\n<li><strong><a href=\"#SSMF\">S\u00edndrome de S\u00e9zary<\/a><\/strong> (envolvimento sangu\u00edneo da MF)<\/li>\n\n\n\n<li><strong><a href=\"#PKAGL\">Linfoma cut\u00e2neo prim\u00e1rio anapl\u00e1sico de grandes c\u00e9lulas<\/a><\/strong><\/li>\n\n\n\n<li><strong><a href=\"#KML\">Linfoma cut\u00e2neo da zona marginal<\/a><\/strong><\/li>\n\n\n\n<li><strong><a href=\"#KLKM\">Linfoma cut\u00e2neo com tatuagem granular do dedo m\u00e9dio<\/a><\/strong><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Lymphoblastische_Lymphome\"><\/span><strong>Linfomas linfobl\u00e1sticos:<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong><a href=\"#BALL\">Linfoma\/leucemia linfobl\u00e1stica B (B-ALL)<\/a><\/strong><br>mais frequentemente <\/li>\n\n\n\n<li><strong><a href=\"#TALL\">Linfoma\/leucemia linfobl\u00e1stica T (T-ALL)<\/a><\/strong><br>mais raros (e linfoma de c\u00e9lulas T)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Nota: Se &gt;25% blastos na BM (medula \u00f3ssea) ou no sangue, ent\u00e3o em vez <strong>Leucemia<\/strong>-Diagn\u00f3stico<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"NK-Zell-Lymphome\"><\/span><strong>Linfomas de c\u00e9lulas NK:<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong><a href=\"#ENKTL-NT\">Linfoma extranodal de c\u00e9lulas NK<\/a><\/strong> (associado ao EBV)<\/li>\n\n\n\n<li><a href=\"#ANKL\"><strong>Leucemia agressiva de c\u00e9lulas NK<\/strong> (ANKL)<\/a><\/li>\n\n\n\n<li><strong><a href=\"#CNKL\">Leucemia cr\u00f3nica de c\u00e9lulas NK<\/a><\/strong><\/li>\n<\/ul>\n\n\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Hodgkin-Lymphom_%E2%80%93_Verwandte_Erkrankungen\"><\/span><strong><strong>Linfoma de Hodgkin<\/strong> - Doen\u00e7as relacionadas<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"#NLDHL\">LH nodular com predomin\u00e2ncia de linf\u00f3citos<\/a><\/li>\n\n\n\n<li><a href=\"#PTLD\">Linfoma de grandes c\u00e9lulas B EBV-positivo (doen\u00e7a linfoproliferativa p\u00f3s-transplante)<\/a><\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Immunproliferative_Erkrankungen_Grenzfalle\"><\/span><strong>Doen\u00e7as imunoproliferativas e casos-limite<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong><a href=\"#IEG_MALT\">Linfomas MALT<\/a><\/strong> (Tecido linfoide associado \u00e0 mucosa)<\/li>\n\n\n\n<li><strong><a href=\"#IEG_LG\">Granulomatose linfomat\u00f3ide<\/a><\/strong><\/li>\n\n\n\n<li><strong><a href=\"#GANZ\">Granulomatose com vasculite preservadora de \u00f3rg\u00e3os (GANZL)<\/a><\/strong><\/li>\n\n\n\n<li><strong><a href=\"#IEG_EBVBL\">Linfoprolifera\u00e7\u00f5es de c\u00e9lulas B associadas ao EBV<\/a><\/strong><\/li>\n<\/ul>\n\n\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Epidemiologische_Ubersicht\"><\/span><strong>Panorama epidemiol\u00f3gico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><thead><tr><th>Tipo de linfoma<\/th><th>Frequ\u00eancia<\/th><th>Idade m\u00e9dia<\/th><th>5-Y. Sobreviv\u00eancia<\/th><\/tr><\/thead><tbody><tr><td><strong>Total de linfomas n\u00e3o-Hodgkin (LNH)<\/strong><\/td><td><strong>85-90%<\/strong><\/td><td><strong>65-70 J.<\/strong><\/td><td><strong>70%<\/strong><\/td><\/tr><tr><td><strong>Total Linfoma de Hodgkin (LH)<\/strong><\/td><td><strong>10-15%<\/strong><\/td><td><strong>40 J.<\/strong><\/td><td><strong>90%+<\/strong><\/td><\/tr><tr><td><\/td><td><\/td><td><\/td><td><\/td><\/tr><tr><td><strong>Subtipos de LNH mais importantes:<\/strong><\/td><td><\/td><td><\/td><td><\/td><\/tr><tr><td>Linfoma folicular (FL)<\/td><td>20% (da NHL)<\/td><td>65 J.<\/td><td>85-90%<\/td><\/tr><tr><td>DLBCL<\/td><td>35% (da NHL)<\/td><td>70 J.<\/td><td>65-75%<\/td><\/tr><tr><td>Leucemia linfoc\u00edtica pequena\/linfoma (CLL\/SLL)<\/td><td>15% (da NHL)<\/td><td>70 J.<\/td><td>75%+<\/td><\/tr><tr><td>Linfoma de Burkitt<\/td><td>2-3% (da NHL)<\/td><td>50 J.<\/td><td>80-90%<\/td><\/tr><tr><td>Linfoma angioimunobl\u00e1stico de c\u00e9lulas T (AITL)<\/td><td>2-3% (da NHL)<\/td><td>75 J.<\/td><td>32%<\/td><\/tr><tr><td>Linfoma MALT<\/td><td>5-10% (da NHL)<\/td><td>60 J.<\/td><td>80-90%<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klassifikation_nach_Biologie_Prognose\"><\/span><strong>Classifica\u00e7\u00e3o de acordo com a biologia (progn\u00f3stico)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Indolente<\/strong> (crescimento lento, menos hip\u00f3teses de recupera\u00e7\u00e3o, mas longos per\u00edodos de sobreviv\u00eancia)<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Linfoma folicular, CLL\/SLL, MALT<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Agressivo<\/strong> (crescimento r\u00e1pido, melhores hip\u00f3teses de recupera\u00e7\u00e3o com a quimioterapia moderna)<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>DLBCL, linfoma de Burkitt, linfoma de Hodgkin<\/li>\n<\/ul>\n\n\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differentielle_Darstellung_%E2%80%93_Non-Hodgkin-Lymphome\"><\/span>Representa\u00e7\u00e3o diferencial - <strong>Linfoma n\u00e3o-Hodgkin<\/strong>e<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"FL\"><span class=\"ez-toc-section\" id=\"Follikulares_Lymphom_FL\"><\/span><strong>Linfoma folicular (FL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">A classifica\u00e7\u00e3o atual da OMS (WHO-HAEM-5) divide os linfomas foliculares em:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Tipo cl\u00e1ssico (cFL)<\/strong><br>Corresponde aos graus anteriores 1, 2, 3A (indolente)<\/li>\n\n\n\n<li><strong>Linfoma folicular de grandes c\u00e9lulas B (FLBL)<\/strong><br>Corresponde ao antigo grau 3B (agressivo)<\/li>\n\n\n\n<li><strong>FL com carater\u00edsticas invulgares (uFL)<\/strong><br>nova entidade provis\u00f3ria<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Subtipos gen\u00e9ticos: 90% t\u00eam t(14;18)* com rearranjo BCL2; menos frequentemente t(8;14) com transloca\u00e7\u00e3o MYC (mau progn\u00f3stico); 70% regi\u00e3o de rutura maior (MBR)**, 10-15% regi\u00e3o de rutura menor (mbr)***.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">* t(14;18) - indica (de forma simplificada) uma transloca\u00e7\u00e3o entre o cromossoma 8 e o cromossoma 14. Escrito por extenso, seria t(8;14)(q24;q32), a transloca\u00e7\u00e3o complementada pelas posi\u00e7\u00f5es das bandas que s\u00e3o <strong>Localiza\u00e7\u00e3o citogen\u00e9tica exacta<\/strong> q, que quebra a banda&nbsp;<strong>q24<\/strong>&nbsp;do cromossoma 8 (gene MYC) e banda&nbsp;<strong>q32<\/strong>&nbsp;do cromossoma 14 (locus IGH).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">** O MBR est\u00e1 localizado no&nbsp;<strong>Gama de interruptores-\u03bc (S\u03bc)<\/strong>&nbsp;do locus IGH, imediatamente antes do gene da regi\u00e3o constante C\u03bc. Esta regi\u00e3o \u00e9 um alvo do gene&nbsp;<strong>recombina\u00e7\u00e3o espec\u00edfica de classe (recombina\u00e7\u00e3o de mudan\u00e7a de classe, CSR)<\/strong>&nbsp;nas c\u00e9lulas B, o que indica um processo fisiol\u00f3gico mal direcionado como causa da transloca\u00e7\u00e3o.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">*** A mbr tamb\u00e9m est\u00e1 na gama S\u03bc, mas um pouco&nbsp;<strong>a montante (5\u2032) at\u00e9 ao MBR<\/strong> e com <strong>aprox. 10-15 %<\/strong>&nbsp;est\u00e1 envolvida na transloca\u00e7\u00e3o t(8;14). Esta regi\u00e3o tamb\u00e9m \u00e9 atacada durante a CSR, mas com menos frequ\u00eancia do que a MBR.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Em ambos os casos (MBR e mbr), a transloca\u00e7\u00e3o resulta na&nbsp;<strong>Gene MYC (8q24)<\/strong>&nbsp;sob o controlo dos potenciadores fortes do&nbsp;<strong>IGH-Lokus<\/strong>&nbsp;que conduz a um&nbsp;<strong>sobreexpress\u00e3o constitutiva de MYC<\/strong>&nbsp;e, por conseguinte, conduz a uma prolifera\u00e7\u00e3o celular descontrolada.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Os restantes casos t\u00eam pontos de quebra noutras regi\u00f5es de comuta\u00e7\u00e3o (por exemplo, S\u03b1, S\u03b3) ou na regi\u00e3o JH, o que tamb\u00e9m significa que a&nbsp;<strong>Gene MYC (8q24)<\/strong>&nbsp;est\u00e1 sob o controlo de fortes elementos reguladores do locus IGH, que&nbsp;<strong>Sobreexpress\u00e3o constitutiva de MYC<\/strong>&nbsp;e, por conseguinte, provoca o desenvolvimento de tumores.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"LPL\"><span class=\"ez-toc-section\" id=\"Lymphoplasmozytisches_Lymphom_%E2%80%93_Waldenstrom-Makroglobulinamie\"><\/span><strong>Linfoma linfoplasmocit\u00e1rio - Macroglobulinemia de Waldenstr\u00f6m<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>Linfoma linfoplasmocit\u00e1rio (LPL)<\/strong>tamb\u00e9m&nbsp;<strong>Doen\u00e7a de Waldenstr\u00f6m-macroglobulinemia (WM)<\/strong>&nbsp;\u00e9 uma doen\u00e7a linfoproliferativa cr\u00f3nica rara que pertence ao grupo das neoplasias de c\u00e9lulas B maduras.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Caracteriza-se por uma&nbsp;<strong>Infiltra\u00e7\u00e3o linfoplasmocit\u00e1ria da medula \u00f3ssea<\/strong>, a produ\u00e7\u00e3o de um&nbsp;<strong>anticorpo monoclonal IgM (paraprote\u00edna)<\/strong>&nbsp;e uma forma maioritariamente indolente e de progress\u00e3o lenta.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A doen\u00e7a ocorre predominantemente em adultos mais velhos (idade m\u00e9dia de diagn\u00f3stico: 65-72 anos), sendo os homens afectados duas vezes mais do que as mulheres.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisch-morphologische_Merkmale\"><\/span><strong>Carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Histol\u00f3gico<\/strong>&nbsp;o linfoma apresenta um infiltrado denso, difuso ou folicular de pequenos linf\u00f3citos, linf\u00f3citos plasmocit\u00f3ides e plasm\u00f3citos na medula \u00f3ssea e noutros \u00f3rg\u00e3os<\/li>\n\n\n\n<li>As c\u00e9lulas tumorais s\u00e3o&nbsp;<strong>CD19+, CD20+, CD22+ (fraco)<\/strong>,&nbsp;<strong>CD5-, CD10-, CD23-, CD103-<\/strong>,&nbsp;<strong>CD27+<\/strong>,&nbsp;<strong>FMC7+<\/strong>,&nbsp;<strong>CD38+<\/strong>,&nbsp;<strong>CD52+<\/strong>&nbsp;e&nbsp;<strong>IgM+<\/strong><\/li>\n\n\n\n<li><strong>BCL2<\/strong>&nbsp;\u00e9 expresso em aproximadamente 98 casos de % e representa um alvo terap\u00eautico<\/li>\n\n\n\n<li>O&nbsp;<strong>Aumento do n\u00edvel de IgM<\/strong>&nbsp;provoca um aumento da viscosidade do sangue, o que pode resultar em sintomas como dores de cabe\u00e7a, tonturas, perturba\u00e7\u00f5es da vis\u00e3o e da audi\u00e7\u00e3o, hemorragias nasais e fen\u00f3meno de Raynaud<\/li>\n\n\n\n<li><strong>Sintomas carater\u00edsticos<\/strong>&nbsp;incluem: Sintomas B (febre, suores noturnos, perda de peso), anemia (palidez, fraqueza), trombocitopenia (tend\u00eancia para hemorragias), polineuropatia (formigueiro, dor nas extremidades) e crioglobulinemia\/doen\u00e7a da aglutinina fria com depend\u00eancia da agrega\u00e7\u00e3o de IgM do frio<\/li>\n\n\n\n<li><strong>Complica\u00e7\u00f5es<\/strong> pode ser amiloidose de cadeia leve (les\u00e3o de \u00f3rg\u00e3os), infiltra\u00e7\u00e3o de \u00f3rg\u00e3os (ba\u00e7o, aumento do f\u00edgado), infec\u00e7\u00f5es devido a imunossupress\u00e3o<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik\"><\/span><strong>Diagn\u00f3stico diferencial<\/strong>tique<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial inclui outras doen\u00e7as com produ\u00e7\u00e3o de IgM monoclonal ou infiltra\u00e7\u00e3o linfoplasmocit\u00e1ria:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Gamopatia monoclonal IgM de significado desconhecido (IgM-MGUS)<\/strong><br>IgM &lt; 30 g\/l, &lt; 10 plasm\u00f3citos % na medula \u00f3ssea, sem sintomas<br>Taxa de progress\u00e3o: 1,5-2 % por ano<\/li>\n\n\n\n<li><strong>Outros linfomas n\u00e3o Hodgkin<\/strong>:<br>- <strong>Linfoma da zona marginal (MZL)<\/strong><br>Pode ser secretora de IgM ou IgG, mas geralmente sem envolvimento da medula \u00f3ssea<br>- <strong>Leucemia linfoc\u00edtica cr\u00f3nica (B-CLL)<\/strong><br>CD5+, CD23+, CD20+, IgM-positivo, mas maioritariamente sem paraprote\u00edna IgM<br>- <strong>Linfoma difuso de grandes c\u00e9lulas B (DLBCL)<\/strong><br>Evolu\u00e7\u00e3o agressiva, imunofen\u00f3tipo diferente<\/li>\n\n\n\n<li><strong>Mieloma m\u00faltiplo (plasmocitoma)<\/strong><br>Les\u00f5es osteol\u00edticas, hipercalcemia, apenas raramente secre\u00e7\u00e3o de IgM<\/li>\n\n\n\n<li><strong>Hepatite, VIH, artrite reumatoide<\/strong><br>pode aumentar secundariamente a IgM<\/li>\n\n\n\n<li><strong>Outra IgM-LPL sem envolvimento da medula \u00f3ssea<\/strong>&nbsp;(LPL n\u00e3o-Morbus Waldenstr\u00f6m): por exemplo, LPL IgG\/IgA, LPL n\u00e3o-secretora (OMS 2022)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methoden\"><\/span><strong>M\u00e9todos de diagn\u00f3stico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico baseia-se numa combina\u00e7\u00e3o de testes cl\u00ednicos, laboratoriais e de gen\u00e9tica molecular:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Eletroforese do soro e da urina<\/strong>&nbsp;+&nbsp;<strong>Imunofixa\u00e7\u00e3o<\/strong><br>Dete\u00e7\u00e3o de uma prote\u00edna IgM monoclonal<\/li>\n\n\n\n<li><strong>Bi\u00f3psia da medula \u00f3ssea<\/strong><br>Confirma\u00e7\u00e3o de infiltra\u00e7\u00e3o linfoplasmocit\u00e1ria (&gt;10 c\u00e9lulas clonais %)<\/li>\n\n\n\n<li><strong>Citomorfologia<\/strong><br>Avalia\u00e7\u00e3o do esfrega\u00e7o de sangue e de medula \u00f3ssea<\/li>\n\n\n\n<li><strong>Imunofenotipagem (citometria de fluxo)<\/strong><br>CD19+, CD20+, CD22+, CD27+, CD38+, CD52+, IgM+, CD5-, CD23-<\/li>\n\n\n\n<li><strong>An\u00e1lise cromoss\u00f3mica<\/strong><br>Dele\u00e7\u00e3o do bra\u00e7o longo do cromossoma 6 (del(6q)) a ~50 %, ganho de 6p, ganhos dos cromossomas 4, 8, 3, 18, dele\u00e7\u00f5es no bra\u00e7o longo do cromossoma 13<\/li>\n\n\n\n<li><strong>FISH (hibrida\u00e7\u00e3o in situ por fluoresc\u00eancia)<\/strong>Dete\u00e7\u00e3o de del(6q), del(11q) (ATM), del(17p) (TP53) - este \u00faltimo com progress\u00e3o desfavor\u00e1vel<\/li>\n\n\n\n<li><strong>Gen\u00e9tica molecular (NGS)<\/strong><br>- <strong>Muta\u00e7\u00e3o MYD88 L265P<\/strong>Com&nbsp;<strong>~90-95 %<\/strong>&nbsp;dos doentes com MW -&nbsp;<strong>diagn\u00f3stico altamente espec\u00edfico<\/strong><br>- <strong>CXCR4-S338X (variante WHIM)<\/strong><br>Com&nbsp;<strong>~30 %<\/strong>&nbsp;- associada a uma resposta mais fraca ao ibrutinib, a uma evolu\u00e7\u00e3o mais agressiva<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie\"><\/span><strong>Terapia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">A terap\u00eautica depende dos sintomas, do risco, da idade, do estado geral e do gen\u00f3tipo:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>WM assintom\u00e1tica<\/strong> (Macroglobulinemia de Waldenstr\u00f6m)<br><strong>Observa\u00e7\u00e3o<\/strong>&nbsp;(\u201eobservar e esperar\u201c), esperan\u00e7a de vida compar\u00e1vel \u00e0 do grupo et\u00e1rio<\/li>\n\n\n\n<li><strong>Sintom\u00e1tico W<\/strong>M - <strong>Terapia de primeira linha<\/strong><br><strong>Quimioimunoterapia (CIT)<\/strong><br>- <strong>DRC (dexametasona-rituximab-ciclofosfamida)<\/strong>Para pacientes idosos ou fr\u00e1geis<br>- <strong>BR (Bendamustina-Rituximab)<\/strong>Para os doentes em forma, o controlo r\u00e1pido da doen\u00e7a<br><strong>Inibidores da BTK (BTKi)<\/strong><br>- <strong>Ibrutinib<\/strong>,&nbsp;<strong>Zanubrutinib<\/strong>:&nbsp;<strong>Indica\u00e7\u00e3o de primeira linha<\/strong>, especialmente em doentes com&nbsp;<strong>MYD88 L265P<\/strong><br><strong>N\u00e3o adequado para MYD88 WT \/ CXCR4 WT<\/strong><br>- Taxas de resposta elevadas (&gt;80 %), boa tolerabilidade, terapia cont\u00ednua<\/li>\n\n\n\n<li><strong>Terapias \u00e0 base de bortezomib<\/strong><br>(por exemplo, bortezomib-rituximab) - Controlo r\u00e1pido, para doentes com elevada carga de doen\u00e7a<\/li>\n\n\n\n<li><strong>Transplante de c\u00e9lulas estaminais<\/strong><br>Em doentes jovens e \u00e1geis com doen\u00e7a recorrente (raro)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose\"><\/span><strong>Previs\u00e3o<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Sobreviv\u00eancia global mediana<\/strong><br>&gt;10 anos (em doentes assintom\u00e1ticos, mesmo pr\u00f3ximo da popula\u00e7\u00e3o normal)<\/li>\n\n\n\n<li><strong>Factores de progn\u00f3stico<\/strong><br><strong>Favor\u00e1vel<\/strong>Muta\u00e7\u00e3o MYD88 L265P, CXCR<\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"CLL_SLL\"><span class=\"ez-toc-section\" id=\"Kleines_lymphozytische_Leukamie_Lymphom_CLLSLL\"><\/span><strong>Leucemia linfoc\u00edtica pequena \/ linfoma (CLL\/SLL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Este \u00e9 um <strong>entidade homog\u00e9nea<\/strong> (n\u00e3o um subtipo no sentido cl\u00e1ssico), mas com subcategorias de progn\u00f3stico:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>IGHV mutado<\/strong> (~50%)<br>Melhor progn\u00f3stico<\/li>\n\n\n\n<li><strong>IGHV n\u00e3o mutado<\/strong> (~50%)<br>Pior progn\u00f3stico<\/li>\n\n\n\n<li><strong>Del(13q)<\/strong><br>Fator de risco favor\u00e1vel<\/li>\n\n\n\n<li><strong>Del(11q)<\/strong> \/ <strong>Muta\u00e7\u00e3o TP53<\/strong><br>factores de risco desfavor\u00e1veis<\/li>\n\n\n\n<li><strong>Del(17p)<\/strong> \/ <strong>Muta\u00e7\u00e3o TP53<\/strong><br>Progn\u00f3stico muito desfavor\u00e1vel<\/li>\n\n\n\n<li><strong>Cari\u00f3tipo complexo<\/strong> (\u22653 aberra\u00e7\u00f5es)<br>pior<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>Leucemia linfoc\u00edtica cr\u00f3nica (LLC)<\/strong>&nbsp;e isso&nbsp;<strong>linfoma de pequenas c\u00e9lulas B (LBE)<\/strong>&nbsp;s\u00e3o considerados uma entidade comum de linfomas indolentes de c\u00e9lulas B de acordo com a classifica\u00e7\u00e3o da OMS de 2022.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Ambas as doen\u00e7as t\u00eam um perfil imunofenot\u00edpico e histol\u00f3gico id\u00eantico, mas diferem clinicamente no local de envolvimento: Na&nbsp;<strong>CLL<\/strong>&nbsp;domina o&nbsp;<strong>infiltra\u00e7\u00e3o leuc\u00e9mica do sangue perif\u00e9rico e da medula \u00f3ssea<\/strong>, enquanto o&nbsp;<strong>SLL<\/strong>&nbsp;o&nbsp;<strong>Envolvimento extramedular dos g\u00e2nglios linf\u00e1ticos, ba\u00e7o ou outros \u00f3rg\u00e3os<\/strong>&nbsp;est\u00e1 em primeiro plano (linf\u00f3citos no sangue &lt; 5 \u00d7 10\u2079\/L).<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_Merkmale\"><\/span><strong>Carater\u00edsticas cl\u00ednicas<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Frequ\u00eancia<\/strong><br>A LLC \u00e9 a doen\u00e7a leuc\u00e9mica mais comum na Alemanha, com uma taxa de novos casos de cerca de 5 600 por ano<\/li>\n\n\n\n<li><strong>Idade m\u00e9dia de in\u00edcio<\/strong><br>72 anos (homens), 76 anos (mulheres)<\/li>\n\n\n\n<li><strong>Sintomas<\/strong><br>Muitos doentes s\u00e3o assintom\u00e1ticos na altura do diagn\u00f3stico. Com a doen\u00e7a avan\u00e7ada&nbsp;<strong>Sintomas B<\/strong>&nbsp;(febre, suores noturnos, perda de peso),&nbsp;<strong>Linfadenopatia<\/strong>,&nbsp;<strong>Hepato- e esplenomegalia<\/strong>,&nbsp;<strong>Citopenias<\/strong>&nbsp;(anemia, trombocitopenia) ou&nbsp;<strong>Citopenias auto-imunes<\/strong>&nbsp;sobre<\/li>\n\n\n\n<li><strong>Esfrega\u00e7o de sangue<\/strong><br>Predomin\u00e2ncia de linf\u00f3citos pequenos e maduros com&nbsp;<strong>Cromatina densa e turva<\/strong>,&nbsp;<strong>rebordo citoplasm\u00e1tico estreito<\/strong>&nbsp;e&nbsp;<strong>A sombra do n\u00facleo de Gumprecht<\/strong>&nbsp;(t\u00edpico, mas n\u00e3o patognom\u00f3nico)<\/li>\n\n\n\n<li><strong>Medula \u00f3ssea<\/strong><br>Infiltra\u00e7\u00e3o por pequenos linf\u00f3citos, frequentemente com perda dos centros germinativos<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-2\"><\/span>Diagn\u00f3stico diferencial<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Kriterien_nach_IWCLL\"><\/span><strong>Crit\u00e9rios de diagn\u00f3stico (de acordo com IWCLL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Linfocitose permanente (&gt; 3 meses) com \u2265 5 \u00d7 10\u2079\/L c\u00e9lulas B monoclonais no sangue perif\u00e9rico<\/li>\n\n\n\n<li>Morfol\u00f3gico: predomin\u00e2ncia de linf\u00f3citos pequenos e maduros no esfrega\u00e7o de sangue<\/li>\n\n\n\n<li>Imunofen\u00f3tipo:&nbsp;<strong>CD5+, CD19+, CD23+<\/strong>,&nbsp;<strong>CD20(dim), CD79b(dim)<\/strong>,&nbsp;<strong>CD200+, ROR1+<\/strong>;&nbsp;<strong>fraco\/sIg<\/strong>,&nbsp;<strong>sem CD10<\/strong>,&nbsp;<strong>nenhum FMC7<\/strong><\/li>\n\n\n\n<li><strong>Monoclonalidade<\/strong>Dete\u00e7\u00e3o da restri\u00e7\u00e3o da cadeia leve (kappa ou lambda) utilizando CD19\/Ig\u03ba ou CD19\/Ig\u03b3<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnosen\"><\/span><strong>Diagn\u00f3sticos diferenciais<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><tbody><tr><td class=\"has-text-align-left\" data-align=\"left\">Doen\u00e7a<\/td><td class=\"has-text-align-left\" data-align=\"left\">Crit\u00e9rios de demarca\u00e7\u00e3o<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Linfocitose monoclonal de c\u00e9lulas B (MBL)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">&lt; 5 \u00d7 10\u2079\/L c\u00e9lulas B monoclonais,&nbsp;<strong>Sem sintomas<\/strong>,&nbsp;<strong>Sem aumento dos g\u00e2nglios linf\u00e1ticos<\/strong>,&nbsp;<strong>Sem citopenias<\/strong><\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Linfoma de c\u00e9lulas do manto (LCM)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>t(11;14)(q13;q32)<\/strong>,&nbsp;<strong>CD5+<\/strong>, mas&nbsp;<strong>CD23-<\/strong>,&nbsp;<strong>ciclina D1+<\/strong>,&nbsp;<strong>Prolinf\u00f3citos CD5+ &gt; 15%<\/strong>&nbsp;(para progress\u00e3o prolinfoc\u00edtica)<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Leucemia prolinfoc\u00edtica de c\u00e9lulas B (B-PLL)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>&gt; 55% Prolinf\u00f3citos<\/strong>&nbsp;no sangue,&nbsp;<strong>CD5-<\/strong>,&nbsp;<strong>CD23-<\/strong>,&nbsp;<strong>CD20+<\/strong>,&nbsp;<strong>CD200-<\/strong><\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Leucemia de c\u00e9lulas pilosas (HCL)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>\u201eC\u00e9lulas ciliadas\u201c<\/strong>&nbsp;com uma estrutura citoplasm\u00e1tica irregular,&nbsp;<strong>CD103+, CD123+, CD25+<\/strong>,&nbsp;<strong>TRAP+<\/strong>,&nbsp;<strong>fibrose reticular na medula \u00f3ssea<\/strong><\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Transforma\u00e7\u00e3o de Richter (CLL \u2192 DLBCL)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Progress\u00e3o do linfoma extramedular<\/strong>&nbsp;(2-5% dos casos),&nbsp;<strong>Curso agressivo<\/strong>,&nbsp;<strong>Tipo DLBCL<\/strong>&nbsp;(centrobl\u00e1stico\/imunobl\u00e1stico),&nbsp;<strong>CD30+, CD10+, BCL6+<\/strong>,&nbsp;<strong>BCL2-<\/strong><\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methoden-2\"><\/span><strong>M\u00e9todos de diagn\u00f3stico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Citomorfologia<\/strong><br>Sangue EDTA, obrigat\u00f3rio<\/li>\n\n\n\n<li><strong>Imunofenotipagem<\/strong><br>EDTA ou heparina<br><strong>Pontua\u00e7\u00e3o de Matutes<\/strong>&nbsp;Classifica\u00e7\u00e3o<\/li>\n\n\n\n<li><strong>PEIXE<\/strong><br>Painel standard<br><strong>del(13q), del(11q), +12, del(17p)<\/strong>,&nbsp;<strong>Rearranjos do IGH<\/strong>&nbsp;(por exemplo, t(11;14), t(14;18))<\/li>\n\n\n\n<li><strong>An\u00e1lise cromoss\u00f3mica<\/strong><br><strong>Heparina<\/strong>-sangue;&nbsp;<strong>Cari\u00f3tipo complexo (\u22653 aberra\u00e7\u00f5es)<\/strong>&nbsp;tem um progn\u00f3stico desfavor\u00e1vel<\/li>\n\n\n\n<li><strong>Gen\u00e9tica molecular<\/strong><br><strong>Estado da muta\u00e7\u00e3o do IGHV<\/strong>&nbsp;(n\u00e3o mutado = desfavor\u00e1vel),&nbsp;<strong>TP53, ATM, NOTCH1, SF3B1<\/strong>-muta\u00e7\u00f5es<\/li>\n\n\n\n<li><strong>Dete\u00e7\u00e3o de MRD<\/strong><br>Sensibilidade \u2265 10-\u2074; importante para a monitoriza\u00e7\u00e3o da terap\u00eautica<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-2\"><\/span><strong>Previs\u00e3o<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O progn\u00f3stico \u00e9 altamente heterog\u00e9neo e \u00e9 determinado por v\u00e1rios factores:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Estado da muta\u00e7\u00e3o do IGHV<\/strong>:&nbsp;<strong>N\u00e3o mutado (U-CLL)<\/strong>&nbsp;= desfavor\u00e1vel<\/li>\n\n\n\n<li><strong>Hipermutados (H-CLL)<\/strong>&nbsp;= favor\u00e1vel<\/li>\n\n\n\n<li><strong>Aberra\u00e7\u00f5es cromoss\u00f3micas (FISH)<\/strong>:<br>- <strong>del(17p)<\/strong>:&nbsp;<strong>Desfavor\u00e1vel<\/strong>,&nbsp;<strong>Altera\u00e7\u00e3o do TP53<\/strong>&nbsp;\u2192 Resist\u00eancia \u00e0 terapia.<br>- <strong>del(11q)<\/strong>Desfavor\u00e1vel, frequentemente com linfadenopatia.<\/li>\n\n\n\n<li><strong>Cari\u00f3tipo complexo<\/strong><br>Fator de progn\u00f3stico independente (desfavor\u00e1vel).&nbsp;<\/li>\n\n\n\n<li><strong>Gen\u00e9tica molecular<\/strong><br><strong>NOTCH1, SF3B1, BIRC3<\/strong>-muta\u00e7\u00f5es \u2192 desfavor\u00e1veis, especialmente em caso de recorr\u00eancia<\/li>\n\n\n\n<li><strong>CLL-IPI (\u00cdndice Internacional de Progn\u00f3stico)<\/strong><br>Tem em conta a idade, o est\u00e1dio de Binet, a \u03b2\u2082 microglobulina, o IGHV, o del(17p), a muta\u00e7\u00e3o TP53<br>Valioso para&nbsp;<strong>PFS<\/strong> (sobreviv\u00eancia livre de progress\u00e3o), menos para&nbsp;<strong>OS<\/strong> (sobreviv\u00eancia global) sob terap\u00eautica dirigida<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-2\"><\/span><strong>Terapia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">A terapia depende do&nbsp;<strong>Necessidade de tratamento<\/strong>,&nbsp;<strong>Factores de progn\u00f3stico<\/strong>&nbsp;e&nbsp;<strong>Perfil do doente<\/strong>.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Indikation_zur_Therapie_nach_iwCLLOnkopedia\"><\/span><strong>Indica\u00e7\u00e3o para a terap\u00eautica (de acordo com a iwCLL\/Onkopedia)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Sintomas<\/strong>Sintomas B, citopenias, progress\u00e3o da linfadenopatia<\/li>\n\n\n\n<li><strong>Crit\u00e9rios laboratoriais<\/strong>:&nbsp;<strong>Linf\u00f3citos &gt; 30 \u00d7 10\u2079\/L<\/strong>,&nbsp;<strong>Tempo de duplica\u00e7\u00e3o celular &lt; 12 meses<\/strong>,&nbsp;<strong>citopenias progressivas<\/strong><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Behandlungsoptionen\"><\/span><strong>Op\u00e7\u00f5es de tratamento<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Terapias direcionadas (terapia prim\u00e1ria)<\/strong><br>- <strong>Ibrutinib (inibidor da BTK)<\/strong><br><strong>Padr\u00e3o para altera\u00e7\u00f5es TP53 ou IGHV n\u00e3o mutado<\/strong><br>- <strong>Venetoclax (inibidor da BCL-2)<\/strong><br>Combina\u00e7\u00e3o com&nbsp;<strong>Obinutuzumab<\/strong><br>especialmente com&nbsp;<strong>del(17p)<\/strong>&nbsp;ou&nbsp;<strong>Muta\u00e7\u00e3o TP53<\/strong><\/li>\n\n\n\n<li><strong>Terapia combinada (para pacientes mais aptos)<\/strong><br>- <strong>Obinutuzumab + clorambucil<\/strong>&nbsp;ou&nbsp;<strong>FCR (fludarabina, ciclofosfamida, rituximab)<\/strong><br>apenas para&nbsp;<strong>risco favor\u00e1vel (hipermutado, sem altera\u00e7\u00e3o do TP53)<\/strong><\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Marginalzonen-Lymphome\"><\/span><strong>Linfomas da zona marginal<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Linfoma da zona marginal (MZL)<\/strong>&nbsp;s\u00e3o um grupo de linfomas indolentes de c\u00e9lulas B que podem ser divididos em tr\u00eas subtipos principais de acordo com a sua localiza\u00e7\u00e3o prim\u00e1ria:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>MZL extranodal (linfoma MALT)<\/strong><\/li>\n\n\n\n<li><strong>MZL nodal (nMZL)<\/strong><\/li>\n\n\n\n<li><strong>MZL espl\u00e9nico (SMZL)<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Os tr\u00eas subtipos t\u00eam origem no tecido de c\u00e9lulas B maduras, mas apresentam carater\u00edsticas cl\u00ednicas, gen\u00e9ticas e terap\u00eauticas diferentes.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Extranodales_Marginalzonen-Lymphom_MALT-Lymphom\"><\/span><strong>Linfoma extranodal da zona marginal (linfoma MALT)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Origem<\/strong><br>Principalmente em \u00f3rg\u00e3os n\u00e3o linf\u00e1ticos (por exemplo, est\u00f4mago, gl\u00e2ndulas salivares, olhos, pele, pulm\u00f5es)<\/li>\n\n\n\n<li><strong>Frequ\u00eancia<\/strong><br>Aproximadamente 8% de todos os linfomas, sendo o est\u00f4mago a localiza\u00e7\u00e3o mais frequente (30-35%)<\/li>\n\n\n\n<li><strong>Patog\u00e9nese<\/strong><br>Frequentemente associada \u00e0 estimula\u00e7\u00e3o cr\u00f3nica de antig\u00e9nios por&nbsp;<strong>Helicobacter pylori<\/strong>-Infe\u00e7\u00e3o (est\u00f4mago) <br>ou doen\u00e7as auto-imunes (por exemplo, s\u00edndrome de Sj\u00f6gren, tiroidite de Hashimoto)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-3\"><\/span><strong>Diagn\u00f3stico diferencial<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Para ser distinguido de&nbsp;<strong>linfoma difuso de grandes c\u00e9lulas B (DLBCL)<\/strong>,&nbsp;<strong>linfoma folicular<\/strong>&nbsp;e&nbsp;<strong>leucemia linfoc\u00edtica cr\u00f3nica (LLC)<\/strong><\/li>\n\n\n\n<li>Cl\u00e1ssico&nbsp;<strong>les\u00f5es linfoepiteliais<\/strong>&nbsp;com invas\u00e3o do epit\u00e9lio por c\u00e9lulas B clonais s\u00e3o carater\u00edsticas<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnosemethodik\"><\/span><strong>Metodologia de diagn\u00f3stico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Exame histol\u00f3gico do \u00f3rg\u00e3o afetado (por exemplo, biopsia do est\u00f4mago)<\/li>\n\n\n\n<li><strong>Gastroscopia<\/strong>,&nbsp;<strong>Colonoscopia<\/strong>,&nbsp;<strong>Ultrassom<\/strong>,&nbsp;<strong>PET-CT<\/strong>&nbsp;(para encena\u00e7\u00e3o)<\/li>\n\n\n\n<li>Imunohistoqu\u00edmica:&nbsp;<strong>CD20+, CD79a+, CD10-, CD5-, CD23-<\/strong><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie_und_Prognose\"><\/span>Terapia e progn\u00f3stico<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Primeira linha<\/strong>:&nbsp;<strong>Erradica\u00e7\u00e3o antibi\u00f3tica da H. pylori<\/strong>&nbsp;(taxas de remiss\u00e3o at\u00e9 80%)<\/li>\n\n\n\n<li>Em caso de n\u00e3o resposta ou de linfoma MALT extrag\u00e1strico:&nbsp;<strong>Radioterapia<\/strong>&nbsp;(24 Gy) ou&nbsp;<strong>Terapia de sistema<\/strong>&nbsp;(por exemplo.&nbsp;&nbsp;<strong>Rituximab + bendamustina<\/strong>,&nbsp;<strong>Rituximab + clorambucil<\/strong>)<\/li>\n\n\n\n<li><strong>Zanubrutinib<\/strong>&nbsp;(inibidor da BTK) como uma nova abordagem para a recorr\u00eancia ou doen\u00e7a refract\u00e1ria<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Nodales_Marginalzonen-Lymphom_nMZL\"><\/span><strong>Linfoma da zona marginal nodal (nMZL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O <strong>Linfoma da zona marginal nodal<\/strong> \u00e9 um linfoma de c\u00e9lulas B raro e indolente, que representa cerca de 0,5-1% de todos os linfomas e 10% de todos os MZL.&nbsp;<strong>G\u00e2nglios linf\u00e1ticos<\/strong>, sem infesta\u00e7\u00e3o extranodal ou espl\u00e9nica.<br>Pertence ao grupo dos linfomas da zona marginal (MZL), que tamb\u00e9m inclui o linfoma extranodal (linfoma MALT) e o linfoma da zona marginal espl\u00e9nica.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_Merkmale-2\"><\/span>Carater\u00edsticas cl\u00ednicas<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Semelhante ao&nbsp;<strong>linfoma folicular<\/strong><br>Estadio avan\u00e7ado aquando do diagn\u00f3stico, aumento dos g\u00e2nglios linf\u00e1ticos, envolvimento da medula \u00f3ssea (aprox. 30%)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzierung_vom_splenischen_und_extranodalen_MZL\"><\/span>Diferencia\u00e7\u00e3o entre MZL espl\u00e9nico e extranodal<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>nMZL<\/strong><br>A infesta\u00e7\u00e3o prim\u00e1ria afecta&nbsp;<strong>apenas os g\u00e2nglios linf\u00e1ticos<\/strong><br>Est\u00e1&nbsp;<strong>Sem infesta\u00e7\u00e3o do ba\u00e7o (espl\u00e9nico)<\/strong>&nbsp;e&nbsp;<strong>Sem infesta\u00e7\u00e3o extranodal<\/strong>&nbsp;(por exemplo, est\u00f4mago, gl\u00e2ndula salivar, olho) antes de<\/li>\n\n\n\n<li><strong>MZL espl\u00e9nico<\/strong><br>Infesta\u00e7\u00e3o do&nbsp;<strong>Ba\u00e7o<\/strong>, frequentemente com&nbsp;<strong>Infiltra\u00e7\u00e3o da medula \u00f3ssea<\/strong>&nbsp;e&nbsp;<strong>envolvimento leuc\u00e9mico<\/strong>&nbsp;do sangue perif\u00e9rico<\/li>\n\n\n\n<li><strong>MZL extranodal (linfoma MALT)<\/strong><br>Come\u00e7a em&nbsp;<strong>\u00f3rg\u00e3os n\u00e3o linf\u00e1ticos<\/strong>&nbsp;(por exemplo, est\u00f4mago, gl\u00e2ndula salivar, olho) e mostra frequentemente uma associa\u00e7\u00e3o com inflama\u00e7\u00e3o cr\u00f3nica (por exemplo.&nbsp;<em>Helicobacter pylori<\/em>, S\u00edndroma de Sj\u00f6gren)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzierung_von_anderen_indolenten_B-Zell-Lymphomen\"><\/span>Diferencia\u00e7\u00e3o de outros linfomas indolentes de c\u00e9lulas B<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Linfoma folicular (FL)<\/strong><br>Quadro cl\u00ednico e abordagem terap\u00eautica semelhantes, mas estrutura celular histologicamente diferente (arquitetura folicular na FL, estrutura semelhante \u00e0 zona marginal na nMZL)<\/li>\n\n\n\n<li><strong>Linfoma linfoplasmocit\u00e1rio<\/strong><br>Podem apresentar carater\u00edsticas cl\u00ednicas e histol\u00f3gicas sobrepostas; diferencia\u00e7\u00e3o por imunofen\u00f3tipos espec\u00edficos (por exemplo, aus\u00eancia de CD5, CD10, CD23 em nMZL, mas express\u00e3o de marcadores de c\u00e9lulas plasm\u00e1ticas em LPL)<\/li>\n\n\n\n<li><strong>Linfomas de c\u00e9lulas B maduras<\/strong><br>Diferencia\u00e7\u00e3o por imunohistoqu\u00edmica (por exemplo.&nbsp;<strong>CD20+, CD5-, CD10-, CD23-<\/strong>, t\u00edpico para nMZL)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnosemethodik-2\"><\/span>Metodologia de diagn\u00f3stico<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Diagn\u00f3stico histol\u00f3gico por&nbsp;<strong>Bi\u00f3psia de g\u00e2nglios linf\u00e1ticos<\/strong>&nbsp;(diagn\u00f3stico de exclus\u00e3o)<\/li>\n\n\n\n<li>Estadiamento de acordo com&nbsp;<strong>Classifica\u00e7\u00e3o de Ann Arbor<\/strong><\/li>\n\n\n\n<li><strong>PET-CT<\/strong>,&nbsp;<strong>Bi\u00f3psia da medula \u00f3ssea<\/strong>,&nbsp;<strong>Contagem sangu\u00ednea<\/strong>,&nbsp;<strong>Testes de fun\u00e7\u00e3o pulmonar<\/strong>,&nbsp;<strong>ECG\/eco card\u00edaco<\/strong>&nbsp;(antes da terapia)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-3\"><\/span>Terapia<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Primeira linha<\/strong><br><strong>Rituximab + quimioterapia<\/strong>&nbsp;(por exemplo.&nbsp;&nbsp;<strong>Bendamustina<\/strong>, CVP, CHOP)<\/li>\n\n\n\n<li><strong>Terapia de manuten\u00e7\u00e3o com rituximab<\/strong>&nbsp;(2 anos) mostra uma sobreviv\u00eancia prolongada livre de progress\u00e3o<\/li>\n\n\n\n<li>Em caso de recidiva:&nbsp;<br><strong>rituximab\/quimioterapia renovada<\/strong>,&nbsp;<strong>Terapia de alta dose com transplante aut\u00f3logo de c\u00e9lulas estaminais<\/strong>&nbsp;(para reca\u00eddas precoces)<\/li>\n\n\n\n<li>Para doen\u00e7a refract\u00e1ria<br><strong>Inibidores da BTK (ibrutinib, zanubrutinib)<\/strong>&nbsp;ou&nbsp;<strong>Inibidores da PI3K (idelalisib, copanlisib)<\/strong><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Splenisches_Marginalzonen-Lymphom_SMZL\"><\/span><strong>Linfoma da zona marginal espl\u00e9nica (SMZL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O <strong>Linfoma da zona marginal espl\u00e9nica (SMZL)<\/strong>&nbsp;\u00e9 um com aprox.&nbsp;<strong>1-2%<\/strong>&nbsp;de todos os linfomas; e aprox.&nbsp;&nbsp;<strong>2%<\/strong>&nbsp;todos os MZL, neoplasia rara e indolente das c\u00e9lulas B que se manifesta principalmente no ba\u00e7o e \u00e9 frequentemente acompanhada por envolvimento da medula \u00f3ssea e do sangue perif\u00e9rico.&nbsp;<br>O diagn\u00f3stico diferencial \u00e9 dif\u00edcil devido \u00e0 falta de marcadores celulares espec\u00edficos e requer um diagn\u00f3stico multimodal.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_Merkmale-3\"><\/span>Carater\u00edsticas cl\u00ednicas<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li>S\u00e3o t\u00edpicos&nbsp;<strong>Esplenomegalia<\/strong>,&nbsp;<strong>Infiltra\u00e7\u00e3o da medula \u00f3ssea<\/strong>&nbsp;e vari\u00e1vel&nbsp;<strong>envolvimento leuc\u00e9mico<\/strong>&nbsp;do sangue perif\u00e9rico<br>A linfadenopatia generalizada \u00e9 rara<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Zytomorphologie\"><\/span>Citomorfologia<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>O sangue perif\u00e9rico cont\u00e9m&nbsp;<strong>c\u00e9lulas linf\u00f3ides com vilosidades curtas e polares<\/strong>,&nbsp;<strong>linf\u00f3citos plasmocitoides<\/strong>&nbsp;e linf\u00f3citos inconsp\u00edcuos.  As c\u00e9lulas apresentam uma morfologia vilosa e madura<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Histologie\"><\/span>Histologia<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>O ba\u00e7o apresenta uma infesta\u00e7\u00e3o das polpas branca e vermelha, sendo que a polpa branca est\u00e1 tipicamente aumentada. A medula \u00f3ssea apresenta&nbsp;<strong>infiltrados micronodulares<\/strong>&nbsp;de linf\u00f3citos at\u00edpicos<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Immunphanotyp\"><\/span>Imunofen\u00f3tipo<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">As c\u00e9lulas tumorais expressam&nbsp;<strong>Antig\u00e9nios de c\u00e9lulas Pan B<\/strong>&nbsp;(CD19, CD20, CD22, CD79a),&nbsp;<strong>sIgM\/IgD<\/strong>&nbsp;e&nbsp;<strong>FMC7<\/strong>, mas s\u00e3o&nbsp;<strong>negativo para CD5, CD10, CD23, CD43, CD103, ciclina D1 e anexina A1<\/strong>.&nbsp;<br>O&nbsp;<strong>Misexpress\u00e3o de CD5<\/strong>&nbsp;\u00e9 crucial para a diferencia\u00e7\u00e3o entre a leucemia linfoc\u00edtica cr\u00f3nica (LLC) e o linfoma das c\u00e9lulas do manto (LCM)<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Zytogenetik_und_molekulare_Marker\"><\/span>Citogen\u00e9tica e marcadores moleculares<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Dele\u00e7\u00e3o 7q<\/strong>Em aprox.&nbsp;<strong>30-40% dos casos<\/strong>&nbsp;detet\u00e1vel - uma carater\u00edstica mas n\u00e3o um tra\u00e7o espec\u00edfico<\/li>\n\n\n\n<li><strong>Trissomia 3q<\/strong>&nbsp;e&nbsp;<strong>Ganhos de 1q, 8q, 12q, 18<\/strong>&nbsp;s\u00e3o frequentemente<\/li>\n\n\n\n<li><strong>Altera\u00e7\u00f5es gen\u00e9ticas moleculares<\/strong>Muta\u00e7\u00f5es em&nbsp;<strong>NOTCH2 (10-25%)<\/strong>,&nbsp;<strong>KLF2 (10-40%)<\/strong>,&nbsp;<strong>TP53<\/strong>&nbsp;e&nbsp;<strong>MYD88<\/strong>&nbsp;s\u00e3o frequentes e est\u00e3o associados a uma evolu\u00e7\u00e3o menos favor\u00e1vel.<\/li>\n\n\n\n<li><strong>Sem transloca\u00e7\u00e3o carater\u00edstica<\/strong>&nbsp;como no linfoma folicular (t(14;18)) ou no linfoma de c\u00e9lulas do manto (t(11;14))<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-4\"><\/span>Diagn\u00f3stico diferencial<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Linfoma\/leucemia de c\u00e9lulas B espl\u00e9nicas com nucl\u00e9olos proeminentes (SBLPN)<\/strong>Muta\u00e7\u00f5es no MAP2K1, morfologia celular espec\u00edfica<\/li>\n\n\n\n<li><strong>Leucemia linfoc\u00edtica cr\u00f3nica (LLC)<\/strong>CD5-positivo, CD23-positivo, morfologia celular diferente<\/li>\n\n\n\n<li><strong>Linfoma de c\u00e9lulas do manto (LCM)<\/strong>CD5-positivo, ciclina D1-positivo, t(11;14) presente<\/li>\n\n\n\n<li><strong>Leucemia de c\u00e9lulas pilosas (HZL)<\/strong>Muta\u00e7\u00e3o BRAF V600E, \u201ec\u00e9lulas ciliadas\u201c no sangue, CD11c-positivo<\/li>\n\n\n\n<li><strong>Linfoma linfoplasmocit\u00e1rio (LPL)<\/strong>Muta\u00e7\u00e3o MYD88 L265P, muta\u00e7\u00e3o CXCR4, macroglobulinemia IgM<\/li>\n\n\n\n<li><strong>Linfoma espl\u00e9nico difuso de pequenas c\u00e9lulas B da polpa vermelha (SDRPL)<\/strong>Histologicamente diferente, envolvimento mais frequente da polpa vermelha<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnosemethodik-3\"><\/span><strong>Metodologia de diagn\u00f3stico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Tipagem de linf\u00f3citos perif\u00e9ricos<\/strong>,&nbsp;<strong>Bi\u00f3psia da medula \u00f3ssea<\/strong>,&nbsp;<strong>Prepara\u00e7\u00e3o para a esplenectomia<\/strong>&nbsp;(raro)<\/li>\n\n\n\n<li><strong>Imunofen\u00f3tipo<\/strong>:&nbsp;<strong>CD20+, CD79a+, sIgM\/IgD+, CD5-, CD10-, CD23-, CD43-, Annexin A1-, Cyclin D1-<\/strong>.<\/li>\n\n\n\n<li><strong>Ki67 para colorir<\/strong>:&nbsp;<strong>Padr\u00e3o Targetoid<\/strong>&nbsp;(carater\u00edstica)<\/li>\n\n\n\n<li><strong>Gen\u00e9tica molecular<\/strong>:&nbsp;<strong>NOTCH2-<\/strong>&nbsp;(10-25%) e&nbsp;<strong>KLF2-<\/strong>&nbsp;(10-40%) muta\u00e7\u00f5es \u2192 evolu\u00e7\u00e3o menos favor\u00e1vel<\/li>\n\n\n\n<li><strong>Histologia do ba\u00e7o<\/strong><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie_und_Prognose-2\"><\/span><strong>Terapia<\/strong> e previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Indica\u00e7\u00e3o para a terapia<\/strong><br>Apenas em casos de citopenia (Hb &lt;10 g\/dl, plaquetas &lt;80.000, neutr\u00f3filos &lt;1000) ou esplenomegalia sintom\u00e1tica<\/li>\n\n\n\n<li><strong>Op\u00e7\u00f5es terap\u00eauticas<\/strong><br>- <strong>Esplenectomia<\/strong>&nbsp;(op\u00e7\u00e3o equivalente).<br>- <strong>Rituximab em monoterapia<\/strong><br>- ou&nbsp;<strong>Rituximab + bendamustina<\/strong>.<\/li>\n\n\n\n<li>Sobreviv\u00eancia global mediana &gt;10 anos<br><strong>POD24<\/strong>&nbsp;(progress\u00e3o no prazo de 24 meses) \u2192 sobreviv\u00eancia mediana 3-5 anos<\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"CL\"><span class=\"ez-toc-section\" id=\"Primar_kutane_Lymphome_CL\"><\/span>Linfomas cut\u00e2neos prim\u00e1rios (LC)<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Os linfomas cut\u00e2neos prim\u00e1rios (LC) s\u00e3o um grupo heterog\u00e9neo de doen\u00e7as linfoproliferativas da pele caracterizadas por um envolvimento cut\u00e2neo isolado sem envolvimento sist\u00e9mico. S\u00e3o respons\u00e1veis por cerca de&nbsp;<strong>70 %<\/strong>&nbsp;de linfomas cut\u00e2neos (linfomas de c\u00e9lulas T) e&nbsp;<strong>25 %<\/strong>&nbsp;(linfomas de c\u00e9lulas B), sendo que os restantes 5 % incluem formas raras.  A doen\u00e7a ocorre predominantemente na meia-idade e na idade avan\u00e7ada, com uma incid\u00eancia anual de cerca de&nbsp;<strong>1.000 novos casos na Alemanha<\/strong>.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisch-morphologische_Merkmale-2\"><\/span><strong>Carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Forma mais comum<\/strong>:&nbsp;<strong>Micose fung\u00f3ide (MF)<\/strong><br>come\u00e7a normalmente com placas eritematosas que evoluem para les\u00f5es escamosas e espessadas (placas \u201epapel de cigarro\u201c)<br>Mais tarde, podem ocorrer n\u00f3dulos tumorais e envolvimento generalizado<\/li>\n\n\n\n<li><strong>Linfoma cut\u00e2neo prim\u00e1rio de c\u00e9lulas B (CBCL)<\/strong><br>- <strong>Linfoma folicular<\/strong>Placas solit\u00e1rias ou poucas, lisas, vermelhas a castanho-avermelhadas no tronco, na face ou na cabe\u00e7a. Clinicamente, \u00e9 frequente&nbsp;<strong>assintom\u00e1tico<\/strong><br>- <strong>Linfoma da zona marginal<\/strong>P\u00e1pulas ou placas m\u00faltiplas, frequentemente na perna<br>- <strong>S\u00edndrome de S\u00e9zary<\/strong>Eritrodermia generalizada, linfadenopatia, prurido, pseudopapilomas,&nbsp;<strong>CD4+\/CD56+<\/strong>-c\u00e9lulas do sangue<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnose\"><\/span><strong>Diagn\u00f3stico diferencial<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cl\u00ednica<\/strong><br>Psor\u00edase, eczema at\u00f3pico, dermatite de contacto cr\u00f3nica, l\u00edquen plano, l\u00fapus eritematoso, tuberculose cut\u00e2nea, micose fung\u00f3ide vs. pitir\u00edase rubra pilar<\/li>\n\n\n\n<li><strong>Histol\u00f3gico<\/strong><br>Pseudolinfomas (por exemplo.&nbsp;<em>Linfadenose cut\u00e2nea benigna<\/em>), infiltrado linfocit\u00e1rio benigno, linfadenopatia reactiva, cutis laxa, pele frouxa granulomatosa, linfoma subcut\u00e2neo tipo paniculite<\/li>\n\n\n\n<li><strong>Diagn\u00f3sticos diferenciais espec\u00edficos para CBCL<\/strong><br><strong>Linfoma folicular cut\u00e2neo prim\u00e1rio<\/strong>&nbsp;vs. centros germinais reactivos,&nbsp;<strong>Linfoma da zona marginal<\/strong>&nbsp;vs. inflama\u00e7\u00e3o cr\u00f3nica,&nbsp;<strong>linfoma difuso de grandes c\u00e9lulas<\/strong>&nbsp;vs. melanoma maligno, linfoma de Hodgkin, carcinoma<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methoden-3\"><\/span><strong>M\u00e9todos de diagn\u00f3stico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Exame cl\u00ednico<\/strong><br>Hist\u00f3ria cl\u00ednica pormenorizada, exame da pele e dos g\u00e2nglios linf\u00e1ticos<\/li>\n\n\n\n<li><strong>Histologia<\/strong><br>Bi\u00f3psia com&nbsp;<strong>v\u00e1rios n\u00edveis<\/strong>, preferido para les\u00f5es n\u00e3o erodidas<\/li>\n\n\n\n<li><strong>Imunohistoqu\u00edmica<\/strong><br>CD20, CD79a (c\u00e9lulas B), CD3, CD4, CD5, CD7 (c\u00e9lulas T), CD30 (para doen\u00e7as CD30+), Bcl-2, Bcl-6, CD10<\/li>\n\n\n\n<li><strong>Biologia molecular<\/strong><br>- <strong>PCR para genes de imunoglobulinas clonais<\/strong>&nbsp;(IGK, IGH) - Dete\u00e7\u00e3o de uma popula\u00e7\u00e3o clonal de c\u00e9lulas tumorais<br>- <strong>FISH ou citogen\u00e9tica<\/strong><br>t(14;18)(q32;q21) no linfoma folicular (apenas em cerca de 30-50 % dos casos cut\u00e2neos prim\u00e1rios)<\/li>\n\n\n\n<li><strong>Encena\u00e7\u00e3o<\/strong> - <strong>Classifica\u00e7\u00e3o TNM<\/strong>&nbsp;(ISCL\/EORTC):<br>- <strong>T<\/strong> - Tamanho e extens\u00e3o das les\u00f5es cut\u00e2neas (T1-T4)<br>- <strong>N<\/strong> - Envolvimento dos g\u00e2nglios linf\u00e1ticos (N0-N3)<br>- <strong>M<\/strong> - Infesta\u00e7\u00e3o sist\u00e9mica (M0-M1)<\/li>\n\n\n\n<li><strong>Imagiologia<\/strong><br><strong>PET\/CT<\/strong>&nbsp;para a dete\u00e7\u00e3o de infesta\u00e7\u00e3o subcl\u00ednica (recomendado para est\u00e1dios superiores)<\/li>\n\n\n\n<li><strong>Bi\u00f3psia da medula \u00f3ssea<\/strong><br>Se houver suspeita de dissemina\u00e7\u00e3o sist\u00e9mica (por exemplo, linfoma difuso de grandes c\u00e9lulas)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-4\"><\/span><strong>Terapia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Les\u00f5es localizadas (est\u00e1dio I\/II)<\/strong><br>- <strong>Radioterapia<\/strong>Controlo local permanente do tumor para&nbsp;<strong>90-100 %<\/strong>&nbsp;o CTCL e&nbsp;<strong>95-100 %<\/strong>&nbsp;de casos de CBCL<br>- <strong>Terapia t\u00f3pica<\/strong>: <strong>Mostarda de azoto (mecloretamina)<\/strong>,&nbsp;<strong>Bexaroteno gel<\/strong>&nbsp;(para MF),&nbsp;<strong>Imiquimod<\/strong>,&nbsp;<strong>Corticoster\u00f3ides<\/strong><\/li>\n\n\n\n<li><strong>Les\u00f5es que se multiplicam ou localmente avan\u00e7adas<\/strong><br>- <strong>Fototerapia<\/strong>UVB, PUVA (para MF)<\/li>\n\n\n\n<li><strong>Terapia sist\u00e9mica<\/strong><br>- <strong>Rituximab<\/strong>&nbsp;(anticorpo anti-CD20): Padr\u00e3o para linfomas de c\u00e9lulas B (R-CHOP, R-CVP)<br>- <strong>Regime CHOP<\/strong>&nbsp;(ciclofosfamida, doxorrubicina, vincristina, prednisona) ou&nbsp;<strong>R-CHOP<\/strong>&nbsp;para formas agressivas<br>- <strong>Brentuximab vedotina<\/strong>&nbsp;(CD30+)<\/li>\n\n\n\n<li><strong>Profilaxia da s\u00edndrome de S\u00e9zary<\/strong>Terapia sist\u00e9mica, por exemplo.&nbsp;<strong>Metotrexato<\/strong>,&nbsp;<strong>Bexaroteno<\/strong>,&nbsp;<strong>Alemtuzumab<\/strong>.&nbsp;<\/li>\n\n\n\n<li><strong>Terapia baseada em estudos<\/strong>No caso de les\u00f5es precoces (\u201ebaixo peso\u201c), um&nbsp;<strong>\u201eEstrat\u00e9gia \u201cesperar para ver<\/strong>&nbsp;com&nbsp;<strong>Rituximab<\/strong>&nbsp;(estudo RESORT) como sendo superior \u00e0 observa\u00e7\u00e3o<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-3\"><\/span><strong>Previs\u00e3o<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Bom progn\u00f3stico (&gt;5 anos de sobreviv\u00eancia)<\/strong><br>- Micose fung\u00f3ide (fases iniciais), principalmente cut\u00e2nea&nbsp;<strong>linfoma folicular de c\u00e9lulas B<\/strong>,&nbsp;<strong>Linfoma da zona marginal<\/strong>,&nbsp;<strong>Papulose linfomat\u00f3ide<\/strong>,&nbsp;<strong>Reticulose pagetoide<\/strong>.<br>- <strong>Taxa de sobreviv\u00eancia a 5 anos<\/strong>:&nbsp;<strong>at\u00e9 95 %<\/strong>&nbsp;para linfoma folicular sem envolvimento da medula \u00f3ssea<\/li>\n\n\n\n<li><strong>Previs\u00e3o a m\u00e9dio prazo (2-5 anos)<\/strong><br>S\u00edndrome de S\u00e9zary, MF foliculotr\u00f3pica, linfoma difuso de grandes c\u00e9lulas B (outros tipos)<\/li>\n\n\n\n<li><strong>Mau progn\u00f3stico (&lt;2 anos)<\/strong><br>Linfoma intravascular de grandes c\u00e9lulas B,&nbsp;<strong>linfoma de c\u00e9lulas T gama\/delta<\/strong>,&nbsp;<strong>CD4+\/CD56+<\/strong>-neoplasia,&nbsp;<strong>Linfoma de c\u00e9lulas NK\/T<\/strong><\/li>\n\n\n\n<li><strong>Factores de progn\u00f3stico<\/strong><br>Localiza\u00e7\u00e3o na perna (pior progn\u00f3stico), infiltra\u00e7\u00e3o da medula \u00f3ssea,&nbsp;<strong>Express\u00e3o de Bcl-2<\/strong>,&nbsp;<strong>t(14;18)-negatividade<\/strong>,&nbsp;<strong>LDH elevada<\/strong>,&nbsp;<strong>Positividade para CD56<\/strong><\/li>\n<\/ul>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\"><strong>Perceber<\/strong>O progn\u00f3stico melhorou gra\u00e7as \u00e0s terapias modernas (p. ex.&nbsp;<strong>Rituximab<\/strong>,&nbsp;<strong>Imunoterapias<\/strong>), mas faltam estat\u00edsticas actualizadas e de grande escala que reflictam plenamente esta evolu\u00e7\u00e3o.  O&nbsp;<strong>An\u00e1lise de clonalidade<\/strong>&nbsp;\u00e9 um importante fator de progn\u00f3stico que ainda n\u00e3o foi tido em conta em estudos mais antigos.<\/p>\n<\/blockquote>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"PDBZLM\"><span class=\"ez-toc-section\" id=\"Primar_duodenales_B-Zell-Lymphom_MALT-Typ\"><\/span>Linfoma duodenal prim\u00e1rio de c\u00e9lulas B (tipo MALT)<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Um linfoma duodenal prim\u00e1rio de c\u00e9lulas B do tecido linfoide associado \u00e0 mucosa (linfoma MALT) \u00e9 uma forma rara de linfoma maligno n\u00e3o-Hodgkin que se desenvolve no duodeno. Desenvolve-se a partir de c\u00e9lulas B e cresce \u00e0 custa do tecido linfoide da mucosa.<br>Embora seja raro, \u00e9 um dos linfomas extranodais mais comuns, sendo o est\u00f4mago o local mais comum, seguido do duodeno e de outras regi\u00f5es gastrointestinais.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Em geral, os linfomas MALT s\u00e3o&nbsp;<strong>raro<\/strong>&nbsp;e fazer cerca de&nbsp;<strong>7-8 %<\/strong>&nbsp;de todos os linfomas n\u00e3o-Hodgkin recentemente diagnosticados.  O&nbsp;<strong>O est\u00f4mago \u00e9 a localiza\u00e7\u00e3o mais comum<\/strong>&nbsp;(30-60 % de linfomas MALT), enquanto a&nbsp;<strong>Duodeno significativamente menos frequentemente afetado<\/strong>&nbsp;\u00e9.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">De acordo com as diretrizes e estudos actuais, os linfomas MALT encontram-se na&nbsp;<strong>todo o trato gastrointestinal<\/strong>&nbsp;apenas aproximadamente&nbsp;<strong>5 % de casos<\/strong>, A maioria est\u00e1 localizada no est\u00f4mago.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">N\u00e3o est\u00e3o dispon\u00edveis dados espec\u00edficos sobre a incid\u00eancia no duodeno, mas considera-se que \u00e9&nbsp;<strong>Localiza\u00e7\u00e3o mais rara no intestino delgado<\/strong>&nbsp;s\u00e3o considerados. De acordo com as estimativas&nbsp;<strong>apenas cerca de 3 % de todos os linfomas MALT afectam o trato intestinal<\/strong>, e a por\u00e7\u00e3o duodenal \u00e9 m\u00ednima.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>Incid\u00eancia de todos os linfomas MALT<\/strong>&nbsp;\u00e9 sobre&nbsp;<strong>1 caso por cada 313.000 pessoas por ano<\/strong>, com uma idade m\u00e9dia de in\u00edcio de&nbsp;<strong>65 anos<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Uma luz&nbsp;<strong>dom\u00ednio feminino<\/strong>&nbsp;\u00e9 descrita, em contraste com os linfomas g\u00e1stricos, que tendem a afetar os homens.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Um linfoma MALT duodenal prim\u00e1rio \u00e9 um&nbsp;<strong>Doen\u00e7a indolente, maioritariamente localizada<\/strong>, que se caracterizam por&nbsp;<strong><em>H. pylori<\/em>-erradica\u00e7\u00e3o<\/strong>&nbsp;pode ser tratada. O&nbsp;<strong>O diagn\u00f3stico requer confirma\u00e7\u00e3o histol\u00f3gica e imunohistoqu\u00edmica<\/strong>, complementado por&nbsp;<strong>M\u00e9todos de biologia molecular e de imagiologia<\/strong>.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_Merkmale-4\"><\/span>Carater\u00edsticas cl\u00ednicas<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Sintomas<\/strong><br>Muitas vezes inespec\u00edficos, como&nbsp;<strong>Fadiga, perda de peso, dor abdominal, n\u00e1useas ou hemorragias<\/strong>&nbsp;do trato gastrointestinal superior<br>Em alguns casos, pode levar a&nbsp;<strong>sintomas obstrutivos<\/strong>&nbsp;pode ocorrer se o linfoma se infiltrar na parede intestinal ou causar uma estenose<\/li>\n\n\n\n<li><strong>Imagem cl\u00ednica<\/strong>A doen\u00e7a geralmente progride&nbsp;<strong>indolente<\/strong>, mas a progress\u00e3o pode levar a uma&nbsp;<strong>Transforma\u00e7\u00e3o em linfoma difuso de grandes c\u00e9lulas B (DLBCL)<\/strong>&nbsp;ocorrer. Esta \u00e9 considerada uma evolu\u00e7\u00e3o clinicamente desfavor\u00e1vel<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-5\"><\/span>Diagn\u00f3stico diferencial<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Os diagn\u00f3sticos diferenciais incluem:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Doen\u00e7as inflamat\u00f3rias benignas<\/strong>&nbsp;do duodeno (por exemplo, enterite cr\u00f3nica, doen\u00e7a de Crohn)<\/li>\n\n\n\n<li><strong>Tumores malignos<\/strong>&nbsp;do duodeno (por exemplo, adenocarcinoma, GIST)<\/li>\n\n\n\n<li><strong>Outros linfomas n\u00e3o Hodgkin<\/strong>&nbsp;(por exemplo, DLBCL, linfoma folicular)<\/li>\n\n\n\n<li><strong>Infec\u00e7\u00f5es<\/strong>&nbsp;(por exemplo.&nbsp;<em>Helicobacter pylori<\/em>-gastrite associada, tamb\u00e9m relevante para os linfomas MALT do duodeno)<\/li>\n\n\n\n<li><strong>Doen\u00e7as auto-imunes<\/strong>&nbsp;(por exemplo, doen\u00e7a cel\u00edaca, enterite autoimune)&nbsp;<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methoden-4\"><\/span>M\u00e9todos de diagn\u00f3stico<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Endoscopia com biopsia<\/strong><br>O&nbsp;<strong>Histologia<\/strong>&nbsp;apresenta um&nbsp;<strong>Popula\u00e7\u00e3o de linf\u00f3citos infiltrantes<\/strong>&nbsp;na mucosa e submucosa, frequentemente com&nbsp;<strong>Estrutura semelhante a uma zona de bainha<\/strong><\/li>\n\n\n\n<li><strong>Imunohistoqu\u00edmica<\/strong><br>Confirma a g\u00e9nese das c\u00e9lulas B:&nbsp;<strong>CD20+, CD79a+, PAX5+<\/strong>,&nbsp;<strong>CD10-<\/strong>,&nbsp;<strong>BCL2+<\/strong>,&nbsp;<strong>MUM1-<\/strong>.&nbsp;&nbsp;<strong>CD5-<\/strong>&nbsp;e&nbsp;<strong>CD23-<\/strong>&nbsp;ajuda a diferenciar de CLL\/SLL<\/li>\n\n\n\n<li><strong>An\u00e1lise de clonalidade<\/strong><br>Prova de um&nbsp;<strong>Clonalidade das c\u00e9lulas B<\/strong>&nbsp;(por exemplo, por PCR para rearranjos do gene IgH)<\/li>\n\n\n\n<li><strong>An\u00e1lises biol\u00f3gicas moleculares<\/strong><br>- <strong>PEIXE<\/strong><br>Exclus\u00e3o de transloca\u00e7\u00f5es como&nbsp;<strong>t(11;18)(q21;q21)<\/strong>&nbsp;(BIRC3-MALT1), que est\u00e3o associados \u00e0 resist\u00eancia \u00e0 terapia<br>- <strong>Perfil de express\u00e3o dos genes<\/strong>: <br>Subclassifica\u00e7\u00e3o de acordo com&nbsp;<strong>COO (C\u00e9lula de Origem)<\/strong>&nbsp;- Tipo GCB ou tipo ABC - tem relev\u00e2ncia progn\u00f3stica<\/li>\n\n\n\n<li><strong>Imagiologia<\/strong><br>- <strong>TAC ou RMN do abd\u00f3men<\/strong>&nbsp;para a fase de prepara\u00e7\u00e3o<br>- <strong>FDG-PET\/CT<\/strong>&nbsp;\u00e9 recomendado em casos de suspeita de est\u00e1dio avan\u00e7ado ou de transforma\u00e7\u00e3o, uma vez que os linfomas MALT s\u00e3o frequentemente&nbsp;<strong>baixa avidez de FDG<\/strong>&nbsp;exposi\u00e7\u00e3o<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-5\"><\/span>Terapia<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Primeira escolha para o envolvimento duodenal isolado e evid\u00eancia de&nbsp;<em>H. pylori<\/em><\/strong>:&nbsp;<strong>Terapia antibi\u00f3tica para erradica\u00e7\u00e3o<\/strong>, que em at\u00e9&nbsp;<strong>50-70% dos casos<\/strong>&nbsp;conduz a uma remiss\u00e3o completa&nbsp;<\/li>\n\n\n\n<li><strong>Com negativo&nbsp;<em>H. pylori<\/em>-estado ou resist\u00eancia \u00e0 terap\u00eautica<\/strong><br>- <strong>Radioterapia<\/strong> Muito eficaz para les\u00f5es localizadas (por exemplo, no duodeno), com elevadas taxas de remiss\u00e3o<br><strong>- Quimioterapia<\/strong> em estado avan\u00e7ado ou transforma\u00e7\u00e3o em DLBCL:&nbsp;<strong>R-CHOP<\/strong>&nbsp;(rituximab, ciclofosfamida, doxorrubicina, vincristina, prednisona).<br>- <strong>Novas terapias<\/strong> para cursos recidivantes ou refract\u00e1rios:&nbsp;<br>\u2013 \u2013 <strong>Inibidores da BTK (por exemplo, ibrutinib)<\/strong><br>\u2013 \u2013 <strong>Inibidores de BCL2 (por exemplo, venetoclax)<\/strong>, especialmente com&nbsp;<em>H. pylori<\/em>-negativo ou&nbsp;<em>t(11;18)<\/em>-casos positivos.&nbsp;<\/li>\n\n\n\n<li><strong>Cirurgia<\/strong> apenas indicado para complica\u00e7\u00f5es como hemorragia ou perfura\u00e7\u00e3o, e n\u00e3o como terapia curativa.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-4\"><\/span>Previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>O progn\u00f3stico \u00e9 bom com diagn\u00f3stico e tratamento precoces<\/strong>, mas torna-se desfavor\u00e1vel em caso de transforma\u00e7\u00e3o ou de marcadores gen\u00e9ticos espec\u00edficos.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Favor\u00e1vel para isolados,&nbsp;<em>H. pylori<\/em>-les\u00e3o positiva<\/strong> - Taxa de sobreviv\u00eancia a 10 anos &gt;&nbsp;<strong>75%<\/strong>.<\/li>\n\n\n\n<li><strong>Menos favor\u00e1vel \u00e0 transforma\u00e7\u00e3o em DLBCL<\/strong> - deteriora-se significativamente; requer uma terapia agressiva.&nbsp;<\/li>\n\n\n\n<li><strong>Factores de progn\u00f3stico desfavor\u00e1vel<\/strong>:\n<ul class=\"wp-block-list\">\n<li><strong>t(11;18)(q21;q21)<\/strong>-transloca\u00e7\u00e3o<\/li>\n\n\n\n<li><strong>Express\u00e3o de CD5<\/strong><\/li>\n\n\n\n<li><strong>Localiza\u00e7\u00e3o fora do est\u00f4mago<\/strong>&nbsp;(por exemplo, duodeno)<\/li>\n\n\n\n<li><strong>Fase III\/IV<\/strong><\/li>\n\n\n\n<li><strong>LDH elevada<\/strong><\/li>\n\n\n\n<li><strong>N\u00famero de \u00f3rg\u00e3os extranodais<\/strong>&nbsp;(de acordo com o IPI)&nbsp;<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisch-morphologische_Merkmale-3\"><\/span>Carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Morfologia<\/strong><br>Infiltra\u00e7\u00e3o da mucosa e da submucosa por&nbsp;<strong>Linf\u00f3citos de tamanho pequeno a m\u00e9dio<\/strong>&nbsp;com&nbsp;<strong>forma centr\u00edpeta do n\u00facleo da c\u00e9lula<\/strong>,&nbsp;<strong>Boa diferencia\u00e7\u00e3o<\/strong>,&nbsp;<strong>Baixa taxa de prolifera\u00e7\u00e3o (Ki-67 &lt; 10%)<\/strong><\/li>\n\n\n\n<li><strong>Imunofen\u00f3tipo<\/strong><br><strong>CD20+, CD79a+, CD10-, BCL2+, MUM1-, CD5-, CD23-<\/strong><\/li>\n\n\n\n<li><strong>Gen\u00e9tica<\/strong><br><strong>t(11;18)(q21;q21)<\/strong>&nbsp;em 20-40% dos casos,&nbsp;<strong>t(1;14)(p22;q32)<\/strong>&nbsp;raro,&nbsp;<strong>Transloca\u00e7\u00f5es BCL10<\/strong>&nbsp;poss\u00edvel<\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"DLBCL\"><span class=\"ez-toc-section\" id=\"Diffus_Groszelliges_B-Zell-Lymphom_DLBCL\"><\/span><strong>Linfoma difuso de grandes c\u00e9lulas B (DLBCL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">O <strong>Linfoma difuso de grandes c\u00e9lulas B (DLBCL)<\/strong>&nbsp;\u00e9 a forma mais comum de linfoma n\u00e3o-Hodgkin em adultos e caracteriza-se por uma evolu\u00e7\u00e3o cl\u00ednica agressiva.&nbsp;<br>Desenvolve-se a partir de c\u00e9lulas B maduras e \u00e9 classificada na atual classifica\u00e7\u00e3o da OMS (WHO-HAEM5) e na Classifica\u00e7\u00e3o Internacional de Consenso (ICC) como&nbsp;<strong>DLBCL, NOS (n\u00e3o classificado noutra parte)<\/strong>&nbsp;\u00e9 definido, pelo que se recomenda uma subdivis\u00e3o em subtipos moleculares.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Molekulare_Subtypen_Cell_of_Origin_COO\"><\/span><strong>Subtipos moleculares (c\u00e9lula de origem, COO)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>GCB-DLBCL (c\u00e9lulas B do tipo centro germinal)<\/strong><br>Semelhante ao desenvolvimento de c\u00e9lulas B no centro germinal<br>Tem um melhor progn\u00f3stico com uma sobreviv\u00eancia livre de progress\u00e3o a 5 anos de&nbsp;<strong>70-80%<\/strong><\/li>\n\n\n\n<li><strong>ABC-DLBCL (c\u00e9lulas B activadas)<\/strong><br>Semelhante \u00e0s c\u00e9lulas B activadas fora do centro germinal<br>Caracterizada por um progn\u00f3stico menos favor\u00e1vel, com uma sobreviv\u00eancia sem progress\u00e3o de 5 anos de&nbsp;<strong>40-50%<\/strong><\/li>\n\n\n\n<li><strong>10-15% dos casos<\/strong>&nbsp;n\u00e3o pode atualmente ser atribu\u00eddo a um subinfotipo<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_Merkmale-5\"><\/span><strong>Carater\u00edsticas cl\u00ednicas<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Principais locais de manifesta\u00e7\u00e3o<\/strong><br>G\u00e2nglios linf\u00e1ticos, ba\u00e7o, medula \u00f3ssea, \u00f3rg\u00e3os extranodais (por exemplo, trato gastrointestinal, pele)<\/li>\n\n\n\n<li><strong>Sintomas B<\/strong>&nbsp;(febre, suores noturnos, perda de peso) s\u00e3o comuns<\/li>\n\n\n\n<li><strong>Factores de progn\u00f3stico<\/strong><br>Idade &gt;60 anos, est\u00e1dio avan\u00e7ado (III-IV), LDH elevada, pontua\u00e7\u00e3o IPI elevada, massa tumoral grande (volume &gt;7,5 cm), infiltra\u00e7\u00e3o da medula \u00f3ssea, sexo masculino, defici\u00eancia de vitamina D<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostische_Abgrenzung\"><\/span><strong>Diagn\u00f3stico diferencial<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O DLBCL, NOS deve ser diferenciado de outros linfomas de grandes c\u00e9lulas B, incluindo:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Linfomas altamente malignos de c\u00e9lulas B (HGBL) com rearranjos MYC e BCL2 e\/ou BCL6<\/strong><br>(linfomas \u201edouble-hit\u201c ou \u201etriple-hit\u201c), que s\u00e3o considerados entidades independentes<\/li>\n\n\n\n<li><strong>Linfoma de grandes c\u00e9lulas B com rearranjo IRF4<\/strong>&nbsp;(entidade definitiva)<\/li>\n\n\n\n<li><strong>DLBCL prim\u00e1rio do sistema nervoso central<\/strong>,&nbsp;<strong>do test\u00edculo<\/strong>&nbsp;ou&nbsp;<strong>a Vitroretina<\/strong><\/li>\n\n\n\n<li><strong>DLBCL EBV-positivo<\/strong>,&nbsp;<strong>DLBCL positivo para KSHV\/HHV8<\/strong>,&nbsp;<strong>DLBCL associado \u00e0 fibrina<\/strong>&nbsp;e&nbsp;<strong>HGBL com aberra\u00e7\u00e3o 11q<\/strong><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Kriterien\"><\/span><strong>Crit\u00e9rios de diagn\u00f3stico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Os diagn\u00f3sticos padr\u00e3o incluem<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Exame histopatol\u00f3gico<\/strong>&nbsp;de uma biopsia de g\u00e2nglio linf\u00e1tico<\/li>\n\n\n\n<li><strong>Imunohistoqu\u00edmica<\/strong>&nbsp;com painel de marcadores (CD20, CD10, BCL6, MUM1, CD5, CD30, MYC, BCL2)<\/li>\n\n\n\n<li><strong>An\u00e1lise da express\u00e3o gen\u00e9tica<\/strong>&nbsp;para determinar o subtipo de COO (padr\u00e3o de ouro, mas n\u00e3o um servi\u00e7o padr\u00e3o fornecido pelas companhias de seguros de sa\u00fade)<\/li>\n\n\n\n<li><strong>Citogen\u00e9tica e an\u00e1lises de gen\u00e9tica molecular<\/strong>&nbsp;(transloca\u00e7\u00f5es MYC, BCL2, BCL6, muta\u00e7\u00f5es em EZH2, MYD88, CARD11, CREBBP)<\/li>\n\n\n\n<li><strong>Imagiologia<\/strong>&nbsp;(TAC, PET-CT) e&nbsp;<strong>Exame da medula \u00f3ssea<\/strong>&nbsp;para a fase de prepara\u00e7\u00e3o<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie_und_Prognose-3\"><\/span><strong>Terapia<\/strong> e previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Terapia de primeira linha<\/strong><br><strong>Esquema R-CHOP<\/strong>&nbsp;(rituximab, ciclofosfamida, doxorrubicina, vincristina, prednisona) para doentes com risco baixo a interm\u00e9dio<\/li>\n\n\n\n<li><strong>Alternativas<\/strong><br><strong>Pola-R-CHP<\/strong>&nbsp;(com polatuzumab vedotina) para risco interm\u00e9dio a elevado<\/li>\n\n\n\n<li><strong>Recorrente\/refrat\u00e1rio<\/strong><br><strong>Terapia com c\u00e9lulas CAR-T<\/strong>&nbsp;(por exemplo, tisagenlecleucel, axicabtagen-ciloleucel),&nbsp;<strong>Anticorpos biespec\u00edficos<\/strong>&nbsp;(epcoritamab, glofitamab, odronextamab),&nbsp;<strong>Loncastuximab tesirina<\/strong>&nbsp;ou&nbsp;<strong>Transplante aut\u00f3logo de c\u00e9lulas estaminais<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Se n\u00e3o for tratado, o DLBCL torna-se rapidamente letal, mas com as terapias modernas, at\u00e9&nbsp;<strong>70% de cura do doente<\/strong>.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"pMBCL\"><span class=\"ez-toc-section\" id=\"Primar_mediastinales_B-Zell-Lymphom_pMBCL\"><\/span><strong>Linfoma prim\u00e1rio de c\u00e9lulas B do mediastino (pMBCL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Linfoma prim\u00e1rio de c\u00e9lulas B do mediastino (PMBCL)<\/strong>&nbsp;\u00e9 um subtipo raro e agressivo de linfoma n\u00e3o-Hodgkin (LNH), que pode causar cerca de.&nbsp;&nbsp;<strong>2-4 representa % de todos os LNH<\/strong>&nbsp;e sobretudo&nbsp;<strong>mulheres jovens com idades compreendidas entre os 30 e os 40 anos, em m\u00e9dia<\/strong>&nbsp;(idade m\u00e9dia de in\u00edcio de cerca de 35 anos).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Originalmente classificado como um subtipo de linfoma difuso de grandes c\u00e9lulas B (DLBCL), foi inclu\u00eddo como uma entidade independente na classifica\u00e7\u00e3o da OMS desde 2001, uma vez que se distingue por carater\u00edsticas cl\u00ednicas, patol\u00f3gicas e moleculares espec\u00edficas.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_Prasentation\"><\/span>Apresenta\u00e7\u00e3o cl\u00ednica<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O PMBCL \u00e9 criado no&nbsp;<strong>mediastino anterior<\/strong>&nbsp;(entre os pulm\u00f5es, atr\u00e1s do esterno) e conduz a sintomas t\u00edpicos como o crescimento invasivo local:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Acumula\u00e7\u00e3o de influ\u00eancia superior<\/strong>&nbsp;(por exemplo, uma veia vis\u00edvel na parede tor\u00e1cica),<\/li>\n\n\n\n<li><strong>Compress\u00e3o das vias a\u00e9reas<\/strong>&nbsp;ou obstru\u00e7\u00e3o,<\/li>\n\n\n\n<li><strong>Constri\u00e7\u00e3o do es\u00f3fago<\/strong>,<\/li>\n\n\n\n<li><strong>Tamponamento peric\u00e1rdico<\/strong>,<\/li>\n\n\n\n<li><strong>Trombose das veias cervicais<\/strong>,<\/li>\n\n\n\n<li><strong>Derrames pleurais<\/strong>,<\/li>\n\n\n\n<li><strong>S\u00edndrome de lise tumoral<\/strong>&nbsp;(raro).<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">A qu\u00edmica laboratorial apresenta frequentemente uma&nbsp;<strong>Aumento da desidrogenase l\u00e1ctica (LDH)<\/strong>&nbsp;e&nbsp;<strong>Sintomas B<\/strong>&nbsp;(febre, suores noturnos, perda de peso) em cerca de metade dos doentes.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Pathogenese_und_Diagnostik\"><\/span>Patog\u00e9nese e diagn\u00f3stico<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O PMBCL difere significativamente de outros subtipos de DLBCL a n\u00edvel molecular:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Ativa\u00e7\u00e3o constitutiva da via de sinaliza\u00e7\u00e3o NF-\u03baB e JAK\/STAT<\/strong><\/li>\n\n\n\n<li><strong>Amplifica\u00e7\u00e3o frequente do locus 9p24.1<\/strong>&nbsp;com sobreexpress\u00e3o de&nbsp;<strong>PD-L1 e PD-L2<\/strong>&nbsp;- uma raz\u00e3o central para a efic\u00e1cia do&nbsp;<strong>Inibidores PD-1<\/strong>&nbsp;como&nbsp;<strong>Pembrolizumab<\/strong>&nbsp;e&nbsp;<strong>Nivolumab<\/strong><\/li>\n\n\n\n<li><strong>Positividade CD30<\/strong>&nbsp;(semelhante ao linfoma de Hodgkin cl\u00e1ssico)<\/li>\n\n\n\n<li><strong>Sem imunoglobulinas<\/strong>&nbsp;(em contraste com outros linfomas de c\u00e9lulas B)<\/li>\n\n\n\n<li><strong>Semelhan\u00e7a com as c\u00e9lulas de Reed-Sternberg<\/strong>&nbsp;do linfoma de Hodgkin cl\u00e1ssico (LHc), o que torna o diagn\u00f3stico mais dif\u00edcil<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico \u00e9 baseado numa&nbsp;<strong>Bi\u00f3psia de g\u00e2nglios linf\u00e1ticos<\/strong>&nbsp;com an\u00e1lises histol\u00f3gicas, imunohistoqu\u00edmicas e de biologia molecular.<br><strong>ADN tumoral circulante (ctDNA)<\/strong>&nbsp;est\u00e1 a ser investigado como um novo biomarcador para diagn\u00f3stico e acompanhamento.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie_und_Prognose-4\"><\/span>Terapia e progn\u00f3stico<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Terapia de primeira linha<\/strong><br>Combina\u00e7\u00e3o de&nbsp;<strong>R-CHOP<\/strong>&nbsp;(rituximab, ciclofosfamida, doxorrubicina, vincristina, prednisona) e&nbsp;<strong>Irradia\u00e7\u00e3o<\/strong>&nbsp;do mediastino<br>frequentemente complementado por&nbsp;<strong>Etoposido<\/strong>&nbsp;(por exemplo, programas de refer\u00eancia R-CHOP Plus).<\/li>\n\n\n\n<li><strong>Recorrente\/refrat\u00e1rio<\/strong><br>Inibidores PD-1 (por exemplo.&nbsp;<strong>Pembrolizumab<\/strong>,&nbsp;<strong>Nivolumab<\/strong>) est\u00e3o estabelecidos e prontos para autoriza\u00e7\u00e3o<br><strong>Brentuximab vedotina<\/strong>&nbsp;(conjugado anticorpo-f\u00e1rmaco anti-CD30) e&nbsp;<strong>Terapias com c\u00e9lulas T CAR<\/strong>&nbsp;(por exemplo.&nbsp;&nbsp;<strong>Axicabtagen Ciloleucel<\/strong>) oferecem op\u00e7\u00f5es promissoras na segunda e terceira linhas<\/li>\n\n\n\n<li><strong>Remiss\u00e3o a longo prazo<\/strong><br>Com a terapia inicial, o&nbsp;<strong>Taxa de sobreviv\u00eancia superior a 90 %<\/strong><br>Mau progn\u00f3stico em caso de recorr\u00eancia ou refractariedade&nbsp;<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-6\"><\/span>Diagn\u00f3stico diferencial<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Os diagn\u00f3sticos diferenciais importantes s\u00e3o<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Linfoma de Hodgkin cl\u00e1ssico<\/strong>&nbsp;(perfis moleculares semelhantes, mas tipos de c\u00e9lulas diferentes)<\/li>\n\n\n\n<li><strong>Linfoma difuso de grandes c\u00e9lulas B (DLBCL, NOS)<\/strong><\/li>\n\n\n\n<li><strong>Linfoma de c\u00e9lulas B de alto grau (HGBL)<\/strong>&nbsp;com rearranjo MYC e BCL2 (\u201elinfoma de duplo efeito\u201c)<\/li>\n\n\n\n<li><strong>Carcinoma do timo<\/strong>&nbsp;ou&nbsp;<strong>Timoma<\/strong>&nbsp;(especialmente no mediastino)<\/li>\n\n\n\n<li><strong>Met\u00e1stases de g\u00e2nglios linf\u00e1ticos de outros tumores<\/strong>&nbsp;(por exemplo, carcinoma dos br\u00f4nquios)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">A demarca\u00e7\u00e3o \u00e9 efectuada por&nbsp;<strong>Imunohistoqu\u00edmica<\/strong>,&nbsp;<strong>an\u00e1lises citogen\u00e9ticas<\/strong>&nbsp;(por exemplo, FISH para amplifica\u00e7\u00e3o de 9p24.1) e&nbsp;<strong>An\u00e1lises do transcriptoma<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">O PMBCL \u00e9 um linfoma agressivo de c\u00e9lulas B raro, mas facilmente trat\u00e1vel, com localiza\u00e7\u00e3o carater\u00edstica no mediastino, sintomas cl\u00ednicos t\u00edpicos e um perfil molecular espec\u00edfico que&nbsp;<strong>Terapias direcionadas<\/strong>&nbsp;como&nbsp;<strong>Inibidores PD-1<\/strong>&nbsp;e&nbsp;<strong>C\u00e9lulas CAR-T<\/strong>&nbsp;tornada poss\u00edvel.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"BL\"><span class=\"ez-toc-section\" id=\"Burkitt-Lymphom_BL\"><\/span><strong>Linfoma de Burkitt (BL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">O linfoma de Burkitt (BL) \u00e9 um linfoma n\u00e3o-Hodgkin de c\u00e9lulas B altamente maligno e agressivo com&nbsp;<strong>taxa de divis\u00e3o celular extraordinariamente elevada<\/strong>&nbsp;e uma taxa de prolifera\u00e7\u00e3o de quase 100 1TP3.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_Merkmale-6\"><\/span><strong>Carater\u00edsticas cl\u00ednicas<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Morfologicamente, apresenta uma&nbsp;<strong>Infiltrado difuso, puramente bl\u00e1stico<\/strong>&nbsp;de c\u00e9lulas de tamanho m\u00e9dio com&nbsp;<strong>n\u00facleos redondos e bas\u00f3filos<\/strong>,&nbsp;<strong>v\u00e1rios nucl\u00e9olos<\/strong>&nbsp;e um&nbsp;<strong>citoplasma bas\u00f3filo carater\u00edstico, com vacuoliza\u00e7\u00e3o<\/strong>.  Uma carater\u00edstica histol\u00f3gica t\u00edpica \u00e9 a&nbsp;<strong>\u201ePadr\u00e3o \u201cC\u00e9u estrelado<\/strong>, gerado por&nbsp;<strong>macr\u00f3fagos de cor clara<\/strong>, que fagocitam c\u00e9lulas tumorais apopt\u00f3ticas.  Clinicamente, distinguem-se tr\u00eas variantes:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>BL end\u00e9mica<\/strong>Comum em \u00c1frica, Brasil e Papua-Nova Guin\u00e9; principalmente na&nbsp;<strong>Ossos do maxilar ou da face<\/strong>&nbsp;manifestou-se, sobretudo em crian\u00e7as.&nbsp;&nbsp;<strong>&gt;95 % associado ao EBV<\/strong><\/li>\n\n\n\n<li><strong>BL espor\u00e1dico<\/strong>Em todo o mundo, especialmente em crian\u00e7as e jovens adultos; t\u00edpico&nbsp;<strong>manifesta\u00e7\u00e3o abdominal<\/strong>&nbsp;(v\u00e1lvula ileocecal, mesent\u00e9rio), pode levar \u00e0 obstru\u00e7\u00e3o intestinal.&nbsp;&nbsp;<strong>~20 % associado ao EBV<\/strong><\/li>\n\n\n\n<li><strong>Les\u00e3o associada \u00e0 imunodefici\u00eancia<\/strong>Comum na infe\u00e7\u00e3o pelo VIH (doen\u00e7a definidora de SIDA), com&nbsp;<strong>participa\u00e7\u00e3o nodal<\/strong>&nbsp;e&nbsp;<strong>Infiltra\u00e7\u00e3o da medula \u00f3ssea<\/strong><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-7\"><\/span><strong>Diagn\u00f3stico diferencial<\/strong>tique<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Linfoma de c\u00e9lulas B de alto grau (HGBL) com transloca\u00e7\u00f5es MYC e BCL2 e\/ou BCL6<\/strong><br>(linfoma de \u201eduplo golpe\u201c)<br>sobrep\u00f5e-se cl\u00ednica e biologicamente \u00e0 BL<br><strong>Pior progn\u00f3stico<\/strong><\/li>\n\n\n\n<li><strong>Leucemia linfobl\u00e1stica aguda (LLA) Forma L3<\/strong><br>(leucemia de Burkitt), se houver envolvimento da medula \u00f3ssea &gt;25 %<\/li>\n\n\n\n<li><strong>Linfoma difuso de grandes c\u00e9lulas B (DLBCL)<\/strong><br>especialmente com o rearranjo MYC, mas sem a gen\u00e9tica e a morfologia t\u00edpicas da BL<\/li>\n\n\n\n<li><strong>Doen\u00e7as linfoproliferativas em doentes imunocomprometidos<\/strong>&nbsp;<br>(por exemplo, ap\u00f3s um transplante)<br>podem apresentar padr\u00f5es semelhantes associados ao EBV<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methoden-5\"><\/span><strong>M\u00e9todos de diagn\u00f3stico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Citomorfologia<\/strong><br>O esfrega\u00e7o da medula \u00f3ssea e a biopsia de tecido mostram c\u00e9lulas bl\u00e1sticas carater\u00edsticas com um padr\u00e3o de \u201ec\u00e9u estrelado\u201c<\/li>\n\n\n\n<li><strong>Imunofenotipagem<\/strong><br>Positivo para&nbsp;<strong>CD19, CD20, CD10, CD38, CD43, CD81, FMC-7, MYC<\/strong><br>Negativo para&nbsp;<strong>BCL2, CD44, TdT, CD34<\/strong><\/li>\n\n\n\n<li><strong>An\u00e1lise cromoss\u00f3mica<\/strong><br>Prova da&nbsp;<strong>Transloca\u00e7\u00e3o t(8;14)(q24;q32)<\/strong>&nbsp;(85 %), mais raramente t(2;8) ou t(8;22)<\/li>\n\n\n\n<li><strong>PEIXE<\/strong><br>Por defeito&nbsp;<strong>Rearranjo MYC<\/strong>&nbsp;(com IGH::MYC* ou sonda independente de MYC).&nbsp;&nbsp;<strong>Sonda 11q23\/11q24<\/strong>&nbsp;ajuda a diferenciar contra HGBL11q<br>* Nota\u00e7\u00e3o gen\u00e9tica molecular \u201e::\u201c para indicar um&nbsp;<strong>Fus\u00e3o ou rearranjo de genes<\/strong> para simbolizar;<br>aqui a fus\u00e3o do oncogene MYC com o gene IGH<\/li>\n\n\n\n<li><strong>Gen\u00e9tica molecular<\/strong>Muta\u00e7\u00f5es em&nbsp;<strong>ID3, MYC, TP53, FOXO1<\/strong>&nbsp;(especialmente com BL EBV-negativa)<\/li>\n\n\n\n<li><strong>Imagiologia<\/strong>:&nbsp;<strong>PET-CT<\/strong>&nbsp;(capta\u00e7\u00e3o elevada de FDG),&nbsp;<strong>RMN<\/strong>&nbsp;com envolvimento do SNC<\/li>\n\n\n\n<li><strong>Exame do l\u00edquido cefalorraquidiano<\/strong>: Obrigat\u00f3rio devido \u00e0 elevada probabilidade de envolvimento do SNC<\/li>\n\n\n\n<li><strong>N\u00edvel de LDH<\/strong>:&nbsp;<strong>&gt;500 U\/L<\/strong>&nbsp;\u00e9 um fator de risco<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-6\"><\/span><strong>Terapia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O tratamento \u00e9&nbsp;<strong>emerg\u00eancia<\/strong>&nbsp;para iniciar:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Terapia de primeira linha<\/strong><br>Quimioterapia intensiva e curta com&nbsp;<strong>Rituximab<\/strong><br>(por exemplo.&nbsp;&nbsp;<strong>R-CODOX-M\/R-IVAC<\/strong>&nbsp;ou&nbsp;<strong>Protocolo GMALL-B-ALL\/NHL<\/strong>)<\/li>\n\n\n\n<li><strong>Profilaxia do SNC<\/strong><br>Intratecal e sist\u00e9mica&nbsp;<strong>Metotrexato<\/strong><\/li>\n\n\n\n<li><strong>Profilaxia da s\u00edndrome de lise tumoral<\/strong><br>Hidrata\u00e7\u00e3o intravenosa,&nbsp;<strong>Alopurinol ou rasburicase<\/strong>&nbsp;(contraindicado em caso de defici\u00eancia de G6PD!)<\/li>\n\n\n\n<li><strong>Terapia de resgate<\/strong><br>Em caso de recidiva ou de insucesso do tratamento&nbsp;<strong>Transplante aut\u00f3logo de c\u00e9lulas estaminais<\/strong>&nbsp;(perspectivas limitadas de sucesso)<\/li>\n\n\n\n<li><strong>Indica\u00e7\u00f5es raras<\/strong><br>Radioterapia ou interven\u00e7\u00e3o cir\u00fargica para sintomas complicados (por exemplo, obstru\u00e7\u00e3o intestinal).&nbsp;<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-5\"><\/span><strong>Previs\u00e3o<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Em&nbsp;<strong>pa\u00edses ricos em recursos<\/strong><br><strong>Sobreviv\u00eancia global &gt;80 % em adultos, &gt;90 % em crian\u00e7as<\/strong>&nbsp;sob imunoterapia moderna (por exemplo, com rituximab)<\/li>\n\n\n\n<li>Nos pa\u00edses com&nbsp;<strong>recursos reduzidos<\/strong><br>Progn\u00f3stico significativamente pior devido a atrasos no diagn\u00f3stico e no tratamento<\/li>\n\n\n\n<li><strong>BL-IPI (\u00cdndice Internacional de Progn\u00f3stico)<\/strong><br>Ajuda na avalia\u00e7\u00e3o do risco (por exemplo, LDH, est\u00e1dio, idade, envolvimento do SNC)<\/li>\n\n\n\n<li><strong>Subgrupos gen\u00e9ticos moleculares<\/strong><br>(por exemplo, com muta\u00e7\u00f5es TP53, ID3 ou FOXO1) influenciam o curso da doen\u00e7a<\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"LBL\"><span class=\"ez-toc-section\" id=\"Lymphoblastisches_Lymphom_BL\"><\/span>Linfoma linfobl\u00e1stico (BL)<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial do linfoma linfobl\u00e1stico (LB) requer uma diferencia\u00e7\u00e3o cuidadosa de outras neoplasias de c\u00e9lulas B, em particular&nbsp;<strong>Linfoma de Burkitt (BL)<\/strong>a&nbsp;<strong>linfoma difuso de grandes c\u00e9lulas B (DLBCL)<\/strong>&nbsp;e o&nbsp;<strong>Leucemia linfobl\u00e1stica aguda da linhagem B (B-ALL)<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">As carater\u00edsticas cl\u00ednicas morfol\u00f3gicas, imunofenot\u00edpicas e de gen\u00e9tica molecular s\u00e3o decisivas para a classifica\u00e7\u00e3o correta.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisch-morphologische_Merkmale-4\"><\/span><strong>Carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Citomorfologia<\/strong><br>No&nbsp;<strong>Linfoma de Burkitt<\/strong>&nbsp;as c\u00e9lulas apresentam formas bl\u00e1sticas de tamanho m\u00e9dio com&nbsp;<strong>citoplasma bas\u00f3filo profundo<\/strong>,&nbsp;<strong>vacuoliza\u00e7\u00e3o carater\u00edstica<\/strong>,&nbsp;<strong>n\u00facleos redondos<\/strong>&nbsp;e&nbsp;<strong>v\u00e1rios nucl\u00e9olos bas\u00f3filos<\/strong><br>A taxa de divis\u00e3o celular \u00e9 extremamente elevada.<\/li>\n\n\n\n<li><strong>Tamanho da c\u00e9lula e citoplasma da c\u00e9lula<\/strong><br>Em contraste com as c\u00e9lulas B-ALL, as c\u00e9lulas em BL&nbsp;<strong>n\u00e3o pequeno<\/strong>, mas de tamanho m\u00e9dio, e mostram&nbsp;<strong>sem altera\u00e7\u00f5es significativas do citoplasma celular<\/strong>&nbsp;tal como acontece com o ALL<\/li>\n\n\n\n<li><strong>\u00cdndice de prolifera\u00e7\u00e3o<\/strong><br><strong>Ki67 &gt; 95%<\/strong>&nbsp;- um marcador central para a elevada prolifera\u00e7\u00e3o celular em BL<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-8\"><\/span><strong>Diagn\u00f3stico diferencial<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Comparado com B-ALL<\/strong><br><strong>- Aus\u00eancia de express\u00e3o de marcadores imaturos<\/strong>BL \u00e9&nbsp;<strong>CD34- e TdT-negativo<\/strong>,<br>enquanto B-ALL&nbsp;<strong>CD34+ e TdT+<\/strong>&nbsp;\u00e9<\/li>\n\n\n\n<li>- <strong>Express\u00e3o da cadeia leve<\/strong>Programas BL&nbsp;<strong>express\u00e3o concentrada da cadeia ligeira (kappa\/lambda)<\/strong>,<br>o que falta na B-ALL<\/li>\n\n\n\n<li><strong>Comparado com DLBCL<\/strong><br>- <strong>Rearranjo MYC<\/strong>: O BL \u00e9&nbsp;<strong>Transloca\u00e7\u00e3o MYC (t(8;14), t(8;22), t(2;8))<\/strong>&nbsp;central, <br>mas&nbsp;<strong>n\u00e3o espec\u00edfico<\/strong>&nbsp;- tamb\u00e9m ocorre com DLBCL<br>- <strong>Cari\u00f3tipo<\/strong>Programas BL&nbsp;<strong>cari\u00f3tipos menos complexos<\/strong>&nbsp;como DLBCL<br>- <strong>Imunofen\u00f3tipo<\/strong><br>BL \u00e9&nbsp;<strong>CD10+, CD19+, CD20+, CD38+++, CD81+++, CD43+, MYC+++<\/strong>, mas&nbsp;<strong>BCL2-, CD5-, CD44-, CD138-<\/strong><\/li>\n\n\n\n<li><strong>Comparado com HGBL com aberra\u00e7\u00f5es 11q<\/strong><br>A entidade&nbsp;<strong>HGBL com aberra\u00e7\u00e3o 11q (HGBL11q)<\/strong>&nbsp;foi redefinido pela OMS em 2022 e caracteriza-se por&nbsp;<strong>11q23\/11q24-Ver\u00e4nderungen<\/strong>&nbsp;de<br>Difere molecularmente da LN cl\u00e1ssica (por exemplo, devido a muta\u00e7\u00f5es em&nbsp;<strong>ID3, TP53, FOXO1<\/strong>)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methoden-6\"><\/span><strong>M\u00e9todos de diagn\u00f3stico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Citomorfologia<\/strong>&nbsp;- Obrigat\u00f3rio<\/li>\n\n\n\n<li><strong>Imunofenotipagem (citometria de fluxo)<\/strong><br><strong>EDTA ou heparina<\/strong>&nbsp;como anticoagulante.  Dete\u00e7\u00e3o de&nbsp;<strong>CD19+, CD20+, CD10+, CD38++, CD81+++, CD43+, MYC+++<\/strong>,&nbsp;<strong>BCL2-<\/strong><\/li>\n\n\n\n<li><strong>PEIXE<\/strong> - Obrigat\u00f3rio<br>Prova de&nbsp;<strong>Rearranjos MYC<\/strong>&nbsp;(sonda IG::MYC) e&nbsp;<strong>Aberra\u00e7\u00f5es 11q<\/strong>&nbsp;(sonda 11q23\/24)<br>Distin\u00e7\u00e3o entre&nbsp;<strong>BL, HGBL11q e DLBCL\/HGBL-MYC\/BCL2<\/strong><\/li>\n\n\n\n<li><strong>Gen\u00e9tica molecular<\/strong><br>An\u00e1lise de&nbsp;<strong>ID3, TP53, FOXO1, MYC<\/strong>.&nbsp;<strong>Rearranjo BCL2 em falta<\/strong>&nbsp;com BL<br>em contraste com o HGBL<\/li>\n\n\n\n<li><strong>An\u00e1lise cromoss\u00f3mica<\/strong><br><strong>Heparina<\/strong>&nbsp;(como anticoagulante para a cultura) recomendado, confirma\u00e7\u00e3o de altera\u00e7\u00f5es complexas<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-7\"><\/span><strong>Terapia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Terapia padr\u00e3o<\/strong><br><strong>Imunoquimioterapia intensiva<\/strong>&nbsp;(por exemplo.&nbsp;&nbsp;<strong>R-CODOX-M\/IVAC<\/strong>,&nbsp;<strong>DA-EPOCH-R<\/strong>) com&nbsp;<strong>Rituximab<\/strong><\/li>\n\n\n\n<li><strong>Profilaxia do SNC<\/strong><br><strong>Necess\u00e1rio<\/strong>&nbsp;devido ao elevado envolvimento do SNC<\/li>\n\n\n\n<li><strong>Terapias direcionadas<\/strong><br>Investigado em estudos cl\u00ednicos:&nbsp;<strong>Inibidores da BCL2 (venetoclax)<\/strong>,&nbsp;<strong>Inibidores da BTK (ibrutinib)<\/strong>,&nbsp;<strong>Inibidores de BCL6<\/strong>,&nbsp;<strong>Inibidores da PI3K<\/strong><\/li>\n\n\n\n<li><strong>Transplante de c\u00e9lulas estaminais<\/strong><br>Para casos de recorr\u00eancia ou de alto risco<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-6\"><\/span><strong>Previs\u00e3o<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Adultos<\/strong><br><strong>Sobreviv\u00eancia global &gt; 80%<\/strong>&nbsp;na terapia moderna em pa\u00edses ricos em recursos.<\/li>\n\n\n\n<li><strong>Crian\u00e7as<\/strong><br><strong>Acerca do 90%<\/strong>&nbsp;Sobreviv\u00eancia em 5 anos.&nbsp;<\/li>\n\n\n\n<li><strong>Factores de progn\u00f3stico<\/strong>:<br>- <strong>BL-IPI (\u00cdndice Internacional de Progn\u00f3stico do Linfoma de Burkitt)<\/strong>Tem em conta a idade, o est\u00e1dio, a LDH, o estado geral, o envolvimento extranodal<br>- <strong>Subgrupos moleculares<\/strong> -&nbsp;<strong>BL negativo para EBV<\/strong>&nbsp;com&nbsp;<strong>Muta\u00e7\u00f5es TP53 ou ID3<\/strong>&nbsp;apresenta um pior progn\u00f3stico<br>- <strong>Envolvimento do SNC<\/strong>&nbsp;e&nbsp;<strong>LDH elevada<\/strong>&nbsp;s\u00e3o factores desfavor\u00e1veis<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico correto requer um&nbsp;<strong>abordagem integrada<\/strong>&nbsp;de&nbsp;<strong>Morfologia, imunofenotipagem, FISH e gen\u00e9tica molecular<\/strong>, para diferenciar o linfoma de Burkitt de outros linfomas agressivos de c\u00e9lulas B e permitir uma terapia precisa.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"PKDGBZL\"><span class=\"ez-toc-section\" id=\"Primar_kutanes_diffus_groszelliges_B-Zell-Lymphom_Beintyp_DLBCL_LT\"><\/span>Linfoma cut\u00e2neo prim\u00e1rio difuso de grandes c\u00e9lulas B, tipo perna (DLBCL, LT)<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>Linfoma cut\u00e2neo prim\u00e1rio difuso de grandes c\u00e9lulas B, tipo perna (DLBCL, LT)<\/strong> \u00e9 um&nbsp;<strong>Linfoma cut\u00e2neo prim\u00e1rio agressivo com mau progn\u00f3stico<\/strong>, que se caracteriza por&nbsp;<strong>carater\u00edsticas cl\u00ednicas, histol\u00f3gicas e biol\u00f3gicas moleculares espec\u00edficas<\/strong>&nbsp;e manifesta-se sobretudo nas pernas.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico requer um&nbsp;<strong>Diagn\u00f3sticos de propaga\u00e7\u00e3o abrangentes<\/strong>, e a terapia baseia-se em&nbsp;<strong>R-CHOP<\/strong>&nbsp;de s\u00e9rie.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">O progn\u00f3stico \u00e9 moderado apesar da terapia, raz\u00e3o pela qual \u00e9 crucial um tratamento precoce e intensivo.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Difere em termos cl\u00ednicos, histol\u00f3gicos e de progn\u00f3stico das formas indolentes, como o linfoma cut\u00e2neo prim\u00e1rio da zona marginal (PCMZL) ou o linfoma cut\u00e2neo prim\u00e1rio do centro germinativo (PCFCL).<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_Merkmale-7\"><\/span>Carater\u00edsticas cl\u00ednicas<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Localiza\u00e7\u00e3o<\/strong><br>Tipicamente&nbsp;<strong>individualmente ou em grupo, numa ou em ambas as pernas<\/strong><\/li>\n\n\n\n<li><strong>Apar\u00eancia<\/strong><br><strong>Tumores escuros eritematosos a l\u00edvidos, duros e endurecidos<\/strong>, que se apresentam como placas ou n\u00f3dulos<\/li>\n\n\n\n<li><strong>Curso<\/strong><br>Agressivo, com&nbsp;<strong>taxa de crescimento r\u00e1pido<\/strong>&nbsp;e elevado risco de recorr\u00eancia<\/li>\n\n\n\n<li><strong>Sintomas sist\u00e9micos<\/strong><br>Em fases avan\u00e7adas, podem ocorrer sintomas B (febre, suores noturnos, perda de peso)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisch-morphologische_Merkmale-5\"><\/span>Carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Histologia<\/strong><br>Infiltrados difusos de c\u00e9lulas B grandes e maduras com&nbsp;<strong>carater\u00edsticas nucleares, tais como c\u00e9lulas de grandes dimens\u00f5es, nucl\u00e9olos grandes e numerosas mitoses<\/strong>.&nbsp;<\/li>\n\n\n\n<li><strong>Imunohistoqu\u00edmica<\/strong>e<br>- <strong>Positivo para<\/strong> CD20, CD79a, CD10 (em partes), Bcl-6, MUM1\/IRF4<br>- <strong>Negativo para<\/strong> CD5, CD10 (geralmente), Bcl-2 (geralmente negativo, em contraste com DLBCL sist\u00e9mico)&nbsp;<\/li>\n\n\n\n<li><strong>Biologia molecular<\/strong><br>Muta\u00e7\u00f5es frequentes em&nbsp;<strong>Bcl-2, MYD88, MALT-1, Myc e INK4<\/strong>, que promove a resist\u00eancia \u00e0 morte celular e a desregula\u00e7\u00e3o do ciclo celular.<br>No entanto, a patog\u00e9nese ainda n\u00e3o \u00e9 totalmente compreendida<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-9\"><\/span>Diagn\u00f3stico diferencial<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial \u00e9 crucial, uma vez que o DLBCL, LT pode ser cl\u00ednica e histologicamente confundido com outros tumores cut\u00e2neos ou doen\u00e7as linfoproliferativas:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Pseudolinfomas reactivos de c\u00e9lulas B<\/strong><br>Imagens histol\u00f3gicas semelhantes, mas&nbsp;<strong>Sem rearranjo clonal de imunoglobulinas<\/strong>, sem envolvimento sist\u00e9mico<\/li>\n\n\n\n<li><strong>DLBCL sist\u00e9mico com envolvimento prim\u00e1rio da pele<\/strong><br>Deve passar por&nbsp;<strong>Diagn\u00f3stico de propaga\u00e7\u00e3o<\/strong>&nbsp;(TC, PET-CT, medula \u00f3ssea) podem ser exclu\u00eddos<\/li>\n\n\n\n<li><strong>Outros linfomas cut\u00e2neos<\/strong><br>DLBCL, a LT deve ser obtida de&nbsp;<strong>PCFCL<\/strong>,&nbsp;<strong>PCMZL<\/strong>&nbsp;e&nbsp;<strong>linfoma intravascular de grandes c\u00e9lulas B<\/strong>&nbsp;ser delimitado<\/li>\n\n\n\n<li><strong>Outros tumores malignos da pele<\/strong><br>O melanoma, o carcinoma e o sarcoma s\u00e3o diferenciados por imunohistoqu\u00edmica (por exemplo, S100, HMB-45, desmina)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methoden-7\"><\/span>M\u00e9todos de diagn\u00f3stico<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Bi\u00f3psia<\/strong><br><strong>Bi\u00f3psia de amostra suficientemente grande e n\u00e3o traum\u00e1tica<\/strong>&nbsp;para exames histol\u00f3gicos, imunohistoqu\u00edmicos e de biologia molecular<\/li>\n\n\n\n<li><strong>Imunohistoqu\u00edmica<\/strong><br>Prova de&nbsp;<strong>CD20, CD79a, Bcl-6, MUM1\/IRF4<\/strong>, exclus\u00e3o de CD5, CD10<\/li>\n\n\n\n<li><strong>Biologia molecular<\/strong><br>Prova de um&nbsp;<strong>rearranjo clonal da cadeia pesada de imunoglobulina<\/strong><\/li>\n\n\n\n<li><strong>Diagn\u00f3stico de propaga\u00e7\u00e3o<\/strong><br>- <strong>Qu\u00edmica laboratorial<\/strong> - Hemograma, fun\u00e7\u00e3o hep\u00e1tica e renal, LDH<br>- <strong>Imagiologia<\/strong> - <strong>PET-CT<\/strong>&nbsp;ou&nbsp;<strong>TC<\/strong>&nbsp;do t\u00f3rax, do abd\u00f3men e da p\u00e9lvis<br>- <strong>Bi\u00f3psia da medula \u00f3ssea<\/strong> - <strong>Obrigat\u00f3rio para DLBCL, LT<\/strong>&nbsp;devido \u00e0 trajet\u00f3ria agressiva<br>- <strong>Exame dos g\u00e2nglios linf\u00e1ticos<\/strong> - G\u00e2nglios linf\u00e1ticos cervicais e axilares&nbsp;<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-8\"><\/span>Terapia<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Terapia de primeira linha<\/strong><br><strong>Esquema R-CHOP<\/strong>&nbsp;(rituximab, ciclofosfamida, doxorrubicina, vincristina, prednisona)<\/li>\n\n\n\n<li><strong>alternativa<\/strong><br>Outras poliquimioterapias com rituximab, se necess\u00e1rio&nbsp;<strong>Transplante de c\u00e9lulas estaminais<\/strong>&nbsp;Em caso de recidiva ou de doen\u00e7a resistente \u00e0 terap\u00eautica<\/li>\n\n\n\n<li><strong>Terapia local<\/strong><br>Para les\u00f5es solit\u00e1rias -&nbsp;<strong>Radioterapia<\/strong>&nbsp;ou&nbsp;<strong>Excis\u00e3o total<\/strong>, mas apenas como&nbsp;<strong>Adjun\u00e7\u00e3o<\/strong>, n\u00e3o apenas para DLBCL, LT<\/li>\n\n\n\n<li><strong>Terapia sist\u00e9mica<\/strong><br>Para les\u00f5es m\u00faltiplas ou disseminadas - <strong>rituximab intravenoso<\/strong>&nbsp;em combina\u00e7\u00e3o com quimioterapia<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-7\"><\/span>Previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Taxa de sobreviv\u00eancia a 5 anos<\/strong><br><strong>aprox. 55 %<\/strong>&nbsp;- significativamente pior do que nas formas indolentes<\/li>\n\n\n\n<li><strong>Factores de progn\u00f3stico desfavor\u00e1vel<\/strong><br>Idade &gt; 60 anos, LDH elevada, envolvimento da medula \u00f3ssea, est\u00e1dios tumorais elevados (T3\/T4), aus\u00eancia de express\u00e3o de CD10<\/li>\n\n\n\n<li><strong>Taxa de recorr\u00eancia<\/strong><br>Elevado,&nbsp;<strong>40-50 % dos doentes sofrem recorr\u00eancias<\/strong><\/li>\n\n\n\n<li><strong>Cuidados posteriores<\/strong><br>Controlos regulares (por exemplo, de 3 em 3 meses nos primeiros 3 anos e depois de 6 em 6 meses) com exames cl\u00ednicos, laboratoriais e imagiol\u00f3gicos, se necess\u00e1rio<\/li>\n<\/ul>\n\n\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"GrauzonenGrenzfalle-2\"><\/span><strong>\u00c1reas cinzentas\/casos-limite<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"BLu\"><span class=\"ez-toc-section\" id=\"Diffus_groszelliges_B-Zell-Lymphom_NOS_DLBCL_NOS_und_Burkitt-Lymphom_BL\"><\/span><strong>Linfoma difuso de grandes c\u00e9lulas B, NOS (DLBCL, NOS)<\/strong>&nbsp;e&nbsp;<strong>Linfoma de Burkitt (BL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O <strong>Linfoma difuso de grandes c\u00e9lulas B, NOS (DLBCL, NOS)<\/strong>&nbsp;e&nbsp;<strong>Linfoma de Burkitt (BL)<\/strong>&nbsp;s\u00e3o ambos linfomas agressivos de c\u00e9lulas B com carater\u00edsticas morfol\u00f3gicas e imunofenot\u00edpicas que se sobrep\u00f5em, o que exige uma diferencia\u00e7\u00e3o precisa.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A atual classifica\u00e7\u00e3o 2022 da OMS clarificou a diferencia\u00e7\u00e3o ao definir marcadores gen\u00e9ticos espec\u00edficos como decisivos para a classifica\u00e7\u00e3o.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_und_morphologisches_Bild\"><\/span>Quadro cl\u00ednico e morfol\u00f3gico<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>DLBCL, NOS<\/strong><br>Normalmente, mostra um&nbsp;<strong>Infiltra\u00e7\u00e3o difusa de c\u00e9lulas grandes<\/strong>&nbsp;com c\u00e9lulas centrobl\u00e1sticas, imunobl\u00e1sticas ou anapl\u00e1sicas<br>As c\u00e9lulas s\u00e3o de tamanho m\u00e9dio a grande, com cromatina frouxa e nucl\u00e9olos distintos.&nbsp;<strong>Necrose<\/strong>&nbsp;s\u00e3o frequentemente<br>O quadro cl\u00ednico inclui envolvimento dos g\u00e2nglios linf\u00e1ticos, infiltra\u00e7\u00e3o do ba\u00e7o e da medula \u00f3ssea, bem como sintomas B (febre, suores noturnos, perda de peso)<br>As manifesta\u00e7\u00f5es extranodais n\u00e3o s\u00e3o invulgares<\/li>\n\n\n\n<li><strong>Linfoma de Burkitt<\/strong><br>Caracterizado por um&nbsp;<strong>Taxa de prolifera\u00e7\u00e3o extremamente elevada<\/strong>&nbsp;(Ki67 &gt;95 %), um&nbsp;<strong>\u201ePadr\u00e3o do c\u00e9u estrelado<\/strong>&nbsp;devido a macr\u00f3fagos na massa tumoral e&nbsp;<strong>Explos\u00f5es pequenas e homog\u00e9neas<\/strong>&nbsp;com pouco citoplasma<br>Ocorre frequentemente de forma extranodal (por exemplo, na cavidade abdominal, medula \u00f3ssea, SNC) e est\u00e1 associada a uma progress\u00e3o r\u00e1pida e com risco de vida<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_Methodik\"><\/span>Diagn\u00f3stico diferencial e metodologia<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">A diferencia\u00e7\u00e3o baseia-se numa&nbsp;<strong>diagn\u00f3stico multimodal<\/strong>, pois existem semelhan\u00e7as morfol\u00f3gicas:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Citomorfologia e Histologia<\/strong><br>O&nbsp;<strong>Citomorfologia<\/strong>&nbsp;\u00e9 o primeiro passo.<br>A BL apresenta normalmente&nbsp;<strong>Explos\u00f5es pequenas e homog\u00e9neas<\/strong>, enquanto o DLBCL, NOS tem c\u00e9lulas maiores e heterog\u00e9neas.<br>O&nbsp;<strong>Citologia da medula \u00f3ssea<\/strong>&nbsp;\u00e9 essencial, uma vez que as infiltra\u00e7\u00f5es podem ser discordantes do envolvimento dos g\u00e2nglios linf\u00e1ticos.&nbsp;<\/li>\n\n\n\n<li><strong>Imunofenotipagem (imunohistoqu\u00edmica)<\/strong><br>- <strong>DLBCL, NOS<\/strong><br>Positivo para&nbsp;<strong>CD20, CD19, CD79a, PAX5, CD10 (30-50 %)<\/strong>,&nbsp;<strong>BCL6 (75-89 %)<\/strong>,&nbsp;<strong>MUM1\/IRF4 (17-42 %)<\/strong><br><strong>BCL2<\/strong>&nbsp;e&nbsp;<strong>MYC<\/strong>&nbsp;s\u00e3o expressos em muitos casos (fen\u00f3tipo de \u201eduplo expressor\u201c)<br>- <strong>Linfoma de Burkitt<\/strong><br>Positivo para&nbsp;<strong>CD20, CD19, CD79a, PAX5, CD10, BCL6, CD56, LMO2<\/strong><br><strong>BCL2 negativo<\/strong><br><strong>MYC fortemente expresso<\/strong><br><strong>TdT positivo<\/strong>&nbsp;em at\u00e9 2 % dos casos<\/li>\n\n\n\n<li><strong>Diagn\u00f3stico gen\u00e9tico e molecular<\/strong><br>- <strong>FISH (hibrida\u00e7\u00e3o in situ por fluoresc\u00eancia)<\/strong><br>a diferen\u00e7a decisiva:<br>\u2013 \u2013 <strong>DLBCL, NOS<\/strong><br>\u2013 \u2013 \u2013 <strong>Sem rearranjo MYC-BCL2<\/strong><br>\u2013 \u2013 \u2013 <strong>Rearranjo MYC isolado<\/strong>&nbsp;(at\u00e9 14 %) \u00e9 poss\u00edvel, mas n\u00e3o h\u00e1 indica\u00e7\u00e3o de BL<br>\u2013 \u2013 <strong><strong>Linfoma de Burkitt<\/strong><\/strong><br>\u2013 \u2013 \u2013 <strong><strong>Transloca\u00e7\u00e3o t\u00edpica t(8;14)(q24;q32)<\/strong>&nbsp;\u2192&nbsp;<strong>Transloca\u00e7\u00e3o MYC com IGH<\/strong><\/strong><br>\u2013 \u2013 \u2013 <strong>Al\u00e9m disso, um&nbsp;<strong>transloca\u00e7\u00e3o dupla (t(8;14);t(2;8))<\/strong>&nbsp;ocorrer<\/strong><br>- <strong>An\u00e1lise da express\u00e3o gen\u00e9tica (padr\u00e3o de excel\u00eancia para COO)<\/strong><br>Utilizado para determinar o&nbsp;<strong>C\u00e9lula de origem (COO)<\/strong>-subtipo (GCB vs. ABC), mas&nbsp;<strong>N\u00e3o \u00e9 uma presta\u00e7\u00e3o normal das companhias de seguros de sa\u00fade<\/strong><br>O subtipo GCB tem genes semelhantes aos das c\u00e9lulas B do centro germinal, o subtipo ABC assemelha-se \u00e0s c\u00e9lulas B activadas<br>- <strong>Gen\u00e9tica molecular<\/strong><br>BL apresenta muta\u00e7\u00f5es t\u00edpicas em&nbsp;<strong>ID3, CCND3, TP53<\/strong><br>O DLBCL, NOS apresenta frequentemente&nbsp;<strong>CREBBP, EZH2, KMT2D, TP53<\/strong>&nbsp;sobre<\/li>\n\n\n\n<li><strong>Diferencia\u00e7\u00e3o dos linfomas de c\u00e9lulas B de alto grau (HGBL)<\/strong><br>- <strong>HGBL com rearranjo MYC e BCL2 (\u201edouble-hit\u201c)<\/strong><br>\u00c9&nbsp;<strong>j\u00e1 n\u00e3o faz parte de DLBCL, NOS<\/strong>, mas uma entidade distinta.<br><strong>Previs\u00e3o desfavor\u00e1vel<\/strong><br>requer terapia intensiva<br>- <strong>HGBL com aberra\u00e7\u00e3o 11q<\/strong><br><strong>Rearranjo MYC negativo<\/strong>, mas&nbsp;<strong>11q23.3 ganho e 11q24.1 qter perda<\/strong><br>A morfologia e o imunofen\u00f3tipo s\u00e3o semelhantes aos da BL, mas&nbsp;<strong>BCL2 negativo<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">UM&nbsp;<strong>hematopatologista experiente<\/strong>&nbsp;e&nbsp;<strong>Patologia de refer\u00eancia<\/strong>&nbsp;s\u00e3o recomendados!<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-9\"><\/span>Terapia<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>DLBCL, NOS<\/strong><br>A terapia padr\u00e3o \u00e9&nbsp;<strong>R-CHOP<\/strong>&nbsp;(rituximab, ciclofosfamida, doxorrubicina, vincristina, prednisona)<br>Com&nbsp;<strong>Recorr\u00eancia ou refractariedade<\/strong>&nbsp;s\u00e3o&nbsp;<strong>Terapias com c\u00e9lulas T CAR<\/strong>&nbsp;(por exemplo, Axicabtagene ciloleucel) autorizado<\/li>\n\n\n\n<li><strong>Linfoma de Burkitt<\/strong><br>Requer&nbsp;<strong>sess\u00f5es de quimioterapia intensivas e curtas<\/strong>&nbsp;(por exemplo.&nbsp;&nbsp;<strong>CODOX-M\/IVAC<\/strong>), uma vez que as c\u00e9lulas tumorais proliferam muito rapidamente<br><strong>Rituximab<\/strong>&nbsp;est\u00e1 integrado (R-CODOX-M\/IVAC)<br><strong>Profilaxia do SNC<\/strong>&nbsp;\u00e9 obrigat\u00f3rio<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-8\"><\/span>Previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>DLBCL, NOS<\/strong><br><strong>Taxa de sobreviv\u00eancia a 5 anos<\/strong><br>- com&nbsp;<strong>70-80 %<\/strong>&nbsp;(subtipo GCB)<br>- <strong>40-50 %<\/strong>&nbsp;(subtipo ABC)<br><strong>Fen\u00f3tipo de express\u00e3o dupla (MYC+BCL2)<\/strong>&nbsp;\u00e9 um fator desfavor\u00e1vel.&nbsp;<\/li>\n\n\n\n<li><strong>Linfoma de Burkitt<\/strong><br>Com&nbsp;<strong>Terapia intensiva<\/strong>&nbsp;\u00e9 alcan\u00e7ado&nbsp;<strong>Taxas de cicatriza\u00e7\u00e3o de at\u00e9 80-90 %<\/strong>, apesar de um percurso agressivo.&nbsp;<\/li>\n<\/ul>\n\n\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Spezielle_extranoduale_Lymphome-2\"><\/span><strong>Linfomas extranodais especiais<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"HSTL\"><span class=\"ez-toc-section\" id=\"Hepatosplenisches_Lymphom_HSTL\"><\/span><strong>Linfoma hepatoespl\u00e9nico<\/strong> (HSTL)<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Linfoma hepatoespl\u00e9nico de c\u00e9lulas T (HSTL)<\/strong>&nbsp;\u00e9 uma forma rara e agressiva de linfoma perif\u00e9rico de c\u00e9lulas T (PTCL), caracterizada por um envolvimento acentuado do f\u00edgado e do ba\u00e7o.  Ocorre geralmente na idade adulta e apresenta uma tr\u00edade cl\u00ednica t\u00edpica de&nbsp;<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Hepatoesplenomegalia<\/strong><\/li>\n\n\n\n<li><strong>Citopenias<\/strong><\/li>\n\n\n\n<li><strong>febre persistente<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico requer a diferencia\u00e7\u00e3o de outras doen\u00e7as com achados cl\u00ednicos e laboratoriais semelhantes.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_Merkmale-8\"><\/span>Carater\u00edsticas cl\u00ednicas<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Imagem cl\u00ednica<\/strong><br>A HSTL apresenta-se com&nbsp;<strong>Evolu\u00e7\u00e3o aguda e grave<\/strong>, frequentemente com febre, perda de peso, hepatoesplenomegalia e envolvimento de m\u00faltiplos \u00f3rg\u00e3os (por exemplo, disfun\u00e7\u00e3o hep\u00e1tica, di\u00e1tese hemorr\u00e1gica)<\/li>\n\n\n\n<li><strong>Citomorfologia<\/strong><br>As c\u00e9lulas do linfoma s\u00e3o&nbsp;<strong>Pequenas e m\u00e9dias empresas<\/strong>, com n\u00facleos irregulares e pouco citoplasma.  Apresentam uma infiltra\u00e7\u00e3o difusa na medula \u00f3ssea ou no ba\u00e7o<\/li>\n\n\n\n<li><strong>Imunofen\u00f3tipo<\/strong><br>As c\u00e9lulas expressam&nbsp;<strong>antig\u00e9nios pan-c\u00e9lulas T (CD2, CD3, CD5, CD7)<\/strong>&nbsp;e s\u00e3o&nbsp;<strong>CD4+ ou CD8+<\/strong>, frequentemente com&nbsp;<strong>dupla positividade (CD4+\/CD8+)<\/strong>.  Pode ocorrer uma perda de antig\u00e9nios das c\u00e9lulas T. A dete\u00e7\u00e3o de um&nbsp;<strong>Clonalidade<\/strong>&nbsp;por rearranjos do gene do recetor das c\u00e9lulas T (TZR) \u00e9 \u00fatil<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-10\"><\/span>Diagn\u00f3stico diferencial<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Linfohistiocitose hemofagoc\u00edtica prim\u00e1ria (HLH)<\/strong><br>Tamb\u00e9m se verificam febre, hepatoesplenomegalia, citopenia e hiperferritin\u00e9mia.&nbsp;<strong>A hemofagocitose na medula \u00f3ssea \u00e9 carater\u00edstica da HLH<\/strong>, mas n\u00e3o espec\u00edfico.  Este aspeto est\u00e1 normalmente ausente nas HSTL. O&nbsp;<strong>Crit\u00e9rios de diagn\u00f3stico de HLH (por exemplo, 5 de 8 crit\u00e9rios)<\/strong>&nbsp;devem ser cumpridos para excluir a HLH.&nbsp;<\/li>\n\n\n\n<li><strong>Doen\u00e7as sist\u00e9micas infecciosas<\/strong><br>A s\u00e9psis, as infec\u00e7\u00f5es virais (por exemplo, EBV, VIH), a tuberculose ou outras infec\u00e7\u00f5es podem causar sintomas semelhantes.&nbsp;<strong>EBV-PCR e EBER-ISH<\/strong>&nbsp;s\u00e3o importantes para a diferencia\u00e7\u00e3o, uma vez que a HSTL n\u00e3o est\u00e1 associada ao EBV.&nbsp;<\/li>\n\n\n\n<li><strong>Outros linfomas com envolvimento do f\u00edgado e do ba\u00e7o<\/strong>:\n<ul class=\"wp-block-list\">\n<li><strong>Linfoma difuso de grandes c\u00e9lulas B (DLBCL)<\/strong><br>maioritariamente CD20+, CD10+, BCL6+ <br>Normalmente sem fen\u00f3tipo CD4+\/CD8<\/li>\n\n\n\n<li><strong>Linfomas nodais de c\u00e9lulas auxiliares T-foliculares (linfomas nTFH)<\/strong><br>envolvimento cl\u00ednico semelhante, mas com&nbsp;<strong>CD10+, BCL6+, PD1+, CXCL13+<\/strong>&nbsp;e&nbsp;<strong>CD4+<\/strong>&nbsp;Fen\u00f3tipo<br>Em contraste com o HSTL, o linfoma nTFH \u00e9 frequentemente&nbsp;<strong>CD8-<\/strong><\/li>\n\n\n\n<li><strong>Linfoma anapl\u00e1sico de grandes c\u00e9lulas (ALCL)<\/strong><br>Pode ser CD30+, frequentemente com evolu\u00e7\u00e3o ALK-positiva ou ALK-negativa<br>Menor envolvimento do f\u00edgado e do ba\u00e7o<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>S\u00edndromes hemofagoc\u00edticas em doen\u00e7as auto-imunes<\/strong><br>No caso do l\u00fapus eritematoso sist\u00e9mico (LES) ou da artrite reumatoide juvenil (ARJ), um&nbsp;<strong>S\u00edndrome de ativa\u00e7\u00e3o dos macr\u00f3fagos (MAS)<\/strong>&nbsp;diferenciados por crit\u00e9rios cl\u00ednicos e laboratoriais.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methoden-8\"><\/span>M\u00e9todos de diagn\u00f3stico<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Citomorfologia e imunofenotipagem<\/strong><br>Obrigat\u00f3rio para a identifica\u00e7\u00e3o do fen\u00f3tipo das c\u00e9lulas T<\/li>\n\n\n\n<li><strong>FISH e gen\u00e9tica molecular<\/strong><br>Dete\u00e7\u00e3o de rearranjos TZR<br>Muta\u00e7\u00f5es em&nbsp;<strong>TP53<\/strong>,&nbsp;<strong>NOTCH2<\/strong>,&nbsp;<strong>KLF2<\/strong><\/li>\n\n\n\n<li><strong>EBER-ISH<\/strong><br>para excluir linfomas associados ao EBV (por exemplo, linfoma de c\u00e9lulas NK\/T)&nbsp;<\/li>\n\n\n\n<li><strong>Bi\u00f3psia<\/strong><br>Medula \u00f3ssea, ba\u00e7o ou g\u00e2nglios linf\u00e1ticos<br>para confirmar a infiltra\u00e7\u00e3o e a hemofagocitose, se presente<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie_und_Prognose-5\"><\/span>Terapia e progn\u00f3stico<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Terapia<\/strong><br>HSTL \u00e9 principalmente utilizado com&nbsp;<strong>protocolos imuno-quimioterap\u00eauticos<\/strong>&nbsp;tratados, por exemplo.&nbsp;&nbsp;<strong>CHOP<\/strong>&nbsp;ou&nbsp;<strong>EPOCH<\/strong>.<br>Em casos recorrentes ou refract\u00e1rios, o seguinte&nbsp;<strong>Transplantes de c\u00e9lulas estaminais<\/strong>&nbsp;em an\u00e1lise<\/li>\n\n\n\n<li><strong>Previs\u00e3o<\/strong><br><strong>Curso agressivo<\/strong>, sobreviv\u00eancia mediana inferior a 2 anos com terap\u00eautica inadequada, pior do que muitos outros subtipos de PTCL<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial da HSTL \u00e9 crucial, uma vez que a terap\u00eautica e o progn\u00f3stico dependem da entidade exacta. \u00c9 necess\u00e1ria uma colabora\u00e7\u00e3o estreita entre hematologistas, patologistas e imunologistas.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"IVGBL\"><span class=\"ez-toc-section\" id=\"Intravaszulares_groszelliges_B-Zell-Lymphom\"><\/span><strong>Linfoma intravascular de grandes c\u00e9lulas B<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Linfoma intravascular de grandes c\u00e9lulas B (IVBZL)<\/strong>&nbsp;\u00e9 uma forma rara e agressiva de linfoma difuso de grandes c\u00e9lulas B (DLBCL), caracterizada por&nbsp;<strong>prolifera\u00e7\u00e3o intravascular pura de linf\u00f3citos B malignos<\/strong>&nbsp;em vasos sangu\u00edneos de pequeno e m\u00e9dio porte de v\u00e1rios \u00f3rg\u00e3os, sem infiltra\u00e7\u00e3o significativa de linfonodos ou c\u00e9lulas tumorais circulantes.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_Merkmale-9\"><\/span>Carater\u00edsticas cl\u00ednicas<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Manifesta\u00e7\u00f5es cut\u00e2neas<\/strong><br>Eritema frequente, indistinto, reticular ou homog\u00e9neo, placas endurecidas, n\u00f3dulos subcut\u00e2neos (por vezes panicul\u00edticos), telangiectasias ou focos petequiais<br>As altera\u00e7\u00f5es cut\u00e2neas s\u00e3o frequentemente assintom\u00e1ticas, mas podem ser dolorosas<\/li>\n\n\n\n<li><strong>Sintomas sist\u00e9micos (sintomas B)<\/strong><br>Febre, suores noturnos, perda de peso, fadiga - ocorrem na maioria dos doentes, especialmente nos de origem asi\u00e1tica ou com doen\u00e7a avan\u00e7ada<\/li>\n\n\n\n<li><strong>Envolvimento do SNC<\/strong><br>Comum em doentes caucasianos: encefalopatias subagudas, crises epil\u00e9pticas, d\u00e9fices neurol\u00f3gicos, enfartes cerebrais, mielopatias, neuropatias perif\u00e9ricas<\/li>\n\n\n\n<li><strong>Infesta\u00e7\u00e3o de \u00f3rg\u00e3os<\/strong><br>Medula \u00f3ssea, ba\u00e7o, f\u00edgado (especialmente em pessoas de ascend\u00eancia asi\u00e1tica), pulm\u00f5es, cora\u00e7\u00e3o - conduz a sintomas relacionados com os \u00f3rg\u00e3os (por exemplo, falta de ar, insufici\u00eancia card\u00edaca)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostik\"><\/span>Diagn\u00f3stico<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Histologia<\/strong><br><strong>Linf\u00f3citos de c\u00e9lulas B estritamente intravasculares, pleom\u00f3rficos e altamente pleom\u00f3rficos<\/strong>&nbsp;com n\u00facleos redondos\/ovais, estanques \u00e0 cromatina<br>Os vasos est\u00e3o dilatados, frequentemente com trombos e dep\u00f3sitos fibrinosos<\/li>\n\n\n\n<li><strong>Imunohistoqu\u00edmica<\/strong><br>Positivo para&nbsp;<strong>CD20, CD79a, CD19<\/strong>, elevada taxa de prolifera\u00e7\u00e3o (Ki-67: 70-80 %).&nbsp;&nbsp;<strong>Negativo para marcadores endoteliais<\/strong>&nbsp;(por exemplo, CD31, CD34)<br>Sem express\u00e3o clonal de c\u00e9lulas T ou de c\u00e9lulas NK<\/li>\n\n\n\n<li><strong>Laborat\u00f3rio<\/strong><br>Anemia frequente (80-90 %), aumento da LDH, aumento da beta-2-microglobulina, trombocitopenia (65 %), leucopenia (25 %), aumento da velocidade de sedimenta\u00e7\u00e3o dos eritr\u00f3citos (43 %). Valores patol\u00f3gicos do f\u00edgado, dos rins e da tiroide a 15-20 %.&nbsp;<\/li>\n\n\n\n<li><strong>Imagiologia<\/strong><br>A resson\u00e2ncia magn\u00e9tica mostra les\u00f5es n\u00e3o espec\u00edficas (por exemplo, enfartes cerebrais m\u00faltiplos), que s\u00e3o frequentemente mal interpretadas<br>A PET-CT pode ser \u00fatil, mas sem especificidade<\/li>\n\n\n\n<li><strong>Confirma\u00e7\u00e3o histol\u00f3gica por biopsia de tecido<\/strong>&nbsp;de um \u00f3rg\u00e3o afetado (por exemplo, pele, c\u00e9rebro, medula \u00f3ssea)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-11\"><\/span>Diagn\u00f3stico diferencial<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Linfomas cut\u00e2neos de c\u00e9lulas B<\/strong>&nbsp;(por exemplo, linfoma prim\u00e1rio de grandes c\u00e9lulas B da pele)<\/li>\n\n\n\n<li><strong>Angioendoteliomatose reactiva<\/strong>&nbsp;(prolifera\u00e7\u00e3o benigna, n\u00e3o clonal)<\/li>\n\n\n\n<li><strong>Linfoma intravascular de c\u00e9lulas T<\/strong>&nbsp;(raro, morfologia semelhante, mas fen\u00f3tipo de c\u00e9lulas T)<\/li>\n\n\n\n<li><strong>Linfoma de efus\u00e3o prim\u00e1ria<\/strong><\/li>\n\n\n\n<li><strong>Sarcoma de Kaposi<\/strong><\/li>\n\n\n\n<li><strong>Vasculite<\/strong>&nbsp;(por exemplo, poliarterite nodosa)<\/li>\n\n\n\n<li><strong>Microangiopatias tromb\u00f3ticas<\/strong>&nbsp;(por exemplo, HUS\/TTP)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie_und_Prognose-6\"><\/span>Terapia e progn\u00f3stico<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Terapia padr\u00e3o<\/strong><br><strong>Protocolo R-CHOP<\/strong>&nbsp;(rituximab, ciclofosfamida, doxorrubicina, vincristina, prednisolona), frequentemente 6 ciclos<\/li>\n\n\n\n<li><strong>Terapias aditivas<\/strong><br>Com envolvimento do SNC:&nbsp;<strong>Profilaxia do SNC<\/strong>&nbsp;(por exemplo, metotrexato intratecal), possivelmente&nbsp;<strong>Terapia intensiva com rituximab<\/strong>&nbsp;ou&nbsp;<strong>Transplante aut\u00f3logo de c\u00e9lulas estaminais<\/strong>&nbsp;sobre a resposta<\/li>\n\n\n\n<li><strong>Previs\u00e3o<\/strong><br><strong>Desfavor\u00e1vel<\/strong>, especialmente no caso de infesta\u00e7\u00e3o do SNC ou de m\u00faltiplos \u00f3rg\u00e3os<br>O diagn\u00f3stico e o tratamento precoces melhoram a taxa de sobreviv\u00eancia<br>A taxa de sobreviv\u00eancia a 5 anos \u00e9 de cerca de 30-50 %, dependendo da gravidade da infe\u00e7\u00e3o e da resposta \u00e0 terap\u00eautica<\/li>\n<\/ul>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\"><strong>Perceber<\/strong>A doen\u00e7a \u00e9 extremamente rara e muitas vezes dif\u00edcil de diagnosticar. O diagn\u00f3stico diferencial deve ser efectuado cuidadosamente, uma vez que os achados cl\u00ednicos e radiol\u00f3gicos s\u00e3o inespec\u00edficos. A&nbsp;<strong>equipa multidisciplinar<\/strong>&nbsp;(dermatologia, hematologia, neurologia, patologia) \u00e9 crucial para um diagn\u00f3stico e uma terapia corretos.<\/p>\n<\/blockquote>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"PEL\"><span class=\"ez-toc-section\" id=\"Primar_Effusions-Lymphom_PEL\"><\/span><strong>Linfoma de efus\u00e3o prim\u00e1ria (PEL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Linfoma de efus\u00e3o prim\u00e1ria (PEL)<\/strong>&nbsp;\u00e9 um tipo raro e agressivo de linfoma de c\u00e9lulas B que se manifesta tipicamente como derrames linfomatosos nas cavidades corporais (pleura, peritoneu, peric\u00e1rdio) sem formar uma massa tumoral reconhec\u00edvel.<br>\u00c9&nbsp;<strong>invari\u00e1vel com o herpesv\u00edrus humano 8 (HHV-8, tamb\u00e9m KSHV)<\/strong>&nbsp;e ocorre quase exclusivamente em doentes imunocomprometidos, especialmente em pessoas seropositivas com SIDA avan\u00e7ada.<br>A doen\u00e7a apresenta uma&nbsp;<strong>Diferencia\u00e7\u00e3o plasmobl\u00e1stica<\/strong>&nbsp;com express\u00e3o de marcadores como CD38, CD138, MUM1\/IRF4 e LANA-1 (antig\u00e9nio nuclear associado \u00e0 lat\u00eancia-1), mas sem express\u00e3o de marcadores de c\u00e9lulas pan-B como CD19, CD20 e CD79a.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-12\"><\/span>Diagn\u00f3stico diferencial<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Linfoma difuso de grandes c\u00e9lulas B (DLBCL)<\/strong><br>Pode tamb\u00e9m estar associada a efus\u00f5es, mas difere pela aus\u00eancia de associa\u00e7\u00e3o com o HHV-8 e pela express\u00e3o de marcadores de c\u00e9lulas B<br>O DLBCL apresenta frequentemente rearranjos do gene c-myc que est\u00e3o ausentes no PEL<\/li>\n\n\n\n<li><strong>Linfoma de Burkitt<\/strong><br>Raramente pode ocorrer com efus\u00f5es, mas caracteriza-se por uma&nbsp;<strong>Rearranjo MYC<\/strong>&nbsp;caracterizado e apresenta tipicamente uma citomorfologia homog\u00e9nea de c\u00e9lulas pequenas<br>O rearranjo MYC \u00e9 comum em casos de PEL negativos para HHV-8 com morfologia tipo Burkitt<\/li>\n\n\n\n<li><strong>Linfoma anapl\u00e1sico de grandes c\u00e9lulas (ALCL)<\/strong><br>Pode estar associado a efus\u00f5es, mas caracteriza-se pela express\u00e3o de CD30 e ALK (em ALCL ALK-positivo)<br>O PEL \u00e9 tipicamente ALK-negativo e apresenta diferencia\u00e7\u00e3o plasmabl\u00e1stica<\/li>\n\n\n\n<li><strong>Linfoma associado ao piot\u00f3rax (BAL)<\/strong><br>Desenvolve-se em per\u00edodos pleurais cr\u00f3nicos, geralmente em doentes com inflama\u00e7\u00e3o pr\u00e9-existente<br>\u00c9&nbsp;<strong>n\u00e3o associado ao HHV-8<\/strong>, apresenta frequentemente um fen\u00f3tipo de c\u00e9lulas B e ocorre num contexto cl\u00ednico diferente<\/li>\n\n\n\n<li><strong>HHV-8-negativo, linfomas do tipo PEL (PEL de tipo II)<\/strong><br>Um subgrupo raro sem infe\u00e7\u00e3o por HHV-8 que ocorre em doentes mais velhos, imunocompetentes e com doen\u00e7as subjacentes (por exemplo, cirrose hep\u00e1tica, insufici\u00eancia renal, insufici\u00eancia card\u00edaca)<br>Estes casos mostram uma&nbsp;<strong>Fenotipagem de c\u00e9lulas B<\/strong>&nbsp;(CD19, CD20 positivo),&nbsp;<strong>Rearranjos MYC frequentes<\/strong>&nbsp;e um&nbsp;<strong>Melhor progn\u00f3stico<\/strong>&nbsp;como um PEL cl\u00e1ssico<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_und_immunophanotypische_Unterscheidung\"><\/span>Diferencia\u00e7\u00e3o cl\u00ednica e imunofenot\u00edpica<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><tbody><tr><td class=\"has-text-align-left\" data-align=\"left\">Carater\u00edstica<\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>PEL cl\u00e1ssico (Tipo I)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Linfomas tipo PEL negativos para HHV-8 (tipo II)<\/strong><\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>HHV-8<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Positivo<\/strong>&nbsp;(obrigat\u00f3rio)<\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Negativo<\/strong><\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Estado de VIH<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Maioritariamente positivo (SIDA avan\u00e7ada)<\/td><td class=\"has-text-align-left\" data-align=\"left\">Maioritariamente negativo, doentes mais velhos<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Imunossupress\u00e3o<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Muito pronunciado<\/td><td class=\"has-text-align-left\" data-align=\"left\">Raro, frequentemente devido a fraqueza relacionada com a idade (imunosenesc\u00eancia)<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Morfologia celular<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Plasmabl\u00e1stico, imunobl\u00e1stico<\/td><td class=\"has-text-align-left\" data-align=\"left\">Plasmabl\u00e1stica, imunobl\u00e1stica,&nbsp;<strong>tamb\u00e9m do tipo Burkitt<\/strong><\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Marcador de c\u00e9lulas B<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Negativo<\/strong>&nbsp;(CD19, CD20, CD79a)<\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Positivo<\/strong>&nbsp;(CD19, CD20, CD79a)<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Marcadores de c\u00e9lulas plasm\u00e1ticas<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Positivo<\/strong>&nbsp;(CD38, CD138, MUM1)<\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Negativo<\/strong><\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Rearranjo MYC<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Raro (3%)<\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Frequente (29%)<\/strong><\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Associa\u00e7\u00e3o do EBV<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Alta (65-80%)<\/td><td class=\"has-text-align-left\" data-align=\"left\">Baixo (13-30%)<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Previs\u00e3o<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Muito mau (sobreviv\u00eancia mediana &lt;6 meses)<\/td><td class=\"has-text-align-left\" data-align=\"left\">Melhor (taxa de sobreviv\u00eancia a 1 ano 47%)<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>Diagn\u00f3stico<\/strong>&nbsp;do PEL define o&nbsp;<strong>Detetabilidade do HHV-8 (atrav\u00e9s de imunohistoqu\u00edmica LANA-1)<\/strong>&nbsp;\u00e0 frente.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Se se suspeitar de linfomas de efus\u00e3o negativos para o HHV-8, \u00e9 crucial uma an\u00e1lise diferenciada da citomorfologia, imunofenotipagem, genotipagem (MYC, BCL2, BCL6) e antecedentes cl\u00ednicos.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u00c9 necess\u00e1ria uma abordagem multidisciplinar que combine citologia, citometria de fluxo, m\u00e9todos biol\u00f3gicos moleculares e imunohistoqu\u00edmicos para diferenciar corretamente a PEL e os seus diagn\u00f3sticos diferenciais.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"PEL\"><span class=\"ez-toc-section\" id=\"HHV8-Assoziiiertes_Lymphom\"><\/span><strong>Linfoma associado ao HHV8<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Linfoma associado ao HHV-8<\/strong>&nbsp;\u00e9 uma neoplasia rara causada pelo herpesv\u00edrus humano 8 (HHV-8), que ocorre principalmente em doentes infectados pelo VIH.  Pertence a um grupo de doen\u00e7as linfoproliferativas associadas ao HHV-8, incluindo a&nbsp;<strong>linfoma de efus\u00e3o prim\u00e1ria (PEL)<\/strong>que&nbsp;<strong>doen\u00e7a de Castleman multic\u00eantrica (MCD)<\/strong>&nbsp;e isso&nbsp;<strong>Linfoma plasmobl\u00e1stico associado \u00e0 MCD<\/strong>.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-13\"><\/span>Diagn\u00f3stico diferencial<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">A apresenta\u00e7\u00e3o diferencial do linfoma associado ao HHV-8 inclui as seguintes doen\u00e7as:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Linfoma de efus\u00e3o prim\u00e1ria (PEL)<\/strong><br>Caracterizada por cavidades cheias de l\u00edquido (derrames pleurais, peritoneais ou peric\u00e1rdicos) com c\u00e9lulas plasmabl\u00e1sticas positivas para HHV-8 e EBV<br>Ocorre geralmente em doentes seropositivos e n\u00e3o apresenta um envolvimento t\u00edpico dos g\u00e2nglios linf\u00e1ticos<\/li>\n\n\n\n<li><strong>Doen\u00e7a de Castleman multic\u00eantrica (DMC)<\/strong><br>Doen\u00e7a sist\u00e9mica com aumento de m\u00faltiplos g\u00e2nglios linf\u00e1ticos, acompanhada de febre, perda de peso, hepato- e esplenomegalia e citocinas elevadas, como a IL-6<br>Na DMC associada ao HHV-8, o v\u00edrus \u00e9 detet\u00e1vel nos plasm\u00f3citos e existe uma estreita associa\u00e7\u00e3o com a infe\u00e7\u00e3o pelo VIH<\/li>\n\n\n\n<li><strong>Linfoma plasmobl\u00e1stico associado \u00e0 MCD<\/strong><br>Um linfoma plasmabl\u00e1stico altamente maligno que ocorre frequentemente no f\u00edgado, no abd\u00f3men ou nos g\u00e2nglios linf\u00e1ticos<br>Apresenta positividade para o HHV-8 nas c\u00e9lulas tumorais e pode estar relacionado com um PEL&nbsp;<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_und_histologische_Merkmale\"><\/span>Carater\u00edsticas cl\u00ednicas e histol\u00f3gicas<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Citologia<\/strong><br>Plasmablastos com n\u00facleos grandes e irregulares, nucl\u00e9olos proeminentes e citoplasmas bas\u00f3filos<\/li>\n\n\n\n<li><strong>Imunohistoqu\u00edmica<\/strong><br>Positivo para CD45, CD79a, CD138, MUM1, cadeias \u03bb ou \u03ba, mas negativo para CD20 e CD30<\/li>\n\n\n\n<li><strong>Dete\u00e7\u00e3o de v\u00edrus<\/strong><br>HHV-8 por hibrida\u00e7\u00e3o in situ (EBER) e dete\u00e7\u00e3o da interleucina viral (vIL-6) em c\u00e9lulas tumorais<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_zu_anderen_Lymphomen\"><\/span>Diagn\u00f3stico diferencial com outros linfomas<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Linfoma n\u00e3o-Hodgkin (LNH)<\/strong><br>Especialmente linfomas plasmabl\u00e1sticos sem associa\u00e7\u00e3o com o HHV-8<\/li>\n\n\n\n<li><strong>Sarcoma de Kaposi<\/strong><br>Tamb\u00e9m associada ao HHV-8, mas histologicamente caracterizada por c\u00e9lulas fusiformes e prolifera\u00e7\u00e3o vascular<\/li>\n\n\n\n<li><strong>Linfadenopatias reactivas<\/strong><br>Em doen\u00e7as infecciosas ou auto-imunes, que tamb\u00e9m podem causar aumento dos g\u00e2nglios linf\u00e1ticos e liberta\u00e7\u00e3o de citocinas<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial requer uma combina\u00e7\u00e3o de achados cl\u00ednicos, an\u00e1lise histol\u00f3gica e dete\u00e7\u00e3o biol\u00f3gica molecular do HHV-8.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"T-Zell-_und_NK-Zell-Lymphome\"><\/span><strong>Linfomas de c\u00e9lulas T e de c\u00e9lulas NK<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"PTCL-NOS\"><span class=\"ez-toc-section\" id=\"Peripheres_T-Zell-Lymphom_PTCL-NOS\"><\/span><strong>Linfoma perif\u00e9rico de c\u00e9lulas T (PTCL-NOS)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Linfomas perif\u00e9ricos de c\u00e9lulas T (PTCL-NOS)<\/strong>&nbsp;s\u00e3o um grupo heterog\u00e9neo de linfomas de c\u00e9lulas T maduras raros, geralmente agressivos, que resultam do termo coletivo \u201ePTCL\u201c se n\u00e3o for poss\u00edvel uma subtipagem espec\u00edfica.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico de PTCL-NOS requer um&nbsp;<strong>diagn\u00f3stico multimodal<\/strong>&nbsp;(histologia, ICH, an\u00e1lise gen\u00e9tica). O diagn\u00f3stico diferencial \u00e9 complexo, especialmente em compara\u00e7\u00e3o com AITL e ALCL.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">O progn\u00f3stico \u00e9 mau, mas a sobreviv\u00eancia \u00e9 fortemente diferenciada de acordo com os subgrupos biol\u00f3gicos moleculares. Se poss\u00edvel, a terapia deve ser&nbsp;<strong>estudos cl\u00ednicos<\/strong>&nbsp;ter lugar.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisch-morphologische_Merkmale-6\"><\/span>Carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Sintomas cl\u00ednicos<\/strong><br>As manifesta\u00e7\u00f5es mais comuns s\u00e3o&nbsp;<strong>aumento indolor dos g\u00e2nglios linf\u00e1ticos<\/strong>,&nbsp;<strong>Sintomas B<\/strong>&nbsp;(febre, suores noturnos, perda de peso),&nbsp;<strong>Hepatoesplenomegalia<\/strong>&nbsp;e les\u00f5es extranodais (por exemplo, pele, trato gastrointestinal).<br>Um&nbsp;<strong>Hipergamaglobulinemia policlonal<\/strong>&nbsp;ou&nbsp;<strong>Anemia hemol\u00edtica positiva de Coombs<\/strong>&nbsp;pode ocorrer em cursos do tipo AITL.&nbsp;<\/li>\n\n\n\n<li><strong>Morfologia<\/strong><br>Histologicamente, o PTCL-NOS apresenta uma arquitetura vari\u00e1vel:<br>- <strong>Padr\u00e3o 1<\/strong>&nbsp;(infiltra\u00e7\u00e3o paracortical parcial em torno de centros germinais hiperpl\u00e1sicos)<br>- <strong>Padr\u00e3o 2<\/strong>&nbsp;(infiltra\u00e7\u00e3o paracortical extensa em torno de centros de germina\u00e7\u00e3o regressivos)<br>- <strong>Padr\u00e3o 3<\/strong>&nbsp;(arquitetura completamente anulada). Uma infiltra\u00e7\u00e3o rica em c\u00e9lulas epitelioides e histi\u00f3citos requer um diagn\u00f3stico diferencial com doen\u00e7as granulomatosas ou linfoma de Lennert.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-14\"><\/span>Diagn\u00f3stico diferencial<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>Diferencia\u00e7\u00e3o de outros linfomas<\/strong>&nbsp;\u00e9 fundamental:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Linfoma angioimunobl\u00e1stico de c\u00e9lulas T (AITL)<\/strong><br>O PTCL-NOS pode ser semelhante ao AITL. Diferencia\u00e7\u00e3o por&nbsp;<strong>marcadores imunohistoqu\u00edmicos<\/strong>&nbsp;(CD10, PD-1, BCL6, CXCL13) e&nbsp;<strong>An\u00e1lises de express\u00e3o g\u00e9nica<\/strong><br>Os AITL apresentam normalmente uma forte express\u00e3o de marcadores TFH e um rearranjo clonal do gene do recetor de c\u00e9lulas T<\/li>\n\n\n\n<li><strong>Linfoma anapl\u00e1sico de grandes c\u00e9lulas (ALCL) ALK-negativo<\/strong><br>Caracterizado por&nbsp;<strong>express\u00e3o forte e uniforme de CD30<\/strong>,&nbsp;<strong>imunofen\u00f3tipo citot\u00f3xico<\/strong>&nbsp;(CD8+, granzima B+, TIA-1+) e&nbsp;<strong>Rearranjo do gene do recetor de c\u00e9lulas T<\/strong><br>O&nbsp;<strong>t(2;5)(p23;q35)<\/strong>-A transloca\u00e7\u00e3o com o gene de fus\u00e3o NPM-ALK \u00e9 t\u00edpica do ALCL, mas n\u00e3o do PTCL-NOS<\/li>\n\n\n\n<li><strong>Altera\u00e7\u00f5es reactivas dos g\u00e2nglios linf\u00e1ticos<\/strong><br>A linfadenite de Kikuchi (necrose irregular, aus\u00eancia de clonalidade) ou a inflama\u00e7\u00e3o cr\u00f3nica podem simular PTCL-NOS<br><strong>Prova de clonalidade<\/strong>&nbsp;(PCR para o rearranjo do gene TCR) \u00e9 crucial<\/li>\n\n\n\n<li><strong>Linfomas nodais perif\u00e9ricos de c\u00e9lulas T com fen\u00f3tipo T-folicular auxiliar<\/strong><br>Uma entidade recentemente definida (OMS 2017) que costumava pertencer ao PTCL-NOS<br>Tem um&nbsp;<strong>CD4+\/BCL6+\/PD-1+<\/strong>-express\u00e3o e muta\u00e7\u00f5es em&nbsp;<strong>TET2, IDH2, DNMT3A<\/strong>&nbsp;sobre.<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methoden-9\"><\/span>M\u00e9todos de diagn\u00f3stico<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Imunohistoqu\u00edmica (ICH)<\/strong><br>- Os principais marcadores s\u00e3o&nbsp;<strong>CD3, CD4, CD5, CD2, CD7<\/strong>&nbsp;(frequentemente reduzido).<br>- <strong>Express\u00e3o de CD30<\/strong>&nbsp;\u00e9&nbsp;<strong>heterog\u00e9neo<\/strong>&nbsp;(CD30+ vs. CD30-), sendo que o grupo CD30+ apresenta melhor progn\u00f3stico e semelhan\u00e7a com o ALCL<\/li>\n\n\n\n<li><strong>An\u00e1lises de express\u00e3o g\u00e9nica<\/strong><br>Diferencia\u00e7\u00e3o em dois grupos principais:<br>- <strong>Grupo GATA3<\/strong>&nbsp;(baixa sobreviv\u00eancia aos 5 anos:&nbsp;<strong>19 %<\/strong>)<br>- <strong>Grupo TBX21<\/strong>&nbsp;(maior sobrevida em 5 anos:&nbsp;<strong>38 %<\/strong>)<\/li>\n\n\n\n<li><strong>Gen\u00e9tica molecular<\/strong><br>- <strong>Muta\u00e7\u00f5es nos reguladores epigen\u00e9ticos<\/strong>&nbsp;(TET2, DNMT3A, IDH2, MLL2, KDM6A) em cerca de 25 %<br>- <strong>t(5;9)(q33;q22)<\/strong>&nbsp;com gene de fus\u00e3o ITK\/SYK (aprox. 10 %)<br>- <strong>Produtos de fus\u00e3o VAV1<\/strong>&nbsp;(11 %)<\/li>\n\n\n\n<li><strong>Tecnologia de microarray<\/strong><br>Diferencia\u00e7\u00e3o de AITL, ALCL e PTCL-NOS com uma exatid\u00e3o de at\u00e9 98 %<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-10\"><\/span>Terapia<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Terapia prim\u00e1ria<\/strong><br>- <strong>Quimioterapia \u00e0 base de antraciclinas CHOP ou semelhante a CHOP<\/strong>&nbsp;\u00e9 normal.<br><strong>- Brentuximab vedotina<\/strong>&nbsp;(anti-CD30) \u00e9 utilizado em PTCL-NOS CD30+; tamb\u00e9m foi observada uma resposta em casos CD30-negativos<\/li>\n\n\n\n<li><strong>Consolida\u00e7\u00e3o<\/strong><br>Com boa resposta \u00e0 terap\u00eautica de indu\u00e7\u00e3o<br><strong>Transplante aut\u00f3logo de c\u00e9lulas estaminais (auto-SZT)<\/strong><\/li>\n\n\n\n<li><strong>Recorrente\/refrat\u00e1rio<\/strong><br><strong>Transplante alog\u00e9nico de c\u00e9lulas estaminais (allo-SZT)<\/strong>,&nbsp;<strong>Romidepsina<\/strong>,&nbsp;<strong>Belinostato<\/strong>,&nbsp;<strong>Pralatrexato<\/strong><\/li>\n\n\n\n<li><strong>Terapias direcionadas<\/strong><br>- Subst\u00e2ncias hipometilantes (por exemplo, azacitidina) para muta\u00e7\u00f5es TET2<br>- <strong>Inibidores JAK\/STAT<\/strong>&nbsp;para muta\u00e7\u00f5es activadoras de STAT3<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-9\"><\/span>Previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Sobreviv\u00eancia global mediana<\/strong><br><strong>10,5 meses<\/strong>&nbsp;para PTL-NOS-CD30-<br><strong>19-38 % Taxa de sobreviv\u00eancia a 5 anos<\/strong>&nbsp;dependendo da assinatura gen\u00e9tica (GATA3 vs. TBX21)<\/li>\n\n\n\n<li><strong>Factores de progn\u00f3stico<\/strong><br><strong>Express\u00e3o de CD30<\/strong>,&nbsp;<strong>Assinatura de genes (GATA3\/TBX21)<\/strong>,&nbsp;<strong>Grupo et\u00e1rio<\/strong>,&nbsp;<strong>Estadio da doen\u00e7a<\/strong>,&nbsp;<strong>Estado de recorr\u00eancia<\/strong><\/li>\n\n\n\n<li><strong>Pedido de terapia<\/strong><br>Principalmente curativo, mas&nbsp;<strong>Nenhum avan\u00e7o terap\u00eautico<\/strong>&nbsp;durante anos.<br><strong>Estudos cl\u00ednicos<\/strong>&nbsp;s\u00e3o recomendados.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"AITL\"><span class=\"ez-toc-section\" id=\"Angioimmunoblastisches_T-Zell-Lymphom_AITL\"><\/span><strong>Linfoma angioimunobl\u00e1stico de c\u00e9lulas T (AITL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O <strong>Linfoma angioimunobl\u00e1stico de c\u00e9lulas T (AITL)<\/strong>&nbsp;\u00e9 um linfoma perif\u00e9rico de c\u00e9lulas T raro e agressivo que se caracteriza por&nbsp;<strong>c\u00e9lulas T helper foliculares (TFH)<\/strong>&nbsp;e sobre&nbsp;<strong>1-2 % de todos os linfomas n\u00e3o-Hodgkin<\/strong>&nbsp;\u00e9 a principal causa.  Afecta predominantemente doentes idosos na 6\u00aa a 7\u00aa d\u00e9cada de vida e caracteriza-se por sintomas cl\u00ednicos complexos e frequentemente inespec\u00edficos.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\" id=\"klinische-merkmale-und-morphologische-zeichen\"><span class=\"ez-toc-section\" id=\"Klinische_Merkmale_und_morphologische_Zeichen\"><\/span><strong>Carater\u00edsticas cl\u00ednicas e sinais morfol\u00f3gicos<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Sintomas comuns<\/strong><br>- <strong>Sintomas B<\/strong>Febre, suores noturnos, perda de peso, fadiga<br>- <strong>Linfadenopatia generalizada<\/strong>&nbsp;(pesco\u00e7o, axila, virilha)<br>- <strong>Hepatoesplenomegalia<\/strong><br>- <strong>Anemia<\/strong>,&nbsp;<strong>Trombocitopenia<\/strong>,&nbsp;<strong>Linfopenia<\/strong><br>- <strong>Hipergamaglobulinemia policlonal<\/strong>&nbsp;e&nbsp;<strong>Hipereosinofilia<\/strong>&nbsp;(em 30-40 %)<br>- <strong>Edema<\/strong>&nbsp;(por exemplo, edema facial, ascite, edema pulmonar)<br>- <strong>Artralgias<\/strong>,&nbsp;<strong>Suscetibilidade \u00e0 infe\u00e7\u00e3o<\/strong>,&nbsp;<strong>doen\u00e7as neurol\u00f3gicas<\/strong>&nbsp;(por exemplo, polineuropatia)<\/li>\n\n\n\n<li><strong>Manifesta\u00e7\u00f5es cut\u00e2neas<\/strong>&nbsp;(para um m\u00e1ximo de 50 doentes %)<br>- <strong>Exantema maculopapular<\/strong>&nbsp;(frequentemente os primeiros sintomas)<br>- <strong>coceira<\/strong>&nbsp;(prurido)<br>- <strong>Padr\u00e3o de manchas e n\u00f3dulos<\/strong>&nbsp;com \u201esinal da cadeira de conv\u00e9s\u201c (omiss\u00e3o das pregas cut\u00e2neas)<br>- <strong>Les\u00f5es nodulares ou em forma de placa<\/strong>, que s\u00e3o&nbsp;<strong>Micose fung\u00f3ide<\/strong>&nbsp;ser capaz de se lembrar<br>- <strong>Raro<\/strong>Associa\u00e7\u00e3o com&nbsp;<strong>dermatose IgA linear<\/strong>&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\" id=\"differenzialdiagnose\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnose-2\"><\/span><strong>Diagn\u00f3stico diferencial<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O AITL \u00e9 muitas vezes erradamente designado por&nbsp;<strong>Doen\u00e7a infecciosa ou relacionada com drogas<\/strong>&nbsp;diagnosticada porque os sintomas se sobrep\u00f5em fortemente:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>S\u00edndrome DRESS (Rea\u00e7\u00e3o medicamentosa com eosinofilia e sintomas sist\u00e9micos)<\/strong><br>- Sintomas semelhantes: Febre, exantema, linfadenopatia, eosinofilia, hipergamaglobulinemia<br>- Diferencia\u00e7\u00e3o atrav\u00e9s de&nbsp;<strong>Historial m\u00e9dico (ingest\u00e3o de medicamentos)<\/strong>,&nbsp;<strong>dete\u00e7\u00e3o negativa do EBV no soro<\/strong>,&nbsp;<strong>Aus\u00eancia de prolifera\u00e7\u00e3o clonal de c\u00e9lulas T<\/strong><br>- <strong>AITL: EBV-positivo, altera\u00e7\u00e3o clonal do genoma das c\u00e9lulas T<\/strong><\/li>\n\n\n\n<li><strong>Doen\u00e7as infecciosas<\/strong><br>- <strong>V\u00edrus<\/strong> - EBV, VIH, VHC, HHV-6, hantav\u00edrus<br>- <strong>bact\u00e9rias<\/strong> -&nbsp;<em>Klebsiella pneumoniae<\/em>,&nbsp;<em>Mycoplasma<\/em>,&nbsp;<em>Borrelia<\/em><br>- <strong>Parasitas<\/strong> - Leishmania<br>- <strong>Diferencial - PCR, serologia, hemoculturas, an\u00e1lise do contexto cl\u00ednico<\/strong>&nbsp;<\/li>\n\n\n\n<li><strong>Outros linfomas<\/strong><br>- <strong>Linfomas perif\u00e9ricos de c\u00e9lulas T, NOS<\/strong>&nbsp;(n\u00e3o classificado de outra forma)<br>- <strong>Micose fung\u00f3ide<\/strong>&nbsp;(infiltra\u00e7\u00e3o cut\u00e2nea cont\u00ednua, fen\u00f3tipo CD4+\/CD8-)<br>- <strong>Linfoma de Hodgkin cl\u00e1ssico<\/strong>&nbsp;(c\u00e9lulas de Reed-Sternberg, CD15+\/CD30+)<br>- <strong>Linfoma de Lennert<\/strong>&nbsp;(infiltrados de c\u00e9lulas epitelioides, forte padr\u00e3o histiocit\u00e1rio)&nbsp;<\/li>\n\n\n\n<li><strong>Doen\u00e7as auto-imunes<\/strong><br>- <strong>S\u00edndrome de Still<\/strong>,&nbsp;<strong>LES<\/strong>,&nbsp;<strong>S\u00edndroma de Sj\u00f6gren<\/strong><br>- <strong>Diferencial - auto-anticorpos (ANA, ENA), crit\u00e9rios cl\u00ednicos<\/strong><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\" id=\"diagnostische-methodik\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methodik\"><\/span><strong>Metodologia de diagn\u00f3stico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ol start=\"1\" class=\"wp-block-list\">\n<li><strong>Exame cl\u00ednico<\/strong><br>- Palpa\u00e7\u00e3o dos g\u00e2nglios linf\u00e1ticos, f\u00edgado, ba\u00e7o<br>- Avalia\u00e7\u00e3o de les\u00f5es cut\u00e2neas, edema, enantema&nbsp;<\/li>\n\n\n\n<li><strong>Testes laboratoriais<\/strong><br>- <strong>Contagem sangu\u00ednea<\/strong> - Anemia, trombocitopenia, linfopenia, hipereosinofilia<br>- <strong>Par\u00e2metros de inflama\u00e7\u00e3o<\/strong> - CRP \u2191, BSG \u2191<br>- <strong>Testes de fun\u00e7\u00e3o<\/strong> - LDH \u2191, beta-2-microglobulina \u2191<br>- <strong>Eletroforese<\/strong> - Hipergamaglobulinemia<br>- <strong>PCR<\/strong> - ADN do EBV no soro (positivo em 80-90 casos de %)<\/li>\n\n\n\n<li><strong>Imagiologia<\/strong><br>- <strong>Sonografia\/CT\/RM<\/strong>Linfonodomegalia (multilocular), hepato-\/esplenomegalia, ascite<\/li>\n\n\n\n<li><strong>Bi\u00f3psia<\/strong><br>- <strong>Bi\u00f3psia de g\u00e2nglios linf\u00e1ticos<\/strong>&nbsp;(n\u00e3o sangue perif\u00e9rico ou biopsia da medula \u00f3ssea)<br>- <strong>Pato-histologia<\/strong><br>- Arquitetura abolida, infiltrado polim\u00f3rfico de linf\u00f3citos, histi\u00f3citos, eosin\u00f3filos, plasm\u00f3citos<br>\u2013 \u2013 <strong>V\u00e9nulas proliferadas e ramificadas<\/strong><br>\u2013 \u2013 <strong>Infiltrados perivasculares e paracorticais<\/strong><br>\u2013 \u2013 <strong>Imunoblastos B positivos para EBV<\/strong>&nbsp;(n\u00e3o nas c\u00e9lulas T)<br>\u2013 \u2013 <strong>C\u00e9lulas do tipo Reed-Sternberg<\/strong>&nbsp;poss\u00edvel<\/li>\n\n\n\n<li><strong>Imunohistoqu\u00edmica<\/strong><br>- <strong>Positivo<\/strong> - CD3, CD4, CD5, CD10, PD-1, ICOS, BCL6, CXCL13, CD20 (em c\u00e9lulas B)<br>- <strong>Negativo<\/strong>-CD8, CD30 (n\u00e3o em c\u00e9lulas Hodgkin t\u00edpicas)<br>- <strong>CXCL13 e CD10<\/strong> - Especificidade mais elevada para AITL&nbsp;<\/li>\n\n\n\n<li><strong>Citometria de fluxo<\/strong><br>- <strong>sCD3-\/CD4+<\/strong>&nbsp;C\u00e9lulas T no sangue perif\u00e9rico: valor preditivo positivo elevado&nbsp;<\/li>\n\n\n\n<li><strong>Biologia molecular<\/strong><br>- <strong>Rearranjo clonal do gene do recetor de c\u00e9lulas T<\/strong>&nbsp;(70-90 %)<br>- <strong>Muta\u00e7\u00f5es<\/strong>:&nbsp;<em>RHOA<\/em>&nbsp;(G17V),&nbsp;<em>TET2<\/em>,&nbsp;<em>IDH2<\/em>,&nbsp;<em>DNMT3A<\/em><br>- <strong>Fus\u00e3o do gene CTLA4\/CD28<\/strong>&nbsp;em 50 % dos casos&nbsp;<\/li>\n<\/ol>\n\n\n\n<h4 class=\"wp-block-heading\" id=\"therapie\"><span class=\"ez-toc-section\" id=\"Therapie-11\"><\/span><strong>Terapia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Primeira linha<\/strong><br>- <strong>Quimioterapia \u00e0 base de antraciclinas<\/strong><br>\u2013 \u2013 <strong>CHOP<\/strong>&nbsp;(ciclofosfamida, doxorrubicina, vincristina, prednisona)<br>\u2013 \u2013 <strong>R-CHOP<\/strong>&nbsp;(com rituximab)<br>\u2013 \u2013 <strong>CHOEP<\/strong>&nbsp;(com etoposido)<br>\u2013 \u2013 <strong>Adi\u00e7\u00e3o de Pegfilgrastim<\/strong>&nbsp;para profilaxia com granul\u00f3citos<\/li>\n\n\n\n<li><strong>Segunda linha - risco elevado \/ recorr\u00eancia<\/strong><br>- <strong>Transplante de c\u00e9lulas estaminais<\/strong>&nbsp;(aut\u00f3logo ou alog\u00e9nico) ap\u00f3s remiss\u00e3o<br>- <strong>Novos medicamentos em ensaios cl\u00ednicos<\/strong><br>\u2013 \u2013 <strong>Brentuximab vedotina<\/strong>&nbsp;(direcionado para CD30)<br>\u2013 \u2013 <strong>Brentuximab vedotina<\/strong>&nbsp;(direcionado para CD30)<br>\u2013 \u2013 <strong>Lenalidomida<\/strong>&nbsp;(imunomodulador)<\/li>\n\n\n\n<li><strong>Terapia paliativa em caso de resposta insuficiente<\/strong><br>- <strong>Glicocortic\u00f3ides<\/strong>&nbsp;(prednisona 80-100 mg\/dia, decrescente)<br>- <strong>Citost\u00e1ticos<\/strong>Clorambucil, ciclofosfamida<br>- <strong>Imunomoduladores<\/strong>Ciclosporina<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\" id=\"1-prognose-erg\u00e4nzung\"><span class=\"ez-toc-section\" id=\"Prognose-10\"><\/span><strong>Previs\u00e3o<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">A previs\u00e3o do&nbsp;<strong>Linfoma angioimunobl\u00e1stico de c\u00e9lulas T (AITL)<\/strong>&nbsp;\u00e9 global&nbsp;<strong>desfavor\u00e1vel<\/strong>, com um&nbsp;<strong>Taxa de sobreviv\u00eancia a 5 anos de cerca de 30-32 %<\/strong>&nbsp;e um&nbsp;<strong>tempo m\u00e9dio de sobreviv\u00eancia de 18-29 meses<\/strong>.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">S\u00e3o utilizadas v\u00e1rias classifica\u00e7\u00f5es de progn\u00f3stico para a estratifica\u00e7\u00e3o do risco:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>\u00cdndice Internacional de Progn\u00f3stico (IPI)<\/strong><br>Factores desfavor\u00e1veis:<br>- Idade &gt; 60 anos<br>- Estado de desempenho ECOG \u2265 2<br>- LDH elevada<br>- Est\u00e1dio de Ann Arbor \u2265 III<br>1 infesta\u00e7\u00e3o extranodal<\/li>\n\n\n\n<li><strong>\u00cdndice de Progn\u00f3stico para Linfoma de C\u00e9lulas T (PIT)<\/strong><br>Considerado:<br>- Idade &gt; 60 anos<br>- Estado de desempenho ECOG \u2265 2<br>- LDH elevada<br>- <strong>Infesta\u00e7\u00e3o da medula \u00f3ssea<\/strong><\/li>\n\n\n\n<li><strong>PIT modificado (mPIT)<\/strong><br>- Substitui a infesta\u00e7\u00e3o da medula \u00f3ssea por&nbsp;<strong>\u00cdndice de prolifera\u00e7\u00e3o Ki-67 &gt; 75 %<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Ao utilizar o&nbsp;<strong>Pontua\u00e7\u00f5es PIT<\/strong>&nbsp;as taxas de sobreviv\u00eancia a 5 anos para PTCL (incluindo AITL) s\u00e3o as seguintes<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Baixo risco<\/strong>: 75 %<\/li>\n\n\n\n<li><strong>Risco baixo-interm\u00e9dio<\/strong>: 30 %<\/li>\n\n\n\n<li><strong>Risco elevado-interm\u00e9dio<\/strong>: 15 %<\/li>\n\n\n\n<li><strong>Risco elevado<\/strong>: 0 %&nbsp;<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">UM&nbsp;<strong>Resultado altamente desfavor\u00e1vel<\/strong>&nbsp;\u00e9 utilizado para&nbsp;<strong>Fase IVB<\/strong>,&nbsp;<strong>Infiltra\u00e7\u00e3o da medula \u00f3ssea<\/strong>&nbsp;(como no estudo de caso com 10 %) e&nbsp;<strong>Aus\u00eancia de remiss\u00e3o ap\u00f3s a terapia inicial<\/strong>&nbsp;esperado.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"PTFCL\"><span class=\"ez-toc-section\" id=\"Follikulares_T-Zell-Lymphom_PTFCL\"><\/span><strong>Linfoma folicular de c\u00e9lulas T (PTFCL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O <strong>Linfoma folicular de c\u00e9lulas T (FTCL)<\/strong>&nbsp;\u00e9 a mesma entidade e \u00e9 tamb\u00e9m utilizada sob estes sin\u00f3nimos <strong>PTFCL<\/strong>, <strong>F-PTCL<\/strong>, <strong>nTFHL<\/strong> um tipo muito raro e agressivo de linfoma de c\u00e9lulas T que pode ser diferenciado de&nbsp;<strong>c\u00e9lulas T helper foliculares (TFH)<\/strong>&nbsp;e consta como uma entidade independente na atual classifica\u00e7\u00e3o da OMS (2017). Anteriormente atribu\u00eddo ao grupo PTCL-NOS.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">O linfoma folicular de c\u00e9lulas T \u00e9 um tumor com&nbsp;<strong>fen\u00f3tipo carater\u00edstico do TFH<\/strong>, que se caracteriza por&nbsp;<strong>Diagn\u00f3stico diferencial de AITL, linfoma de Hodgkin e linfoma folicular de c\u00e9lulas B<\/strong>&nbsp;devem ser delimitados.<br>O diagn\u00f3stico requer&nbsp;<strong>Avalia\u00e7\u00e3o histol\u00f3gica e imunohistoqu\u00edmica cuidadosa<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A terapia \u00e9&nbsp;<strong>sintom\u00e1tico e emp\u00edrico<\/strong>, Previs\u00e3o&nbsp;<strong>desfavor\u00e1vel<\/strong>.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisch-morphologische_Merkmale-7\"><\/span>Carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Idade e g\u00e9nero<\/strong><br>Os afectados s\u00e3o principalmente&nbsp;<strong>Pessoas de idade m\u00e9dia a avan\u00e7ada (33-88 anos)<\/strong>, com um&nbsp;<strong>ligeira prefer\u00eancia por homens<\/strong><\/li>\n\n\n\n<li><strong>Apresenta\u00e7\u00e3o cl\u00ednica<\/strong><br>Semelhante ao&nbsp;<strong>linfoma angioimunobl\u00e1stico de c\u00e9lulas T (AITL)<\/strong><br>Os sintomas mais comuns s\u00e3o&nbsp;<strong>Linfadenopatia generalizada, esplenomegalia, sintomas B (febre, suores noturnos, perda de peso)<\/strong>&nbsp;e&nbsp;<strong>Les\u00f5es cut\u00e2neas em cerca de um ter\u00e7o dos doentes<\/strong><br>Estes s\u00e3o&nbsp;<strong>n\u00e3o \u00e9 t\u00edpico do MF<\/strong>&nbsp;(sem p\u00e1pulas\/placas escamosas e firmes)<\/li>\n\n\n\n<li><strong>Histologia<\/strong><br>Os g\u00e2nglios linf\u00e1ticos apresentam uma&nbsp;<strong>prolifera\u00e7\u00e3o nodular\/folicular de c\u00e9lulas linf\u00f3ides monom\u00f3rficas de tamanho m\u00e9dio<\/strong>&nbsp;com&nbsp;<strong>Infiltra\u00e7\u00e3o parcial ou total dos fol\u00edculos linf\u00e1ticos<\/strong><br>O&nbsp;<strong>A zona da bainha est\u00e1 reduzida ou ausente<\/strong><br>Em contraste com as altera\u00e7\u00f5es reactivas e os linfomas de c\u00e9lulas B (por exemplo, linfoma folicular), o&nbsp;<strong>Diferencia\u00e7\u00e3o dif\u00edcil sem imunohistoqu\u00edmica<\/strong><\/li>\n\n\n\n<li><strong>Imunofen\u00f3tipo<\/strong><br>As c\u00e9lulas neopl\u00e1sicas expressam&nbsp;<strong>Antig\u00e9nios de c\u00e9lulas Pan-T (CD2, CD3, CD5)<\/strong>, s\u00e3o&nbsp;<strong>CD4+<\/strong>,&nbsp;<strong>CD8-<\/strong>, mostrar&nbsp;<strong>Defici\u00eancia de CD7<\/strong>&nbsp;e um&nbsp;<strong>fen\u00f3tipo carater\u00edstico do TFH<\/strong>&nbsp;com express\u00e3o de&nbsp;<strong>PD-1, CXCL13, BCL6, CD10 e ICOS<\/strong><br><strong>Imunoblastos CD20-positivos<\/strong>&nbsp;s\u00e3o frequentemente&nbsp;<strong>EBV-positivo<\/strong>&nbsp;e pode mesmo&nbsp;<strong>C\u00e9lulas tipo Hodgkin\/Reed-Sternberg<\/strong>&nbsp;forma<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_-methodik\"><\/span>Diagn\u00f3stico diferencial e metodologia<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Diagn\u00f3sticos diferenciais mais importantes<\/strong><br>- <strong>Linfoma angioimunobl\u00e1stico de c\u00e9lulas T (AITL)<\/strong><br>Sintomas cl\u00ednicos e fen\u00f3tipo de TFH semelhantes, mas o FTCL n\u00e3o apresenta carater\u00edsticas t\u00edpicas de AITL, tais como&nbsp;<strong>prolifera\u00e7\u00e3o vascular, c\u00e9lulas FD e fundo inflamat\u00f3rio<\/strong><br>- <strong>Linfoma de Hodgkin (cl\u00e1ssico)<\/strong><br>As c\u00e9lulas CD30+\/CD15+ positivas para EBV podem apresentar o fen\u00f3tipo de c\u00e9lulas de Hodgkin. A diferencia\u00e7\u00e3o atrav\u00e9s de&nbsp;<strong>Imunofen\u00f3tipo e morfologia celular<\/strong><br>- <strong>Linfoma folicular (FL)<\/strong><br>Quadro morfol\u00f3gico semelhante (crescimento folicular), mas a FL \u00e9 uma&nbsp;<strong>Linfoma de c\u00e9lulas B<\/strong>&nbsp;com&nbsp;<strong>CD20+, CD5-, BCL6+ e BCL2+<\/strong>&nbsp;C\u00e9lulas<br><strong>O fen\u00f3tipo CD4+ TFH \u00e9 crucial para o FTCL<\/strong><br>- <strong>Linfoma da zona marginal ou linfoma de Hodgkin com predomin\u00e2ncia de linf\u00f3citos nodulares<\/strong><br>Diferencia\u00e7\u00e3o atrav\u00e9s de&nbsp;<strong>An\u00e1lises de imunofen\u00f3tipo e de biologia molecular<\/strong><\/li>\n\n\n\n<li><strong>Diagn\u00f3stico<\/strong><br>- <strong>Bi\u00f3psia de g\u00e2nglios linf\u00e1ticos<\/strong>&nbsp;com&nbsp;<strong>avalia\u00e7\u00e3o histol\u00f3gica e imunohistoqu\u00edmica distinta<\/strong>&nbsp;por um patologista experiente<br>- <strong>Imunohistoqu\u00edmica<\/strong> - Prova de&nbsp;<strong>CD4, PD-1, CXCL13, BCL6, CD10, ICOS<\/strong>&nbsp;e&nbsp;<strong>Aus\u00eancia de CD7<\/strong><br>- <strong>Biologia molecular<\/strong> -&nbsp;<strong>transloca\u00e7\u00e3o t(5;9)(q33;q22)<\/strong>&nbsp;(gene de fus\u00e3o ITK-SYK) em cerca de&nbsp;<strong>20 % de casos<\/strong>.<br>Muta\u00e7\u00f5es em&nbsp;<strong>RHOA, TET2, IDH2, DNMT3A<\/strong>&nbsp;tamb\u00e9m s\u00e3o descritos<br>- <strong>An\u00e1lise de clonalidade<\/strong> - Dete\u00e7\u00e3o de um genoma clonal do recetor de c\u00e9lulas T<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-12\"><\/span>Terapia<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Nenhuma terapia padr\u00e3o estabelecida<\/strong>&nbsp;devido ao n\u00famero reduzido de casos<\/li>\n\n\n\n<li><strong>Terapia de primeira linha<\/strong><br><strong>CHOP (ciclofosfamida, doxorrubicina, vincristina, prednisona)<\/strong><br>ou&nbsp;<strong>CHEOP<\/strong><\/li>\n\n\n\n<li><strong>Terapia de segunda linha<\/strong><br>Para pacientes adequados&nbsp;<strong>Transplante aut\u00f3logo ou alog\u00e9nico de c\u00e9lulas estaminais<\/strong>.&nbsp;<\/li>\n\n\n\n<li><strong>Estudos cl\u00ednicos<\/strong><br>Ensaio de novas terap\u00eauticas (por exemplo.&nbsp;<strong>Abordagens imunoterap\u00eauticas<\/strong>,&nbsp;<strong>Terapias direcionadas<\/strong>).&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-11\"><\/span>Previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Evolu\u00e7\u00e3o cl\u00ednica agressiva<\/strong>&nbsp;com&nbsp;<strong>Mau progn\u00f3stico<\/strong>.&nbsp;<\/li>\n\n\n\n<li><strong>Cerca de 50 % dos doentes morrem nos primeiros 24 meses ap\u00f3s o diagn\u00f3stico<\/strong>.&nbsp;<\/li>\n\n\n\n<li>O&nbsp;<strong>A taxa de sobreviv\u00eancia \u00e9 significativamente pior<\/strong>&nbsp;do que na maioria dos outros subtipos de PTCL.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"HTZL\"><span class=\"ez-toc-section\" id=\"Hepatosplenisches_T-Zell-Lymphom_%CE%B3%CE%B4-Typ\"><\/span>Linfoma hepatoespl\u00e9nico de c\u00e9lulas T (tipo \u03b3\u03b4)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O linfoma hepatoespl\u00e9nico de c\u00e9lulas T (HSTCL) \u00e9 um tipo de&nbsp;<strong>T-NHL sist\u00e9mico, muito raro, clinicamente agressivo<\/strong>&nbsp;(&lt;1% dos linfomas n\u00e3o Hodgkin), que se caracteriza principalmente por&nbsp;<strong>C\u00e9lulas \u03b3\u03b4-T<\/strong>&nbsp;descende de.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Caracteriza-se por uma&nbsp;<strong>Envolvimento exclusivo do ba\u00e7o, f\u00edgado e medula \u00f3ssea<\/strong>&nbsp;em que&nbsp;<strong>Linfadenopatia ou exsuda\u00e7\u00e3o leuc\u00e9mica geralmente ausentes<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A doen\u00e7a ocorre predominantemente na&nbsp;<strong>Da adolesc\u00eancia \u00e0 idade adulta jovem<\/strong>&nbsp;(idade m\u00e9dia: 38 anos), os homens s\u00e3o afectados com muito mais frequ\u00eancia. Uma percentagem significativa dos casos \u00e9&nbsp;<strong>imunossupress\u00e3o cr\u00f3nica<\/strong>&nbsp;associado.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_und_klinisch-morphologische_Merkmale\"><\/span><strong>Carater\u00edsticas cl\u00ednicas e cl\u00ednico-morfol\u00f3gicas<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Os doentes apresentam normalmente&nbsp;<strong>Sintomas B (febre, suores noturnos, perda de peso), hepatoesplenomegalia e pancitopenia<\/strong>, que pode ser uma reminisc\u00eancia de leucemia aguda.<br>UM&nbsp;<strong>s\u00edndrome hematofagoc\u00edtica<\/strong>&nbsp;tamb\u00e9m ocorre.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Laborat\u00f3rio<\/strong><br>- <strong>aumento da desidrogenase l\u00e1ctica (71,4 %<\/strong><br>- <strong>Disfun\u00e7\u00e3o hep\u00e1tica (42,9 %<\/strong><br>- <strong>Fibrinog\u00e9nio reduzido (35,7 %)<\/strong><\/li>\n\n\n\n<li><strong>Histologia<\/strong><br>Morfologicamente, o linfoma apresenta uma&nbsp;<strong>infiltrado sinusoidal, monom\u00f3rfico, de c\u00e9lulas de tamanho m\u00e9dio com citoplasma p\u00e1lido<\/strong>.<\/li>\n\n\n\n<li><strong>Imunofen\u00f3tipo<\/strong><br>O imunofen\u00f3tipo \u00e9 carater\u00edstico:&nbsp;<strong>CD3+, CD5-, CD8-, CD4-, CD56+, TCR \u03b3\u03b4+, Granzima B+<\/strong>, principalmente&nbsp;<strong>TCR \u03b1\u03b2 negativo<\/strong><\/li>\n\n\n\n<li><strong>Biologia molecular<\/strong><br>Geneticamente s\u00e3o&nbsp;<strong>Isocromossoma 7q e trissomia 8<\/strong>&nbsp;as aberra\u00e7\u00f5es cromoss\u00f3micas mais comuns<br>Muta\u00e7\u00f5es em&nbsp;<strong>STAT3\/STAT5B (via de sinaliza\u00e7\u00e3o JAK-STAT)<\/strong>&nbsp;e&nbsp;<strong>SETD2, IN080, ARID1 (modifica\u00e7\u00e3o da cromatina)<\/strong>&nbsp;s\u00e3o frequentes e possivelmente relevantes do ponto de vista terap\u00eautico&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_-methodik-2\"><\/span><strong>Diagn\u00f3stico diferencial e metodologia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial inclui<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Leucemia aguda<\/strong>&nbsp;(especialmente com pancitopenia e leucocitose no sangue perif\u00e9rico)&nbsp;<\/li>\n\n\n\n<li><strong>Outros linfomas de c\u00e9lulas T<\/strong>&nbsp;(por exemplo.&nbsp;<strong>Leucemia prolinfoc\u00edtica de c\u00e9lulas T (T-PLL)<\/strong>,&nbsp;<strong>Linfoma angioimunobl\u00e1stico de c\u00e9lulas T (AITL)<\/strong>,&nbsp;<strong>Linfomas de c\u00e9lulas NK-\/T (ENKTL)<\/strong>)<\/li>\n\n\n\n<li><strong>S\u00edndrome hemofagoc\u00edtica (HLH)<\/strong> pode ser desencadeada por causas infecciosas, auto-imunol\u00f3gicas ou malignas<\/li>\n\n\n\n<li><strong>Outros linfomas extranodais<\/strong>&nbsp;com envolvimento do f\u00edgado\/ba\u00e7o<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Para um diagn\u00f3stico fi\u00e1vel&nbsp;<strong>obrigat\u00f3rio<\/strong>&nbsp;S\u00e3o necess\u00e1rios os seguintes m\u00e9todos:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Citomorfologia<\/strong>&nbsp;(sangue perif\u00e9rico, medula \u00f3ssea, biopsia do ba\u00e7o)<\/li>\n\n\n\n<li><strong>Imunofenotipagem<\/strong>&nbsp;(citometria de fluxo) com dete\u00e7\u00e3o do fen\u00f3tipo das c\u00e9lulas T \u03b3\u03b4<\/li>\n\n\n\n<li><strong>An\u00e1lise cromoss\u00f3mica<\/strong>&nbsp;e&nbsp;<strong>PEIXE<\/strong>&nbsp;para a dete\u00e7\u00e3o de 7q e trissomia 8<\/li>\n\n\n\n<li><strong>Gen\u00e9tica molecular<\/strong>&nbsp;(PCR para rearranjos do gene TCR, sequencia\u00e7\u00e3o para dete\u00e7\u00e3o de muta\u00e7\u00f5es em STAT3, SETD2, etc.)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-13\"><\/span><strong>Terapia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Existem&nbsp;<strong>n\u00e3o existe uma norma de tratamento uniforme<\/strong>. Atualmente, o&nbsp;<strong>Transplante alog\u00e9nico de c\u00e9lulas estaminais hematopoi\u00e9ticas (HSCT)<\/strong> a \u00fanica abordagem com efic\u00e1cia cl\u00ednica comprovada e \u00e9 utilizada em&nbsp;<strong>terapia de primeira linha pacientes com remiss\u00e3o<\/strong>&nbsp;recomendado para consolida\u00e7\u00e3o.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Quimioterapias (por ex.&nbsp;<strong>CHOP, EPOCH<\/strong>) t\u00eam um sucesso limitado e as recidivas s\u00e3o frequentes.&nbsp;&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-12\"><\/span>Previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>O progn\u00f3stico \u00e9 mau<\/strong><br>- O tempo m\u00e9dio de sobreviv\u00eancia \u00e9 inferior a tr\u00eas anos<br>- a taxa de sobreviv\u00eancia a 5 anos \u00e9 inferior a 20 %<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>A doen\u00e7a est\u00e1 associada a um elevado risco de recorr\u00eancia<\/strong>&nbsp;e&nbsp;<strong>baixa resposta \u00e0 terapia<\/strong>&nbsp;ligado.&nbsp;<\/p>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\"><strong>Perceber<\/strong>O diagn\u00f3stico exige um esclarecimento interdisciplinar por parte de oncologistas, hematologistas e patologistas. A situa\u00e7\u00e3o atual em termos de dados \u00e9 limitada, uma vez que a HSTCL \u00e9 uma doen\u00e7a muito rara.<\/p>\n<\/blockquote>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"EATZL\"><span class=\"ez-toc-section\" id=\"Enteropathie-assoziiertes_T-Zell-Lymphom_EATL\"><\/span><strong>Linfoma de c\u00e9lulas T associado a enteropatia (EATL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>Linfoma de c\u00e9lulas T associado a enteropatia (EATL)<\/strong>&nbsp;\u00e9 um linfoma n\u00e3o-Hodgkin agressivo do trato gastrointestinal que se desenvolve a partir de c\u00e9lulas T citot\u00f3xicas intraepiteliais intestinais.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A classifica\u00e7\u00e3o atual da OMS (2017) utiliza o termo&nbsp;<strong>EATL<\/strong>&nbsp;exclusivamente para o&nbsp;<strong>EATL tipo 1<\/strong>, que est\u00e1 associada a uma enteropatia sens\u00edvel ao gl\u00faten (doen\u00e7a cel\u00edaca).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>Tipo \u03b3\u03b4<\/strong>&nbsp;\u00e9 um subtipo raro, mas clinicamente relevante, que se caracteriza por um fen\u00f3tipo de c\u00e9lulas T \u03b3\u03b4 e requer uma aten\u00e7\u00e3o especial no diagn\u00f3stico diferencial.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild\"><\/span>Imagem cl\u00ednica<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Infesta\u00e7\u00e3o mais frequente<\/strong>Intestino delgado (especialmente jejuno), mesent\u00e9rio; localiza\u00e7\u00f5es mais raras no trato gastrointestinal.&nbsp;<\/li>\n\n\n\n<li><strong>Sintomas cl\u00ednicos<\/strong>Dor abdominal (sintoma mais comum), esteatorreia, perda de peso, m\u00e1 absor\u00e7\u00e3o, hemorragia gastrointestinal, anemia, sintomas B, obstru\u00e7\u00e3o ou perfura\u00e7\u00e3o intestinal.<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Morphologische_Merkmale\"><\/span><strong>Carater\u00edsticas morfol\u00f3gicas<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>EATL tipo 1 (cl\u00e1ssico)<\/strong>Associado \u00e0 doen\u00e7a cel\u00edaca;&nbsp;<strong>CD56-negativo<\/strong>,&nbsp;<strong>CD8+<\/strong>,&nbsp;<strong>CD56-negativo<\/strong>; Prolifera\u00e7\u00e3o clonal de c\u00e9lulas T com morfologia citot\u00f3xica<\/li>\n\n\n\n<li><strong>EATL tipo 2 (nova nomenclatura: linfoma epiteliotr\u00f3pico monom\u00f3rfico de c\u00e9lulas T intestinais, MEITL)<\/strong>:&nbsp;<strong>CD56-positivo<\/strong>,&nbsp;<strong>Nenhuma associa\u00e7\u00e3o com a doen\u00e7a cel\u00edaca<\/strong>, mais comum em pacientes mais velhos, curso agressivo<\/li>\n\n\n\n<li><strong>Subtipo de c\u00e9lulas T \u03b3\u03b4<\/strong>Raro, caracterizado por&nbsp;<strong>Express\u00e3o do recetor de c\u00e9lulas T \u03b3\u03b4<\/strong>,&nbsp;<strong>CD3+<\/strong>,&nbsp;<strong>CD56+<\/strong>,&nbsp;<strong>CD4-<\/strong>,&nbsp;<strong>CD8-<\/strong>; frequentemente com epiteliotropismo pronunciado e morfologia distinta.  A diferencia\u00e7\u00e3o de&nbsp;<strong>linfoprolifera\u00e7\u00f5es indolentes de c\u00e9lulas T<\/strong>&nbsp;(por exemplo, doen\u00e7a linfoproliferativa indolente das c\u00e9lulas T do trato gastrointestinal) \u00e9 crucial, uma vez que pode causar uma&nbsp;<strong>Doen\u00e7a benigna, de progress\u00e3o lenta<\/strong>&nbsp;com&nbsp;<strong>baixa taxa de prolifera\u00e7\u00e3o (10-15%)<\/strong>&nbsp;e&nbsp;<strong>infiltrado superficial<\/strong>&nbsp;representar.<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-15\"><\/span>Diagn\u00f3stico diferencial<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Doen\u00e7a cel\u00edaca refract\u00e1ria (DCR) tipo II<\/strong>Linf\u00f3citos T intra-epiteliais clonais com fen\u00f3tipo aberrante (por exemplo, CD8-, CD56+, TCR\u03b3\u03b4+), elevada taxa de transforma\u00e7\u00e3o em EATL<\/li>\n\n\n\n<li><strong>Linfoprolifera\u00e7\u00f5es indolentes de c\u00e9lulas T do trato gastrointestinal<\/strong>Infiltrado superficial, n\u00e3o destrutivo, baixa taxa de prolifera\u00e7\u00e3o,&nbsp;<strong>Sem processo tumoral maci\u00e7o<\/strong>,&nbsp;<strong>Citologia de manchas<\/strong>,&nbsp;<strong>Les\u00f5es persistentes sem progress\u00e3o<\/strong><\/li>\n\n\n\n<li><strong>Enteropatia\/gastropatia indolente por c\u00e9lulas NK<\/strong>CD3+, CD56+, CD4-, CD8-, c\u00e9lulas at\u00edpicas de tamanho m\u00e9dio,&nbsp;<strong>nenhum arranjo de genes de c\u00e9lulas T<\/strong><\/li>\n\n\n\n<li><strong>Linfomas extranodais de c\u00e9lulas NK\/T<\/strong>Associado ao v\u00edrus Epstein-Barr (EBV),&nbsp;<strong>n\u00e3o cel\u00edacos<\/strong>,&nbsp;<strong>CD56+<\/strong>,&nbsp;<strong>TIA1+<\/strong>,&nbsp;<strong>granzima B+<\/strong>,&nbsp;<strong>EBV-LMP1+<\/strong><\/li>\n\n\n\n<li><strong>Linfomas gastrointestinais de outras origens<\/strong>Linfomas de c\u00e9lulas B (por exemplo, linfoma difuso de grandes c\u00e9lulas B), linfoma folicular, linfoma da zona marginal<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methodik-2\"><\/span><strong>Metodologia de diagn\u00f3stico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Endoscopia com biopsia do intestino delgado<\/strong><br>Macrosc\u00f3pico: \u00falceras m\u00faltiplas, possibilidade de perfura\u00e7\u00f5es<\/li>\n\n\n\n<li><strong>Histologia<\/strong><br>Prova de&nbsp;<strong>Clonalidade das c\u00e9lulas T<\/strong>&nbsp;(PCR para rearranjos do gene TCR),&nbsp;<br><strong>perfis imunohistoqu\u00edmicos<\/strong>&nbsp;(CD3, CD4, CD8, CD56, TCR\u03b1\u03b2\/\u03b3\u03b4, CD57, granzima B)<\/li>\n\n\n\n<li><strong>Biologia molecular<\/strong><br>Prova&nbsp;<strong>muta\u00e7\u00f5es recorrentes na via de sinaliza\u00e7\u00e3o JAK\/STAT<\/strong>&nbsp;(por exemplo, STAT3, JAK1),<br><strong>ganhos cromoss\u00f3micos (9q33-q34)<\/strong>.<\/li>\n\n\n\n<li><strong>Rearranjos de DUSP22<\/strong><br>Raro na EATL, pode ocorrer em linfoprolifera\u00e7\u00f5es cut\u00e2neas CD30+, alargando o diagn\u00f3stico diferencial.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-14\"><\/span>Terapia<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Dieta consistente sem gl\u00faten<\/strong><br><strong>Profilaxia<\/strong>, pode impedir o desenvolvimento.&nbsp;<\/li>\n\n\n\n<li><strong>Quimioterapia<\/strong><br><strong>Regime CHOP<\/strong>&nbsp;(ciclofosfamida, doxorrubicina, vincristina, prednisona), se necess\u00e1rio com&nbsp;<strong>Etoposido<\/strong>&nbsp;para pacientes com menos de 60 anos de idade<\/li>\n\n\n\n<li><strong>Transplante aut\u00f3logo de c\u00e9lulas estaminais<\/strong><br>Op\u00e7\u00e3o para doentes mais jovens com doen\u00e7a recidivante ou refract\u00e1ria<\/li>\n\n\n\n<li><strong>Corticosteroides<\/strong><br>Para sintomas refract\u00e1rios de doen\u00e7a cel\u00edaca<\/li>\n\n\n\n<li><strong>Estrat\u00e9gia de observa\u00e7\u00e3o (Watch &amp; Wait)<\/strong><br>Apenas para linfoprolifera\u00e7\u00f5es indolentes, n\u00e3o para EATL.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-13\"><\/span>Previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Curso agressivo<\/strong>, elevada frequ\u00eancia de met\u00e1stases (f\u00edgado, ba\u00e7o, pele)<\/li>\n\n\n\n<li><strong>Perfura\u00e7\u00e3o intestinal<\/strong>&nbsp;como uma complica\u00e7\u00e3o t\u00edpica<\/li>\n\n\n\n<li><strong>Tempo m\u00e9dio de sobreviv\u00eancia desde o diagn\u00f3stico<\/strong>&nbsp;<strong>10 meses<\/strong><\/li>\n\n\n\n<li><strong>Factores de progn\u00f3stico<\/strong><br>Idade, est\u00e1dio, prolifera\u00e7\u00e3o clonal de c\u00e9lulas T, muta\u00e7\u00f5es na via JAK\/STAT, estado CD56, resposta \u00e0 terap\u00eautica.&nbsp;<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Resumo<\/strong>O diagn\u00f3stico diferencial da&nbsp;<strong>EATL de c\u00e9lulas T \u03b3\u03b4<\/strong>&nbsp;requer uma combina\u00e7\u00e3o estreita de an\u00e1lises cl\u00ednicas, endosc\u00f3picas, histol\u00f3gicas e de biologia molecular.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>Diagn\u00f3stico de exclus\u00e3o de linfoprolifera\u00e7\u00f5es indolentes<\/strong>&nbsp;\u00e9 crucial para evitar uma quimioterapia excessiva e prejudicial.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A terapia \u00e9 agressiva, o progn\u00f3stico \u00e9 mau, o diagn\u00f3stico e o tratamento precoces s\u00e3o vitais.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Anaplastisches_groszelliges_Lymphom_ALCL\"><\/span><strong>Linfoma anapl\u00e1sico de grandes c\u00e9lulas (ALCL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O <strong>Linfoma anapl\u00e1sico de grandes c\u00e9lulas (ALCL)<\/strong>&nbsp;\u00e9 raro e agressivo,&nbsp;<strong>Linfoma n\u00e3o-Hodgkin CD30-positivo<\/strong>, que se origina principalmente das c\u00e9lulas T e se encontra em grandes quantidades no&nbsp;<strong>Inf\u00e2ncia e in\u00edcio da idade adulta<\/strong>&nbsp;ocorre.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Divide-se em dois grupos principais:&nbsp;<strong>ALK-positivo (ALK+ ALCL)<\/strong>&nbsp;e&nbsp;<strong>ALK-negativo (ALK- ALCL)<\/strong>, A express\u00e3o de ALK causa diferen\u00e7as cl\u00ednicas, patol\u00f3gicas e de progn\u00f3stico decisivas.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild-2\"><\/span>Imagem cl\u00ednica<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>ALCL sist\u00e9mico<\/strong><br>Normalmente transporta&nbsp;<strong>Sintomas B<\/strong>&nbsp;(febre, suores noturnos, perda de peso), geralmente em fases avan\u00e7adas (III\/IV)<br>Infiltrados extranodais frequentes afectam a pele, o f\u00edgado, os pulm\u00f5es, os tecidos moles, os ossos e a medula \u00f3ssea (aprox. 15 %)<\/li>\n\n\n\n<li><strong>ALCL cut\u00e2neo prim\u00e1rio (cALCL)<\/strong><br>Ocorre principalmente em homens mais velhos, apresenta-se como&nbsp;<strong>Tumores cut\u00e2neos solit\u00e1rios e ulcerados<\/strong>&nbsp;com&nbsp;<strong>Previs\u00e3o favor\u00e1vel<\/strong>&nbsp;(taxa de sobreviv\u00eancia a 10 anos &gt;90 %)<br>Em contraste com o ALCL sist\u00e9mico, o cALCL&nbsp;<strong>ALK-negativo<\/strong>&nbsp;e&nbsp;<strong>EMA-negativo<\/strong><\/li>\n\n\n\n<li><strong>ALCL associado a implantes mam\u00e1rios (BIA-ALCL)<\/strong><br>Uma forma rara mas documentada, que pode ser&nbsp;<strong>ap\u00f3s anos ou d\u00e9cadas ap\u00f3s o implante<\/strong>&nbsp;manifestada na cavidade serosa (por exemplo, \u00e0 volta de implantes mam\u00e1rios)<br>Clinicamente como&nbsp;<strong>Exsudados serosos<\/strong>&nbsp;com infiltra\u00e7\u00e3o linfoc\u00edtica.  Principalmente&nbsp;<strong>ALK-negativo<\/strong>,&nbsp;<strong>CD30-positivo<\/strong>,&nbsp;<strong>EMA negativo<\/strong><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Morphologie\"><\/span><strong>Morfologia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li>As carater\u00edsticas s\u00e3o&nbsp;<strong>\u201eC\u00e9lulas Hallmark\u201c<\/strong>, c\u00e9lulas anapl\u00e1sicas grandes, com n\u00facleos em forma de ferradura localizados excentricamente e&nbsp;<strong>branqueamento eosinof\u00edlico paranuclear<\/strong>.<\/li>\n\n\n\n<li>Variantes morfol\u00f3gicas:&nbsp;<strong>comum<\/strong>,&nbsp;<strong>linfo-histioc\u00edtico<\/strong>,&nbsp;<strong>Tipo Hodgkin<\/strong>,&nbsp;<strong>c\u00e9lula pequena<\/strong>&nbsp;(frequentemente mal diagnosticada) e&nbsp;<strong>Tipos de combina\u00e7\u00e3o<\/strong><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-16\"><\/span>Diagn\u00f3stico diferencial<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico baseia-se numa combina\u00e7\u00e3o de&nbsp;<strong>an\u00e1lises morfol\u00f3gicas, imunohistoqu\u00edmicas e de biologia molecular<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Imunohistoqu\u00edmica (IHC)<\/strong><br>- <strong>Positivo<\/strong>CD30 (constante), CD2, CD3, CD5, CD7, CD45RO, granzima B, perforina, TIA-1, EMA (apenas para ALK+).<br>- <strong>Express\u00e3o de ALK<\/strong> - N\u00facleo positivo em ALK+ ALCL;&nbsp;<strong>Diferencia\u00e7\u00e3o central<\/strong>&nbsp;de ALK- ALCL<\/li>\n\n\n\n<li><strong>Biologia molecular<\/strong><br>- <strong>PEIXE<\/strong>&nbsp;e&nbsp;<strong>PCR<\/strong>: Prova da&nbsp;<strong>t(2;5)(p23;q35)<\/strong>-transloca\u00e7\u00e3o (NPM-ALK) em ALK+ ALCL<br>- <strong>NGS<\/strong>Identifica rearranjos relevantes para o progn\u00f3stico<br>\u2013 \u2013 <strong>Rearranjo DUSP22\/IRF4<\/strong>&nbsp;\u2192 Melhor progn\u00f3stico<br>\u2013 \u2013 <strong>Rearranjo de TP63<\/strong>&nbsp;\u2192 pior progn\u00f3stico<\/li>\n\n\n\n<li><strong>Diagn\u00f3sticos diferenciais<\/strong><br>- <strong>Linfoma de Hodgkin<\/strong>CD30+ e CD15+; mas&nbsp;<strong>CD20+<\/strong>,&nbsp;<strong>CD30-<\/strong>&nbsp;para c\u00e9lulas Reed-Sternberg,&nbsp;<strong>ALK-negativo<\/strong>.<br>- <strong>Linfoma anapl\u00e1sico de grandes c\u00e9lulas B (ABC)<\/strong>CD20+ (em compara\u00e7\u00e3o com CD30+ para ALCL),&nbsp;<strong>CD30-<\/strong>,&nbsp;<strong>ALK-negativo<\/strong><br>- <strong>Linfomas cut\u00e2neos prim\u00e1rios CD30-positivos<\/strong><br>\u2013 \u2013 <strong>ALK-negativo<\/strong>,&nbsp;<strong>EMA-negativo<\/strong>,&nbsp;<strong>Previs\u00e3o mais favor\u00e1vel<\/strong><br>- <strong>Linfoma angioimunobl\u00e1stico de c\u00e9lulas T (AITL)<\/strong><br>\u2013 \u2013 <strong>Fen\u00f3tipo do fol\u00edculo T auxiliar<\/strong>,&nbsp;<strong>Muta\u00e7\u00f5es TET2\/RHOA\/IDH2<\/strong>,&nbsp;<strong>Coombs-positivo<\/strong>,&nbsp;<strong>Hipergamaglobulinemia policlonal<\/strong><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-15\"><\/span>Terapia<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>ALCL sist\u00e9mico (ALK+)<\/strong><br>- <strong>padr\u00e3o<\/strong>:&nbsp;<strong>Terapia CHOP<\/strong>&nbsp;(ciclofosfamida, doxorrubicina, vincristina, prednisona)<br>- <strong>Combina\u00e7\u00e3o com brentuximab vedotina (BV)<\/strong>:&nbsp;<strong>Elevada taxa de resposta (86 %)<\/strong>, melhorado&nbsp;<strong>Sobreviv\u00eancia global e livre de doen\u00e7a<\/strong>&nbsp;(Estudo ECHELON-2)<\/li>\n\n\n\n<li><strong>ALK- ALCL<\/strong><br>- Menos sens\u00edvel ao CHOP;&nbsp;<strong>Combina\u00e7\u00e3o BV<\/strong>&nbsp;\u00e9 uma op\u00e7\u00e3o terap\u00eautica central<br>Novas abordagens:<br>- <strong>5-Azacitidina<\/strong>&nbsp;(desmetila\u00e7\u00e3o)<br>- <strong>C\u00e9lulas CAR-T<\/strong>&nbsp;contra CD30<\/li>\n\n\n\n<li><strong>BIA-ALCL<\/strong><br>- <strong>Remo\u00e7\u00e3o do implante e da c\u00e1psula<\/strong>;&nbsp;<strong>tratamento quimioterap\u00eautico de acompanhamento<\/strong>&nbsp;em caso de dissemina\u00e7\u00e3o (por exemplo, CHOP + BV)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-14\"><\/span>Previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>ALK+ ALCL<\/strong><br><strong>Favor\u00e1vel<\/strong>&nbsp;- Taxa de sobreviv\u00eancia a 5 anos&nbsp;<strong>70-90 %<\/strong><\/li>\n\n\n\n<li><strong>ALK- ALCL<\/strong><br><strong>Menos favor\u00e1vel<\/strong>&nbsp;- Taxa de sobreviv\u00eancia a 5 anos&nbsp;<strong>40-60 %<\/strong><\/li>\n\n\n\n<li><strong>cALCL<\/strong><br><strong>Muito bom<\/strong>&nbsp;- Taxa de sobreviv\u00eancia a 10 anos &gt;90 %<\/li>\n\n\n\n<li><strong>BIA-ALCL<\/strong><br><strong>Favor\u00e1vel<\/strong>, se for reconhecido e tratado precocemente (remo\u00e7\u00e3o de implantes)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>Subclassifica\u00e7\u00e3o biol\u00f3gica molecular<\/strong>&nbsp;(ALK, DUSP22, TP63) \u00e9 crucial para o progn\u00f3stico e o planeamento da terap\u00eautica.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Mycosis_fungoides\"><\/span><strong>Micose fung\u00f3ide<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong><br>Micose fung\u00f3ide<\/strong>&nbsp;\u00e9 o linfoma cut\u00e2neo prim\u00e1rio de c\u00e9lulas T mais comum, uma forma de linfoma n\u00e3o-Hodgkin que afecta principalmente a pele.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Caracteriza-se por uma prolifera\u00e7\u00e3o clonal de linf\u00f3citos T at\u00edpicos na pele e pertence aos linfomas cut\u00e2neos de c\u00e9lulas T, que representam cerca de 70 % de todos os linfomas cut\u00e2neos prim\u00e1rios.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild_und_klinisch-morphologische_Merkmale\"><\/span>Quadro cl\u00ednico e carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">A doen\u00e7a evolui normalmente em tr\u00eas fases:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Fase do eczema<\/strong><br>Focos (manchas) eritemato-escamosos cr\u00f3nicos, com comich\u00e3o, bem definidos, que podem persistir durante anos ou d\u00e9cadas<\/li>\n\n\n\n<li><strong>Fase de infiltra\u00e7\u00e3o<\/strong><br>Crescimento de placas acastanhadas e elevadas em focos existentes, muitas vezes com \u00e1reas preservadas de pele saud\u00e1vel&nbsp;<\/li>\n\n\n\n<li><strong>Estadio do tumor<\/strong><br>Forma\u00e7\u00e3o de tumores hemisf\u00e9ricos, ulcerados, que tendem a tornar-se superinfectados e podem levar a um processo de generaliza\u00e7\u00e3o com envolvimento de g\u00e2nglios linf\u00e1ticos e \u00f3rg\u00e3os (f\u00edgado, ba\u00e7o, pulm\u00f5es, SNC).&nbsp;<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Variantes<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Micose fung\u00f3ide foliculotr\u00f3pica (FMF)<\/strong><br>Caracteriza-se por p\u00e1pulas c\u00f3rneas folicularmente acentuadas, c\u00f3nicas e pontiagudas, da cor da pele, frequentemente com alopecia (por exemplo, sobrancelhas, linha do cabelo), les\u00f5es semelhantes a acne e quistos na face e no pesco\u00e7o. A epiderme geralmente n\u00e3o \u00e9 afetada (\u201eepiderme lisa superficial\u201c)<\/li>\n\n\n\n<li><strong>Reticulose pagetoide<\/strong><br>Les\u00f5es localizadas e demarcadas com forte prolifera\u00e7\u00e3o intra-epid\u00e9rmica de c\u00e9lulas T neopl\u00e1sicas, principalmente nas extremidades<\/li>\n\n\n\n<li><strong>Pele fl\u00e1cida granulomatosa (GSS)<\/strong><br>Forma rara com pele fl\u00e1cida e pendular nas grandes pregas cut\u00e2neas, acompanhada por altera\u00e7\u00f5es granulomatosas dos tecidos e perda de fibras el\u00e1sticas. O progn\u00f3stico \u00e9 pior do que no caso da MF cl\u00e1ssica.<\/li>\n\n\n\n<li><strong>Micose fung\u00f3ide hipopigmentada<\/strong>Variante poiquilod\u00e9rmica com bom progn\u00f3stico.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_-methodik-3\"><\/span>Diagn\u00f3stico diferencial e metodologia<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico \u00e9 um desafio, uma vez que o quadro cl\u00ednico \u00e9 frequentemente at\u00edpico e o tempo m\u00e9dio entre a manifesta\u00e7\u00e3o inicial e o diagn\u00f3stico \u00e9 de 3-4 anos. O fator decisivo \u00e9 a&nbsp;<strong>provas histopatol\u00f3gicas<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Carater\u00edsticas histol\u00f3gicas<\/strong><br>Infiltrado linfocit\u00e1rio em forma de faixa na derme superior e&nbsp;<strong>Microabscessos de Pautrier<\/strong>&nbsp;na epiderme<\/li>\n\n\n\n<li><strong>Imunohistologia<\/strong><br>CD3+, CD4+, CD8-, CD45Ro+, CD45Ra- (fen\u00f3tipo de auxiliar T de mem\u00f3ria). O CD30 pode ser positivo em fases avan\u00e7adas<\/li>\n\n\n\n<li><strong>Biologia molecular<\/strong><br>Rearranjo clonal do gene do recetor das c\u00e9lulas T (pode estar ausente nas les\u00f5es iniciais)<\/li>\n\n\n\n<li><strong>Imagiologia<\/strong><br>TC, RMN, PET-CT para exame de estadiamento (especialmente em casos de suspeita de envolvimento extracut\u00e2neo)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Diagn\u00f3sticos diferenciais<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>S\u00edndrome de S\u00e9zary<\/strong><br>Eritrodermia (&gt;80 % de superf\u00edcie corporal), linfadenopatia, c\u00e9lulas de S\u00e9zary no sangue perif\u00e9rico.<\/li>\n\n\n\n<li><strong>Urtic\u00e1ria pigmentosa<\/strong><br>Manchas cinzento-acastanhadas com rea\u00e7\u00e3o urticariforme (ausente na MF)<\/li>\n\n\n\n<li><strong>Tinha corporal<\/strong><br>Incha\u00e7o marginal, descama\u00e7\u00e3o, evid\u00eancia cultural de fungos<\/li>\n\n\n\n<li><strong>Outros linfomas cut\u00e2neos de c\u00e9lulas T<\/strong><br>Sem evolu\u00e7\u00e3o faseada, principalmente forma\u00e7\u00e3o de n\u00f3dulos prim\u00e1rios<\/li>\n\n\n\n<li><strong>Linfomas cut\u00e2neos prim\u00e1rios de c\u00e9lulas B<\/strong><br>A sequ\u00eancia f\u00e1sica tamb\u00e9m est\u00e1 ausente aqui; evid\u00eancia histol\u00f3gica<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-16\"><\/span>Terapia<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O tratamento depende da fase da doen\u00e7a:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Fase inicial (patches\/placas)<\/strong><br>Terapia local com&nbsp;<strong>PUVA<\/strong>,&nbsp;<strong>UVB de banda estreita<\/strong>, glucocorticoide externo ou&nbsp;<strong>radioterapia t\u00f3pica agressiva<\/strong>&nbsp;(especialmente com FMF)<\/li>\n\n\n\n<li><strong>Fase avan\u00e7ada<\/strong><br>Combina\u00e7\u00e3o de&nbsp;<strong>PUVA + retin\u00f3ides<\/strong>&nbsp;(por exemplo, acitretina &gt;10 mg\/dia),&nbsp;<strong>Interfer\u00e3o-\u03b1<\/strong>, irradia\u00e7\u00e3o local com raios X (3-5 Gy).&nbsp;<\/li>\n\n\n\n<li><strong>Fase IIb e seguintes<\/strong><br>Quimioterapia (CHOP, doxorrubicina, gemcitabina)<br>experimental:&nbsp;<strong>Transplante alog\u00e9nico de c\u00e9lulas estaminais<\/strong><\/li>\n\n\n\n<li><strong>Terapia paliativa no est\u00e1dio do tumor<\/strong><br>Clorambucil ou poliquimioterapia<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-15\"><\/span>Previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Fase inicial<\/strong><br>Bom progn\u00f3stico, remiss\u00e3o poss\u00edvel, esperan\u00e7a m\u00e9dia de vida 7-10 anos ap\u00f3s o diagn\u00f3stico<\/li>\n\n\n\n<li><strong>Fase avan\u00e7ada<\/strong><br>Progn\u00f3stico significativamente pior; taxa de sobreviv\u00eancia a 5 anos para FMF no est\u00e1dio IIA: 87 %, para IIb: 83 %<\/li>\n\n\n\n<li><strong>GSS<\/strong>*<br>Taxa de sobreviv\u00eancia a 5 anos cerca de 60 %<br>*<strong>Pele frouxa granulomatosa<\/strong> - uma variante muito rara da micose fung\u00f3ide (MF), que \u00e9 classificada como linfoma cut\u00e2neo prim\u00e1rio de c\u00e9lulas T<\/li>\n\n\n\n<li><strong>Transforma\u00e7\u00e3o em linfoma de grandes c\u00e9lulas<\/strong>&nbsp;(cerca de 25 % de caixas)<br>Piora significativamente o progn\u00f3stico<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Factores de progn\u00f3stico<\/strong><br>Est\u00e1dio no momento do diagn\u00f3stico, extens\u00e3o do envolvimento da pele, envolvimento dos g\u00e2nglios linf\u00e1ticos, manifesta\u00e7\u00f5es extracut\u00e2neas.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Uma terapia precoce e agressiva melhora a qualidade de vida e atrasa a progress\u00e3o da doen\u00e7a.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Sezary-Syndrom\"><\/span>S\u00edndrome de S\u00e9zary<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>S\u00edndrome de S\u00e9zary (SS)<\/strong>&nbsp;\u00e9 uma forma agressiva de linfoma cut\u00e2neo prim\u00e1rio de c\u00e9lulas T (CTCL) e caracteriza-se pela cl\u00e1ssica&nbsp;<strong>Tr\u00edade de eritrodermia, linfadenopatia generalizada e linf\u00f3citos T at\u00edpicos circulantes (c\u00e9lulas de S\u00e9zary)<\/strong>&nbsp;no sangue perif\u00e9rico.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u00c9 a variante leuc\u00e9mica do linfoma cut\u00e2neo de c\u00e9lulas T e ocorre tipicamente na 5\u00aa d\u00e9cada de vida, sendo mais frequente nos homens. A doen\u00e7a progride mais rapidamente do que a micose fung\u00f3ide e tem um progn\u00f3stico desfavor\u00e1vel.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild-3\"><\/span>Imagem cl\u00ednica<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Manifesta\u00e7\u00f5es cut\u00e2neas<\/strong>Incluir um&nbsp;<strong>eritrodermia escamosa e generalizada<\/strong>&nbsp;com prurido intenso (prurido), muitas vezes acompanhado de&nbsp;<strong>Alop\u00e9cia<\/strong>&nbsp;(queda de cabelo),&nbsp;<strong>Malforma\u00e7\u00f5es das unhas (onicodistrofia)<\/strong>,&nbsp;<strong>hiperqueratose palmoplantar<\/strong>&nbsp;e&nbsp;<strong>Ectropiona<\/strong>&nbsp;(desloca\u00e7\u00e3o da p\u00e1lpebra).  A pele pode&nbsp;<strong>Facies leontina<\/strong>&nbsp;(cara de le\u00e3o).&nbsp;<\/li>\n\n\n\n<li><strong>Sintomas sist\u00e9micos<\/strong>As queixas mais comuns s\u00e3o&nbsp;<strong>Cansa\u00e7o geral, sensa\u00e7\u00e3o de frio e tremores<\/strong>.  Outros sinais s\u00e3o&nbsp;<strong>Hepatoesplenomegalia<\/strong>&nbsp;e aumento dos g\u00e2nglios linf\u00e1ticos.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Morphologie-2\"><\/span>Morfologia<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Carater\u00edsticas morfol\u00f3gicas das c\u00e9lulas de S\u00e9zary<\/strong><br>Caracterizado por&nbsp;<strong>n\u00facleos cerebriformes (convolutos)<\/strong>, s\u00e3o normalmente&nbsp;<strong>CD4-positivo, CD7- e CD26-negativo<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">As c\u00e9lulas em circula\u00e7\u00e3o s\u00e3o detectadas no sangue, pelo que \u00e9 efectuada uma&nbsp;<strong>N\u00famero de \u22651000 c\u00e9lulas de S\u00e9zary\/mm\u00b3<\/strong>&nbsp;\u00e9 considerado diagn\u00f3stico.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-17\"><\/span>Diagn\u00f3stico diferencial<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial da s\u00edndrome de S\u00e9zary \u00e9 crucial, uma vez que pode ser confundida cl\u00ednica e histologicamente com outras doen\u00e7as.<br><strong>Diagn\u00f3sticos diferenciais importantes:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Micose fung\u00f3ide<\/strong>&nbsp;(forma mais comum de CTCL)<br>A diferencia\u00e7\u00e3o baseia-se principalmente nos&nbsp;<strong>Envolvimento do sangue<\/strong>&nbsp;(para SS, n\u00e3o para as fases iniciais de MF)<\/li>\n\n\n\n<li><strong>Dermatoses inflamat\u00f3rias<\/strong><br>- <strong>Dermatite at\u00f3pica (neurodermatite)<\/strong>,<br>- <strong>Psor\u00edase<\/strong><br>- <strong>Pitir\u00edase rubra pilar<\/strong><\/li>\n\n\n\n<li><strong>Outros linfomas cut\u00e2neos<\/strong><br>Outros subtipos prim\u00e1rios de CTCL, tais como MF foliculotr\u00f3pica, reticulose paget\u00f3ide.&nbsp;<\/li>\n\n\n\n<li><strong>Efeitos secund\u00e1rios dos medicamentos<\/strong>&nbsp;e&nbsp;<strong>Doen\u00e7as sist\u00e9micas<\/strong>&nbsp;com manifesta\u00e7\u00f5es eritrod\u00e9rmicas<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methodik-3\"><\/span><strong>Metodologia de diagn\u00f3stico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Exame cl\u00ednico<\/strong>&nbsp;centrando-se nas altera\u00e7\u00f5es cut\u00e2neas, nos g\u00e2nglios linf\u00e1ticos e na contagem sangu\u00ednea.<\/li>\n\n\n\n<li><strong>Histopatologia da biopsia cut\u00e2nea<\/strong><br>apresenta frequentemente um quadro inespec\u00edfico de \u201epseudo-dermatite\u201c na fase inicial; na fase avan\u00e7ada&nbsp;<strong>n\u00facleos cerebriformes<\/strong>&nbsp;e&nbsp;<strong>Infiltrados em forma de banda<\/strong>&nbsp;vis\u00edvel<\/li>\n\n\n\n<li><strong>Citometria de fluxo do sangue perif\u00e9rico<\/strong><br>Prova de&nbsp;<strong>C\u00e9lulas T CD4+\/CD8- com negatividade para CD7 e CD26<\/strong>&nbsp;e&nbsp;<strong>R\u00e1cio CD4\/CD8 \u226510<\/strong><\/li>\n\n\n\n<li><strong>An\u00e1lises biol\u00f3gicas moleculares<\/strong><br><strong>Prova de clonalidade<\/strong>&nbsp;(PCR do gene do recetor de c\u00e9lulas T) no sangue e na pele, como&nbsp;<strong>Expans\u00e3o clonal de c\u00e9lulas T<\/strong>&nbsp;uma carater\u00edstica central \u00e9<\/li>\n\n\n\n<li><strong>Procedimentos de imagiologia<\/strong><br>Sonografia, TAC, PET-CT para estadiamento e dete\u00e7\u00e3o de envolvimento extracut\u00e2neo.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-17\"><\/span>Terapia<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">A terapia \u00e9&nbsp;<strong>Dependente do est\u00e1dio e maioritariamente paliativo<\/strong>, com o objetivo de controlar os sintomas e atrasar a progress\u00e3o.&nbsp;<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Primeira linha<\/strong><br>- <strong>Terapia PUVA<\/strong>&nbsp;(Psoraleno + UV-A)<br>- <strong>Fotoferese extracorporal (ECP)<\/strong> Particularmente eficaz para SS<br>- <strong>Ester\u00f3ides t\u00f3picos ou retin\u00f3ides<\/strong>&nbsp;(por exemplo, Bexarotene)<br>- <strong>Terapia combinada<\/strong> - PCE com&nbsp;<strong>metotrexato em dose baixa<\/strong>,&nbsp;<strong>Interfer\u00e3o-alfa<\/strong>&nbsp;ou&nbsp;<strong>Bexaroteno<\/strong>&nbsp;<\/li>\n\n\n\n<li><strong>Segunda linha (avan\u00e7ado \/ resistente \u00e0 terap\u00eautica)<\/strong><br>- <strong>Quimioterapia<\/strong>&nbsp;com&nbsp;<strong>doxorrubicina liposs\u00f3mica<\/strong>,&nbsp;<strong>Gemcitabina<\/strong>,&nbsp;<strong>Alemtuzumab<\/strong><br>- <strong>Anticorpos monoclonais<\/strong> - <strong>Mogamulizumab<\/strong>&nbsp;(anti-CCR4) autorizado na UE desde 2018<\/li>\n\n\n\n<li><strong>Op\u00e7\u00f5es de terapia radical<\/strong><br>- <strong>Transplante alog\u00e9nico de c\u00e9lulas estaminais<\/strong>&nbsp;em doentes mais jovens com uma evolu\u00e7\u00e3o resistente \u00e0 terap\u00eautica<br>- <strong>Terapia de feixe de electr\u00f5es em toda a pele<\/strong>&nbsp;com progress\u00e3o local<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-16\"><\/span>Previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O progn\u00f3stico da s\u00edndrome de S\u00e9zary \u00e9&nbsp;<strong>desfavor\u00e1vel<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Sobreviv\u00eancia m\u00e9dia de cerca de 5 anos<\/strong><\/li>\n\n\n\n<li>O tempo de sobreviv\u00eancia \u00e9 determinado por&nbsp;<strong>Sintomas iniciais, envolvimento sangu\u00edneo e progress\u00e3o da doen\u00e7a<\/strong>&nbsp;influenciado<\/li>\n\n\n\n<li>O&nbsp;<strong>A taxa de sobreviv\u00eancia a 5 anos \u00e9 de cerca de 50 %<\/strong>&nbsp;<\/li>\n\n\n\n<li>Um&nbsp;<strong>Pior progn\u00f3stico<\/strong>&nbsp;em compara\u00e7\u00e3o com a micose fung\u00f3ide, especialmente em fases avan\u00e7adas e com uma contagem elevada de c\u00e9lulas de S\u00e9zary no sangue<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico da s\u00edndrome de S\u00e9zary requer um&nbsp;<strong>abordagem multimodal<\/strong>&nbsp;com cl\u00ednica, histologia, citometria de fluxo e an\u00e1lise de clonalidade biol\u00f3gica molecular.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A terapia \u00e9 complexa e dependente do est\u00e1dio, com novas abordagens, como o mogamulizumab e o transplante de c\u00e9lulas estaminais, a expandir as op\u00e7\u00f5es de tratamento.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Apesar dos progressos, o progn\u00f3stico continua a ser limitado.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"PKAGL\"><span class=\"ez-toc-section\" id=\"Primar_kutanes_anaplastisches_groszelliges_CD30-positives_Lymphom_cALCL\"><\/span>Linfoma cut\u00e2neo prim\u00e1rio anapl\u00e1sico de grandes c\u00e9lulas CD30-positivo (cALCL)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O linfoma prim\u00e1rio cut\u00e2neo anapl\u00e1sico de grandes c\u00e9lulas CD30-positivo (cALCL) \u00e9 uma forma rara mas clinicamente benigna de linfoma cut\u00e2neo que difere significativamente do ALCL sist\u00e9mico.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Ocorre&nbsp;<strong>Predominantemente em homens com mais de 60 anos<\/strong>&nbsp;e caracteriza-se por&nbsp;<strong>N\u00f3dulos ou placas de crescimento r\u00e1pido, frequentemente solit\u00e1rios ou agrupados<\/strong>&nbsp;caracterizados, que frequentemente&nbsp;<strong>ulcerar<\/strong>&nbsp;pode.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Em alguns casos, um&nbsp;<strong>regress\u00e3o espont\u00e2nea<\/strong>&nbsp;poss\u00edvel. A previs\u00e3o \u00e9&nbsp;<strong>muito bom<\/strong>, com um&nbsp;<strong>Taxa de sobreviv\u00eancia de 10 anos superior a 90 %<\/strong>.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_und_morphologisches_Bild-2\"><\/span>Quadro cl\u00ednico e morfol\u00f3gico<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cl\u00ednica<\/strong><br>N\u00f3dulos ou placas vermelhas, vermelho-acastanhadas ou vermelho-azuladas, lisas, frequentemente na cabe\u00e7a, no pesco\u00e7o ou no corpo.&nbsp;<\/li>\n\n\n\n<li><strong>Histol\u00f3gico<\/strong><br>Infiltrados difusos na derme e no subcut\u00e2neo superior, a epiderme permanece normalmente livre<br>As c\u00e9lulas tumorais apresentam&nbsp;<strong>carater\u00edsticas anapl\u00e1sicas<\/strong>:<br>n\u00facleo em forma de ferradura, disposto de forma exc\u00eantrica, zona perinuclear eosinof\u00edlica no citoplasma<\/li>\n\n\n\n<li><strong>Imunofen\u00f3tipo<\/strong><br>- <strong>CD30-positivo<\/strong>&nbsp;(constante)<br>- <strong>ALK-negativo<\/strong><br>- <strong>EMA-negativo<\/strong><br>- <strong>CD2, CD3, CD5, CD7, CD45RO<\/strong>&nbsp;positivo (fen\u00f3tipo de c\u00e9lulas T)<br>- Sem express\u00e3o da prote\u00edna ALK, que diferencia o ALCL sist\u00e9mico<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_-methodik-4\"><\/span>Diagn\u00f3stico diferencial e metodologia<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial \u00e9 crucial, uma vez que podem existir sobreposi\u00e7\u00f5es cl\u00ednicas e histol\u00f3gicas.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Diagn\u00f3sticos diferenciais importantes:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Linfoma anapl\u00e1sico sist\u00e9mico de grandes c\u00e9lulas (sALCL)<\/strong><br>A diferencia\u00e7\u00e3o \u00e9 feita por&nbsp;<strong>Aus\u00eancia de manifesta\u00e7\u00f5es extracut\u00e2neas<\/strong>&nbsp;(medula \u00f3ssea, g\u00e2nglios linf\u00e1ticos, \u00f3rg\u00e3os) para cALCL<br><strong>Estado da ALK<\/strong>&nbsp;\u00e9 decisivo: sALCL \u00e9 frequentemente ALK-positivo, cALCL ALK-negativo<\/li>\n\n\n\n<li><strong>Linfoma difuso de grandes c\u00e9lulas B (DLBCL)<\/strong><br>Les\u00f5es clinicamente semelhantes. Diferencia\u00e7\u00e3o por&nbsp;<strong>fen\u00f3tipo de c\u00e9lulas B negativas (CD20-, CD79a-, CD10-)<\/strong>,&nbsp;<strong>CD30 positivo<\/strong>&nbsp;no cALCL<br>Dete\u00e7\u00e3o molecular de um&nbsp;<strong>rearranjo clonal da cadeia pesada de imunoglobulina<\/strong>&nbsp;Ajuda no DLBCL<\/li>\n\n\n\n<li><strong>Pseudolinfomas reactivos de c\u00e9lulas B (B-PSL)<\/strong><br>Infiltrados histologicamente semelhantes, mas&nbsp;<strong>n\u00e3o clonais<\/strong>,&nbsp;<strong>CD30-negativo<\/strong>,&nbsp;<strong>sem anaplasia<\/strong><\/li>\n\n\n\n<li><strong>Micose fung\u00f3ide (MF)<\/strong><br>Pode estar associado a c\u00e9lulas CD30-positivas.<br>Diferencia\u00e7\u00e3o atrav\u00e9s de&nbsp;<strong>Fen\u00f3tipo das c\u00e9lulas T (CD4+, CD5-, CD7-)<\/strong><br><strong>sem express\u00e3o de CD30<\/strong>&nbsp;com MF cl\u00e1ssico<\/li>\n\n\n\n<li><strong>Linfoma cut\u00e2neo com pseudolinfomas CD30-positivos (LPE)<\/strong><br>Imagens semelhantes do ponto de vista cl\u00ednico e histol\u00f3gico.<br>O diagn\u00f3stico requer&nbsp;<strong>Combina\u00e7\u00e3o de quadro cl\u00ednico, morfologia histol\u00f3gica e imunofenotipagem<\/strong>.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-18\"><\/span>Terapia<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Prim\u00e1rio<\/strong><br><strong>Irradia\u00e7\u00e3o<\/strong>&nbsp;(\u00fanica ou localizada) ou&nbsp;<strong>Excis\u00e3o<\/strong>&nbsp;para les\u00f5es solit\u00e1rias<\/li>\n\n\n\n<li><strong>Alternativa<\/strong><br><strong>Rituximab<\/strong>&nbsp;(anticorpos monoclonais anti-CD20),&nbsp;<strong>Interfer\u00e3o-alfa (dose baixa)<\/strong><\/li>\n\n\n\n<li><strong>Poliquimioterapia (por exemplo, esquema CHOP)<\/strong>&nbsp;Apenas necess\u00e1rio para les\u00f5es m\u00faltiplas ou recorrentes, raramente necess\u00e1rio<\/li>\n\n\n\n<li><strong>Nenhum<\/strong>&nbsp;Quimioterapia sist\u00e9mica para envolvimento cut\u00e2neo isolado<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-17\"><\/span>Previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Muito bom<\/strong> - Taxa de sobreviv\u00eancia a 10 anos &gt; 90 %<\/li>\n\n\n\n<li><strong>As met\u00e1stases extracut\u00e2neas s\u00e3o extremamente raras<\/strong><\/li>\n\n\n\n<li><strong>Recorr\u00eancias<\/strong>&nbsp;podem ocorrer, mas s\u00e3o geralmente localizadas e facilmente trat\u00e1veis<\/li>\n\n\n\n<li><strong>Transforma\u00e7\u00e3o em formas altamente malignas<\/strong>&nbsp;\u00e9 muito raro<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico requer um&nbsp;<strong>abordagem multimodal<\/strong>:&nbsp;<strong>Avalia\u00e7\u00e3o cl\u00ednica, exame histol\u00f3gico, imunohistoqu\u00edmica (especialmente CD30, ALK, CD20, CD3, CD45RO)<\/strong>&nbsp;e, se necess\u00e1rio&nbsp;<strong>An\u00e1lises biol\u00f3gicas moleculares (por exemplo, rearranjo clonal de imunoglobulinas)<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A diferencia\u00e7\u00e3o do ALCL sist\u00e9mico \u00e9 crucial para a terapia e o progn\u00f3stico.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"KML\"><span class=\"ez-toc-section\" id=\"Kutanes_Marginalzonen-Lymphom\"><\/span><strong>Linfoma cut\u00e2neo da zona marginal<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O <strong>Linfoma cut\u00e2neo prim\u00e1rio da zona marginal (PCMZL)<\/strong>&nbsp;\u00e9 um linfoma de c\u00e9lulas B pouco maligno que ocorre principalmente na pele e se caracteriza por uma evolu\u00e7\u00e3o benigna e de crescimento lento.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Representa um equivalente cut\u00e2neo dos linfomas MALT (tecido linfoide associado \u00e0 mucosa), pelo que \u00e9 ocasionalmente designado por&nbsp;<strong>Linfoma SALT<\/strong>&nbsp;(tecido linfoide associado \u00e0 pele).&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild_und_klinisch-morphologische_Merkmale-2\"><\/span><strong>Quadro cl\u00ednico e carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Apresenta\u00e7\u00e3o<\/strong><br>Tipicamente como&nbsp;<strong>p\u00e1pulas, placas ou infiltrados nodulares m\u00faltiplos, isolados ou agrupados<\/strong>&nbsp;para o&nbsp;<strong>Extremidades, tronco ou pesco\u00e7o<\/strong><\/li>\n\n\n\n<li><strong>Aspeto cl\u00ednico<\/strong><br>Altera\u00e7\u00f5es cut\u00e2neas vermelho-acastanhadas, bem definidas, frequentemente ligeiramente escamosas ou endurecidas, com progress\u00e3o lenta em termos de tamanho<\/li>\n\n\n\n<li><strong>Carater\u00edsticas histol\u00f3gicas<\/strong><br>Infiltrados nodulares a difusos de&nbsp;<strong>linf\u00f3citos de tamanho pequeno a m\u00e9dio<\/strong>, que se localizam principalmente na derme.<br>As c\u00e9lulas tumorais s\u00e3o&nbsp;<strong>bcl-2-positivo<\/strong>, n\u00e3o apresentam epidermotropismo e exibem carater\u00edsticas&nbsp;<strong>Estruturas do tipo zona marginal<\/strong>&nbsp;sobre.<br>O imunohistograma mostra&nbsp;<strong>CD20+, CD79a+, CD5-, CD10-, CD23-<\/strong>&nbsp;e&nbsp;<strong>imunoglobulinas de membrana<\/strong>&nbsp;expresso<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_-methodik-5\"><\/span><strong>Diagn\u00f3stico diferencial e metodologia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial \u00e9 dif\u00edcil devido \u00e0 semelhan\u00e7a morfol\u00f3gica com processos reactivos e outros linfomas cut\u00e2neos.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Os diagn\u00f3sticos diferenciais importantes incluem<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Pseudolinfomas reactivos de c\u00e9lulas B (B-PSL)<\/strong><br>Frequentemente dif\u00edcil de distinguir cl\u00ednica e histologicamente<br>O fator decisivo \u00e9 a&nbsp;<strong>Correla\u00e7\u00e3o cl\u00ednico-patol\u00f3gica<\/strong>&nbsp;e o&nbsp;<strong>Prova de clonalidade<\/strong>&nbsp;(por exemplo, por PCR para rearranjos clonais da cadeia pesada da imunoglobulina)<\/li>\n\n\n\n<li><strong>Linfoma folicular (PCFCL)<\/strong><br>Podem ser morfologicamente semelhantes<br>Diferencia\u00e7\u00e3o por imunohistoqu\u00edmica (por exemplo, express\u00e3o de BCL6, CD10)<\/li>\n\n\n\n<li><strong>Linfoma difuso de grandes c\u00e9lulas B (DLBCL)<\/strong><br>Apresenta um padr\u00e3o de crescimento mais agressivo, c\u00e9lulas maiores, \u00edndice de prolifera\u00e7\u00e3o mais elevado (Ki-67) e \u00e9&nbsp;<strong>CD20+<\/strong>, mas frequentemente&nbsp;<strong>BCL2-positivo e MYC-positivo<\/strong>&nbsp;(linfoma de dupla les\u00e3o)<\/li>\n\n\n\n<li><strong>Centros de germina\u00e7\u00e3o reactivos<\/strong>&nbsp;nas doen\u00e7as inflamat\u00f3rias<br>Atrav\u00e9s de&nbsp;<strong>Imunohistoqu\u00edmica (por exemplo, CD10, BCL6, MUM1)<\/strong>&nbsp;e&nbsp;<strong>An\u00e1lise de clonalidade<\/strong>&nbsp;para delimitar<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostik-2\"><\/span><strong>Diagn\u00f3stico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Bi\u00f3psia atraum\u00e1tica de amostras de grandes \u00e1reas<\/strong>&nbsp;(pelo menos 4-6 mm) para uma avalia\u00e7\u00e3o histol\u00f3gica e imunohistoqu\u00edmica suficiente<\/li>\n\n\n\n<li><strong>Imunohistoqu\u00edmica<\/strong><br>CD20, CD79a, CD5, CD10, CD23, BCL6, MUM1, bcl-2, CD21 (para a rede FDC)<\/li>\n\n\n\n<li><strong>Dete\u00e7\u00e3o biol\u00f3gica molecular da clonalidade<\/strong><br>PCR ou Southern blot para genes de imunoglobulinas<\/li>\n\n\n\n<li><strong>Encena\u00e7\u00e3o<\/strong><br>Procedimentos de imagiologia (TC, PET-CT) para excluir o envolvimento extracut\u00e2neo, uma vez que o PCMZL \u00e9 principalmente cut\u00e2neo<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-19\"><\/span><strong>Terapia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Les\u00f5es assintom\u00e1ticas e limitadas<\/strong><br><strong>\u201eEstrat\u00e9gia de \u201cvigiar e esperar<\/strong>&nbsp;(observa\u00e7\u00e3o, sem terapia imediata)<\/li>\n\n\n\n<li><strong>Terapia local<\/strong><br><strong>Excis\u00e3o<\/strong>&nbsp;les\u00f5es individuais ou&nbsp;<strong>radioterapia local<\/strong>&nbsp;(por exemplo, 20-30 Gy).<\/li>\n\n\n\n<li><strong>Infesta\u00e7\u00e3o multifocal<\/strong><br>Terapia local em combina\u00e7\u00e3o com op\u00e7\u00f5es sist\u00e9micas, tais como&nbsp;<strong>Rituximab<\/strong>&nbsp;(anticorpo CD20),&nbsp;<strong>Imunomoduladores (por exemplo, interfer\u00e3o-\u03b1)<\/strong>&nbsp;ou&nbsp;<strong>Quimioterapia oral (por exemplo, clorambucil)<\/strong><\/li>\n\n\n\n<li><strong>Raro<\/strong> Necess\u00e1rio - Em caso de progress\u00e3o ou propaga\u00e7\u00e3o&nbsp;<strong>Quimioterapia sist\u00e9mica<\/strong>&nbsp;(por exemplo, R-CHOP)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-18\"><\/span><strong>Previs\u00e3o<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Muito bom<\/strong> - Taxas de sobreviv\u00eancia a cinco anos superiores a&nbsp;<strong>90 %<\/strong><\/li>\n\n\n\n<li>A doen\u00e7a progride&nbsp;<strong>lentamente progressivo<\/strong>, com recidivas raras e localizadas<\/li>\n\n\n\n<li><strong>As met\u00e1stases nos g\u00e2nglios linf\u00e1ticos ou nos \u00f3rg\u00e3os internos s\u00e3o raras<\/strong><\/li>\n\n\n\n<li><strong>Segundo linfoma<\/strong>&nbsp;(por exemplo, linfoma de Hodgkin) pode ocorrer em at\u00e9&nbsp;<strong>1\/3 dos casos<\/strong>&nbsp;e influenciam indiretamente o progn\u00f3stico<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico requer um&nbsp;<strong>Correla\u00e7\u00e3o cl\u00ednico-patol\u00f3gica exacta<\/strong>&nbsp;e n\u00e3o pode basear-se apenas em resultados de biologia molecular.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A atual diretriz S2k (2021) salienta o papel central da apresenta\u00e7\u00e3o cl\u00ednica na classifica\u00e7\u00e3o dos linfomas cut\u00e2neos.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Kutanes_Lymphom_mit_korniger_Mittelfingertatowierung\"><\/span><strong>Linfoma cut\u00e2neo com tatuagem granular do dedo m\u00e9dio<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O <strong>Linfoma cut\u00e2neo<\/strong>&nbsp;\u00e9 um grupo heterog\u00e9neo de doen\u00e7as malignas que se manifestam principalmente na pele e t\u00eam origem nos linf\u00f3citos T ou B.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A apresenta\u00e7\u00e3o cl\u00ednica pode variar muito e \u00e9 frequentemente inespec\u00edfica, o que dificulta o diagn\u00f3stico.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Um&nbsp;<strong>tatuagem granulada do dedo m\u00e9dio<\/strong>&nbsp;pode indicar uma altera\u00e7\u00e3o cut\u00e2nea local no contexto do linfoma cut\u00e2neo, especialmente se estiver associada a uma placa ou n\u00f3dulo de crescimento lento, avermelhado a acastanhado.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Esta altera\u00e7\u00e3o pode desenvolver-se ao longo de meses ou anos e \u00e9 normalmente&nbsp;<strong>N\u00e3o \u00e9 doloroso, mas muitas vezes d\u00e1 comich\u00e3o<\/strong>.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild_und_klinisch-morphologische_Merkmale-3\"><\/span>Quadro cl\u00ednico e carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Micose fung\u00f3ide (MF)<\/strong><br>a forma mais comum de linfoma cut\u00e2neo de c\u00e9lulas T (cerca de 75-80 %), progride tipicamente em tr\u00eas fases:<br>- <strong>Fase de remendo<\/strong><br>M\u00e1culas planas, bem definidas, eritematosas, ligeiramente escamosas (semelhantes ao eczema), geralmente no tronco, nos lados flexores das extremidades ou em partes do corpo sem exposi\u00e7\u00e3o solar<br>- <strong>Fase de placa<\/strong><br>Placas elevadas, avermelhadas-livres a acastanhadas, com escamas, crostas e liquenifica\u00e7\u00e3o; persistem frequentemente durante 2-5 anos<br>- <strong>Estadio do tumor<\/strong><br>Tumores hemisf\u00e9ricos ou lobulados, possivelmente com ulcera\u00e7\u00e3o e superinfe\u00e7\u00e3o; ocorre em 10-20 %<\/li>\n\n\n\n<li><strong>S\u00edndrome de S\u00e9zary (SS)<\/strong><br>Contraparte leuc\u00e9mica da MF com eritrodermia generalizada, prurido intenso, aumento dos g\u00e2nglios linf\u00e1ticos, distrofias das unhas e dete\u00e7\u00e3o de c\u00e9lulas linf\u00f3ides at\u00edpicas (c\u00e9lulas de S\u00e9zary) no sangue<\/li>\n\n\n\n<li><strong>Papulose linfomatosa (LyP)<\/strong><br>Caracterizada por p\u00e1pulas e n\u00f3dulos agrupados, espontaneamente regressivos, que desaparecem no espa\u00e7o de semanas<br>Histologicamente, v\u00e1rios tipos apresentam uma sobreposi\u00e7\u00e3o com o CTCL agressivo, raz\u00e3o pela qual a correla\u00e7\u00e3o cl\u00ednico-patol\u00f3gica \u00e9 crucial<\/li>\n\n\n\n<li><strong>Linfoma cut\u00e2neo prim\u00e1rio anapl\u00e1sico de grandes c\u00e9lulas (cALCL)<\/strong><br>N\u00f3dulos \u00fanicos, eritematosos a acastanhados, possivelmente com ulcera\u00e7\u00e3o<br>CD30-positivo, mas maioritariamente ALK-negativo<br>Regress\u00e3o espont\u00e2nea poss\u00edvel (aprox. 20 %)<\/li>\n\n\n\n<li><strong>Linfoma cut\u00e2neo prim\u00e1rio de c\u00e9lulas T acrais CD8-positivo (CD8+ ATCL)<\/strong><br>N\u00f3dulos solit\u00e1rios ou bilaterais em \u00e1reas acrais (por exemplo, rosto, orelhas, p\u00e9s)<br>Infiltrados histologicamente densos de linf\u00f3citos at\u00edpicos de tamanho pequeno a m\u00e9dio sem epidermotropia<br><strong>Excelente previs\u00e3o<\/strong>.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnose_und_Diagnostik\"><\/span>Diagn\u00f3stico diferencial e diagn\u00f3stico<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial \u00e9 crucial, uma vez que os linfomas cut\u00e2neos podem ser frequentemente confundidos com doen\u00e7as inflamat\u00f3rias ou benignas da pele:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Doen\u00e7as inflamat\u00f3rias da pele<\/strong><br>Psor\u00edase, eczema at\u00f3pico, dermatite de contacto, l\u00edquen plano<\/li>\n\n\n\n<li><strong>Linfoprolifera\u00e7\u00f5es benignas<\/strong><br>Pseudolinfomas, papulose linfomatosa (LyP)<\/li>\n\n\n\n<li><strong>Outras doen\u00e7as malignas<\/strong><br>Melanoma, carcinoma cut\u00e2neo de c\u00e9lulas de Merkel, linfoma cut\u00e2neo difuso de grandes c\u00e9lulas B (evolu\u00e7\u00e3o agressiva)<\/li>\n\n\n\n<li><strong>Doen\u00e7as infecciosas<\/strong><br>Tuberculose, lepra, infec\u00e7\u00f5es f\u00fangicas<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostikmethodik\"><\/span><strong>Metodologia de diagn\u00f3stico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Hist\u00f3ria m\u00e9dica e exame cl\u00ednico<\/strong><br>Evolu\u00e7\u00e3o a longo prazo, localiza\u00e7\u00e3o, sintomas (comich\u00e3o, dor)<\/li>\n\n\n\n<li><strong>Bi\u00f3psia da pele com an\u00e1lise histol\u00f3gica e imunohistoqu\u00edmica<\/strong><br>Dete\u00e7\u00e3o de c\u00e9lulas tumorais (CD3, CD4, CD8, CD30, genes TCR), epidermotropismo, clonalidade<\/li>\n\n\n\n<li><strong>An\u00e1lise de clonalidade<\/strong>&nbsp;(PCR para os genes TCR-gama ou IgH)<br>Confirma\u00e7\u00e3o da prolifera\u00e7\u00e3o neopl\u00e1sica<\/li>\n\n\n\n<li><strong>Procedimentos de imagiologia<\/strong><br>TAC, PET-CT, RMN para exames de estadiamento (g\u00e2nglios linf\u00e1ticos, \u00f3rg\u00e3os)<\/li>\n\n\n\n<li><strong>An\u00e1lises ao sangue<\/strong><br>Dete\u00e7\u00e3o de c\u00e9lulas de S\u00e9zary no sangue (para SS), LDH, SpSp s\u00e9rica<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-20\"><\/span>Terapia<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">A terapia \u00e9&nbsp;<strong>dependente da fase e da entidade<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Fases iniciais (mancha\/placa)<\/strong><br>Terapia t\u00f3pica (glucocortic\u00f3ides classe III-IV),&nbsp;<strong>Fototerapia (UVB, PUVA)<\/strong>, radioterapia local<\/li>\n\n\n\n<li><strong>Estadios avan\u00e7ados (est\u00e1dio do tumor, SS)<\/strong><br>Terap\u00eauticas sist\u00e9micas (retin\u00f3ides, interfer\u00e3o-\u03b1, citost\u00e1ticos),&nbsp;<strong>Terapias direcionadas<\/strong>&nbsp;como o mogamulizumab (CCR4), o brentuximab vedotin (CD30), os inibidores da histona desacetilase<\/li>\n\n\n\n<li><strong>Formas agressivas (por exemplo, linfoma cut\u00e2neo de c\u00e9lulas T \u03b3\/\u03b4)<\/strong><br>Poliquimioterapia, transplante de c\u00e9lulas estaminais hematopoi\u00e9ticas<\/li>\n\n\n\n<li><strong>Linfoma de c\u00e9lulas T acral CD8+<\/strong><br>A excis\u00e3o cir\u00fargica ou a radioterapia s\u00e3o suficientes;&nbsp;<strong>N\u00e3o \u00e9 necess\u00e1ria terapia sist\u00e9mica<\/strong><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-19\"><\/span>Previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Micose fung\u00f3ide<\/strong><br>Taxa de sobreviv\u00eancia de 5 anos 20-60 %; \u00e9 poss\u00edvel a dissemina\u00e7\u00e3o extracut\u00e2nea<\/li>\n\n\n\n<li><strong>S\u00edndrome de S\u00e9zary<\/strong><br>Mau progn\u00f3stico, tempo m\u00e9dio de sobreviv\u00eancia inferior a 3 anos<\/li>\n\n\n\n<li><strong>Papulose linfomatosa<\/strong><br><strong>Excelente previs\u00e3o<\/strong>, taxa de sobreviv\u00eancia a 5 e 10 anos pr\u00f3xima de 100 %<\/li>\n\n\n\n<li><strong>Linfoma de c\u00e9lulas T acral CD8+<\/strong><br><strong>Excelente previs\u00e3o<\/strong>, nenhuma morte conhecida devido \u00e0 doen\u00e7a<\/li>\n\n\n\n<li><strong>Linfoma cut\u00e2neo prim\u00e1rio anapl\u00e1sico de grandes c\u00e9lulas<\/strong>S\u00edndroma: Progn\u00f3stico favor\u00e1vel, possibilidade de regress\u00e3o espont\u00e2nea<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>Correla\u00e7\u00e3o cl\u00ednico-patol\u00f3gica<\/strong>&nbsp;\u00e9 crucial para um diagn\u00f3stico e um planeamento de tratamento corretos.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">No caso de les\u00f5es eczematosas que s\u00e3o refract\u00e1rias \u00e0 terapia, o linfoma cut\u00e2neo deve ser considerado numa fase inicial.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"BALL\"><span class=\"ez-toc-section\" id=\"B-lymphoblastisches_LymphomLeukamie_B-ALL\"><\/span><strong>Linfoma\/leucemia linfobl\u00e1stica B (B-ALL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O <strong>Linfoma\/leucemia linfobl\u00e1stica B (B-ALL)<\/strong>&nbsp;\u00e9 uma neoplasia aguda e agressiva das c\u00e9lulas precursoras das c\u00e9lulas B que pode manifestar-se clinicamente como leucemia ou linfoma.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial inclui outras neoplasias linf\u00e1ticas, em particular a&nbsp;<strong>linfoma difuso de grandes c\u00e9lulas B (DLBCL)<\/strong>, que&nbsp;<strong>Linfoma de Burkitt<\/strong>&nbsp;e&nbsp;<strong>Leucemia aguda de c\u00e9lulas T (T-ALL)<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Um diagn\u00f3stico diferenciado \u00e9 crucial, uma vez que o tratamento e o progn\u00f3stico dependem fortemente da categoriza\u00e7\u00e3o exacta.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild_und_klinisch-morphologische_Merkmale-4\"><\/span>Quadro cl\u00ednico e carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Sintomas<\/strong><br>Insufici\u00eancia da medula \u00f3ssea com anemia (fadiga, dispneia), neutropenia (infec\u00e7\u00f5es), trombocitopenia (hemorragias), sintomas B (febre, suores noturnos, perda de peso). S\u00e3o poss\u00edveis manifesta\u00e7\u00f5es extramedulares, como linfonodomegalia, hepato- e esplenomegalia, massas mediast\u00ednicas (especialmente em T-ALL) ou envolvimento do SNC (5-8% aquando do diagn\u00f3stico)<\/li>\n\n\n\n<li><strong>Citomorfologia<\/strong><br>Linfoblastos com um n\u00facleo grande, cromatina finamente distribu\u00edda, v\u00e1rios nucl\u00e9olos e pouco citoplasma. As c\u00e9lulas apresentam uma elevada atividade de prolifera\u00e7\u00e3o (\u00edndice Ki67 elevado)<\/li>\n\n\n\n<li><strong>Imunofen\u00f3tipo<\/strong><br>Positivo para&nbsp;<strong>CD19, CD20, CD22, CD79a<\/strong>,&nbsp;<strong>TdT<\/strong>&nbsp;(desoxinucleotidil transferase terminal),&nbsp;<strong>CD34<\/strong>&nbsp;(frequente),&nbsp;<strong>HLA-DR<\/strong><br>Negativo para marcadores mieloides (CD13, CD33) e marcadores de c\u00e9lulas T (CD2, CD3, CD5)<\/li>\n\n\n\n<li><strong>Marcadores gen\u00e9ticos<\/strong><br>Transloca\u00e7\u00f5es t\u00edpicas, tais como&nbsp;<strong>t(9;22)<\/strong>&nbsp;(BCR-ABL1),&nbsp;<strong>t(12;21)<\/strong>&nbsp;(ETV6-RUNX1),&nbsp;<strong>t(1;19)<\/strong>&nbsp;(E2A-PBX1),&nbsp;<strong>IGH::IL3<\/strong>,&nbsp;<strong>TCF3::PBX1<\/strong>, assim como&nbsp;<strong>BCR::ABL1-like<\/strong>&nbsp;Variantes com ativa\u00e7\u00e3o das vias de sinaliza\u00e7\u00e3o JAK\/STAT ou ABL quinase.<br><strong>Dele\u00e7\u00f5es de IKZF1<\/strong>&nbsp;s\u00e3o comuns e est\u00e3o associadas a um progn\u00f3stico desfavor\u00e1vel.<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-18\"><\/span>Diagn\u00f3stico diferencial<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Diagn\u00f3stico diferencial<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>DLBCL (linfoma difuso de grandes c\u00e9lulas B)<\/strong>O tamanho e a morfologia das c\u00e9lulas s\u00e3o semelhantes, mas&nbsp;<strong>TdT-negativo<\/strong>,&nbsp;<strong>CD10 positivo<\/strong>&nbsp;(para o tipo GCB),&nbsp;<strong>BCL2 positivo<\/strong>,&nbsp;<strong>BCL6 positivo<\/strong>,&nbsp;<strong>MYC negativo<\/strong>.  Sem leucemia ou insufici\u00eancia da medula \u00f3ssea<\/li>\n\n\n\n<li><strong>Linfoma de Burkitt<\/strong>Morfologia semelhante (blastos),&nbsp;<strong>Transloca\u00e7\u00e3o MYC<\/strong>&nbsp;(t(8;14)),&nbsp;<strong>\u00edndice Ki67 elevado (&gt;95%)<\/strong>,&nbsp;<strong>CD10 positivo<\/strong>,&nbsp;<strong>BCL2 negativo<\/strong>.  Principalmente extranodal (abd\u00f3men, SNC)<\/li>\n\n\n\n<li><strong>T-ALL<\/strong>CD3+, CD7+, TdT+, marcadores de c\u00e9lulas B em falta, frequentemente linfonodomegalia mediast\u00ednica<\/li>\n\n\n\n<li><strong>Linfomas linfobl\u00e1sticos (B-LBL)<\/strong>Clinicamente semelhante ao LLA-B, mas sem altera\u00e7\u00f5es significativas da contagem sangu\u00ednea, envolvimento linf\u00e1tico prim\u00e1rio<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostikmethoden\"><\/span><strong>M\u00e9todos de diagn\u00f3stico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Citomorfologia<\/strong>&nbsp;(sangue perif\u00e9rico, medula \u00f3ssea, biopsia de g\u00e2nglios linf\u00e1ticos).<\/li>\n\n\n\n<li><strong>Imunofenotipagem<\/strong>&nbsp;(citometria de fluxo, imunohistoqu\u00edmica).<\/li>\n\n\n\n<li><strong>Citogen\u00e9tica<\/strong>&nbsp;(cariotipagem).<\/li>\n\n\n\n<li><strong>PEIXE<\/strong>&nbsp;(para transloca\u00e7\u00f5es: t(9;22), t(12;21), t(1;19), IGH::IL3, CRLF2).<\/li>\n\n\n\n<li><strong>Gen\u00e9tica molecular (NGS)<\/strong>&nbsp;para a identifica\u00e7\u00e3o de muta\u00e7\u00f5es (por exemplo.&nbsp;&nbsp;<strong>IKZF1<\/strong>,&nbsp;<strong>PAX5<\/strong>,&nbsp;<strong>EBF1<\/strong>,&nbsp;<strong>JAK\/STAT<\/strong>,&nbsp;<strong>Via de sinaliza\u00e7\u00e3o RAS<\/strong>).<\/li>\n\n\n\n<li><strong>Exame do l\u00edquido cefalorraquidiano<\/strong>&nbsp;para suspeita do SNC.<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-21\"><\/span>Terapia<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Terapia de primeira linha<\/strong><br>Regimes de quimioterapia intensiva, por exemplo.&nbsp;<strong>Blinatumomab<\/strong>&nbsp;(anticorpos BiTE) ou&nbsp;<strong>Inotuzumab ozogamicina<\/strong>&nbsp;(conjugado anticorpo-f\u00e1rmaco) em combina\u00e7\u00e3o com quimioterapia<br>Para adultos:&nbsp;<strong>Hiper-CVAD<\/strong>&nbsp;(ciclofosfamida, vincristina, doxorrubicina, dexametasona) ou&nbsp;<strong>Blinatumomab<\/strong><\/li>\n\n\n\n<li><strong>Transplante alog\u00e9nico de c\u00e9lulas estaminais<\/strong><br>Em doentes com uma gen\u00e9tica desfavor\u00e1vel (por exemplo.&nbsp;<strong>BCR::ABL1<\/strong>,&nbsp;<strong>Dele\u00e7\u00e3o de IKZF1<\/strong>,&nbsp;<strong>contagem baixa de gl\u00f3bulos brancos<\/strong>), risco elevado ou recorr\u00eancia<\/li>\n\n\n\n<li><strong>Profilaxia do SNC<\/strong><br>Metotrexato (intratecal), terapia com corticoster\u00f3ides, frequentemente combinada com quimioterapia sist\u00e9mica<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-20\"><\/span>Previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Favor\u00e1vel<\/strong><br>T-ALL com&nbsp;<strong>t(12;21)<\/strong>,&nbsp;<strong>BCR::ABL1-negativo<\/strong>,&nbsp;<strong>Doentes idosos com baixo risco<\/strong><\/li>\n\n\n\n<li><strong>Desfavor\u00e1vel<\/strong><br><strong>BCR::ABL1-positivo<\/strong>,&nbsp;<strong>BCR::ABL1-like<\/strong>&nbsp;Variantes,&nbsp;<strong>Dele\u00e7\u00e3o de IKZF1<\/strong>,&nbsp;<strong>contagem baixa de gl\u00f3bulos brancos<\/strong>,&nbsp;<strong>Pacientes idosos<\/strong>,&nbsp;<strong>Envolvimento do SNC<\/strong><br>A taxa de sobreviv\u00eancia de 5 anos \u00e9 de cerca de&nbsp;<strong>60-70%<\/strong>&nbsp;nas crian\u00e7as, significativamente inferior nos adultos (aprox.&nbsp;&nbsp;<strong>40-50%<\/strong>), especialmente com perfis gen\u00e9ticos desfavor\u00e1veis<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Diagn\u00f3sticos modernos utilizando&nbsp;<strong>NGS e FISH<\/strong>&nbsp;permite uma classifica\u00e7\u00e3o exacta dos riscos e abordagens terap\u00eauticas personalizadas.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"TALL\"><span class=\"ez-toc-section\" id=\"T-lymphoblastisches_LymphomLeukamie_T-ALL\"><\/span><strong>Linfoma\/leucemia linfobl\u00e1stica T (T-ALL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O <strong>Leucemia linfobl\u00e1stica aguda de c\u00e9lulas T (T-ALL) e linfoma linfobl\u00e1stico de c\u00e9lulas T (T-LBL)<\/strong>&nbsp;s\u00e3o doen\u00e7as malignas das c\u00e9lulas precursoras linf\u00e1ticas caracterizadas pela prolifera\u00e7\u00e3o descontrolada de linf\u00f3citos T imaturos (linfoblastos).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A doen\u00e7a pode ocorrer principalmente na medula \u00f3ssea (leucemia) ou nos g\u00e2nglios linf\u00e1ticos e \u00f3rg\u00e3os extranodais (linfoma), sendo a distin\u00e7\u00e3o feita com base na propor\u00e7\u00e3o de blastos na medula \u00f3ssea (geralmente &gt;20-25%).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A LLA-T ocorre menos frequentemente em crian\u00e7as e adolescentes do que a LLA-B (cerca de 15 % de todos os casos de LLA), mas \u00e9 mais comum em adultos (cerca de 25 %).<br>A doen\u00e7a tem dois picos de incid\u00eancia: na inf\u00e2ncia (menos de 5 anos de idade) e na idade adulta (mais de 50 anos de idade). <\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Clinicamente, o T-ALL manifesta-se tipicamente com sintomas de insufici\u00eancia da medula \u00f3ssea (anemia, trombocitopenia, neutropenia), febre, perda de peso, suores noturnos e dores \u00f3sseas.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">As carater\u00edsticas s\u00e3o&nbsp;<strong>Hepatoesplenomegalia<\/strong>,&nbsp;<strong>Linfadenopatia<\/strong>&nbsp;e em cerca de 5-8 % dos doentes uma&nbsp;<strong>Envolvimento do SNC<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">No caso de LLA-T do tipo de c\u00e9lulas T&nbsp;<strong>massas mediastinais<\/strong>&nbsp;no t\u00f3rax que se tornam clinicamente relevantes como sintomas de press\u00e3o (por exemplo, falta de ar, tosse) ou como indica\u00e7\u00e3o para radioterapia.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisch-morphologische_Merkmale-8\"><\/span><strong>Carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Citomorfologia<\/strong><br>Os linfoblastos apresentam um elevado n\u00famero de c\u00e9lulas, n\u00facleos celulares grandes com cromatina fina e 1-3 nucl\u00e9olos. A quantidade de citoplasma \u00e9 pequena<\/li>\n\n\n\n<li><strong>Imunofenotipagem (fundamental para o diagn\u00f3stico)<\/strong><br>Os blastos expressam antig\u00e9nios de superf\u00edcie espec\u00edficos das c\u00e9lulas T, tais como&nbsp;<strong>CD2, CD3, CD5, CD7<\/strong>&nbsp;(maioritariamente muito positivos),&nbsp;<strong>CD1a<\/strong>&nbsp;(para os subtipos t\u00edmicos),&nbsp;<strong>TdT<\/strong>&nbsp;(desoxinucleotidil transferase terminal) e&nbsp;<strong>CD4\/CD8<\/strong>&nbsp;(consoante o est\u00e1dio de diferencia\u00e7\u00e3o: imaturo precoce, t\u00edmico ou maduro T-ALL)<br><strong>CD7<\/strong>&nbsp;\u00e9 positivo em mais de 90 casos de %.  A fenotipagem CD4+\/CD8- \u00e9 t\u00edpica de LLA-T imatura precoce<\/li>\n\n\n\n<li><strong>Citogen\u00e9tica e marcadores gen\u00e9ticos moleculares<\/strong><br>As aberra\u00e7\u00f5es gen\u00e9ticas mais comuns incluem&nbsp;<strong>t(14;14)(q11;q32)<\/strong>,&nbsp;<strong>inv(14)(q11q32)<\/strong>,&nbsp;<strong>t(X;14)(q11;q32)<\/strong>&nbsp;e&nbsp;<strong>del(11q)<\/strong><br>Outros marcadores de risco s\u00e3o&nbsp;<strong>Muta\u00e7\u00f5es ATM<\/strong>&nbsp;(em 60 %),&nbsp;<strong>Muta\u00e7\u00f5es TP53<\/strong>&nbsp;(para 20-30 %) e&nbsp;<strong>Dele\u00e7\u00f5es de IKZF1<\/strong><br>O&nbsp;<strong>Sequencia\u00e7\u00e3o de nova gera\u00e7\u00e3o (NGS)<\/strong>-A an\u00e1lise est\u00e1 a ser cada vez mais utilizada para identificar altera\u00e7\u00f5es gen\u00e9ticas complexas e para a avalia\u00e7\u00e3o de riscos<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-19\"><\/span><strong>Diagn\u00f3stico diferencial<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial inclui outras doen\u00e7as linfoproliferativas:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>LLA de c\u00e9lulas B\/LBL<\/strong><br>Diferencia\u00e7\u00e3o por antig\u00e9nios de c\u00e9lulas T em falta (CD3, CD7, CD2), marcadores de c\u00e9lulas B positivos (CD19, CD20, CD79a)<\/li>\n\n\n\n<li><strong>Leucemia prolinfoc\u00edtica de c\u00e9lulas T (T-PLL)<\/strong><br>Diferencia\u00e7\u00e3o por progress\u00e3o mais lenta, morfologia celular t\u00edpica (n\u00facleos grandes e cerebriformes), fen\u00f3tipo CD4+\/CD8- com&nbsp;<strong>CD26+, CD52+, TCL1A+<\/strong>, assim como&nbsp;<strong>Cari\u00f3tipo complexo<\/strong>&nbsp;e&nbsp;<strong>inv(14)<\/strong><\/li>\n\n\n\n<li><strong>Leucemia linfoc\u00edtica cr\u00f3nica (LLC)<\/strong><br>Nas LLA-T (raras), est\u00e3o ausentes os marcadores t\u00edpicos das LLA (CD5+, CD23+, CD79b-)<\/li>\n\n\n\n<li><strong>S\u00edndrome de S\u00e9zary<\/strong><br>Uma forma de linfoma cut\u00e2neo de c\u00e9lulas T com eritrodermia, prurido, alop\u00e9cia e fen\u00f3tipo CD4+\/CD8- com&nbsp;<strong>CD7-, CD26-<\/strong><\/li>\n\n\n\n<li><strong>Leucemia\/linfoma de c\u00e9lulas T do adulto (ATLL)<\/strong><br>Causado por&nbsp;<strong>HTLV-I<\/strong>, ocorre em zonas end\u00e9micas (Jap\u00e3o, Cara\u00edbas)<br>espect\u00e1culos&nbsp;<strong>CD25++<\/strong>,&nbsp;<strong>CD4+\/CD8-<\/strong>,&nbsp;<strong>CD7-<\/strong>,&nbsp;<strong>Muta\u00e7\u00f5es TP53<\/strong>&nbsp;e&nbsp;<strong>HTLV-I-DNA<\/strong>&nbsp;no sangue<\/li>\n\n\n\n<li><strong>Linfoma linfobl\u00e1stico T (T-LBL)<\/strong><br>Diferencia\u00e7\u00e3o de LLA-T por envolvimento extramedular prim\u00e1rio (por exemplo, mediastino), sem ou com baixo envolvimento da medula \u00f3ssea (&lt;20 blastos %)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostik-3\"><\/span><strong>Diagn\u00f3stico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Esfrega\u00e7o de sangue e biopsia da medula \u00f3ssea<\/strong><br>Dete\u00e7\u00e3o de linfoblastos (&gt;20 % na medula \u00f3ssea para a LLA)<\/li>\n\n\n\n<li><strong>Imunofenotipagem (citometria de fluxo)<\/strong><br>Obrigat\u00f3rio para a identifica\u00e7\u00e3o do fen\u00f3tipo das c\u00e9lulas T<\/li>\n\n\n\n<li><strong>An\u00e1lise cromoss\u00f3mica (cari\u00f3tipo)<\/strong><br>Identifica\u00e7\u00e3o de transloca\u00e7\u00f5es como a t(14;14), inv(14)<\/li>\n\n\n\n<li><strong>FISH (hibrida\u00e7\u00e3o in situ por fluoresc\u00eancia)<\/strong><br>Dete\u00e7\u00e3o r\u00e1pida de aberra\u00e7\u00f5es cr\u00edpticas (por exemplo.&nbsp;<strong>t(14;14)<\/strong>)<\/li>\n\n\n\n<li><strong>Gen\u00e9tica molecular (PCR, NGS)<\/strong><br>Dete\u00e7\u00e3o de transcri\u00e7\u00f5es de fus\u00e3o (por exemplo.&nbsp;<strong>TAL1<\/strong>,&nbsp;<strong>LYL1<\/strong>,&nbsp;<strong>HOXA<\/strong>-genes), muta\u00e7\u00f5es (<strong>TP53<\/strong>,&nbsp;<strong>ATM<\/strong>,&nbsp;<strong>IKZF1<\/strong>).<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-22\"><\/span><strong>Terapia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Terapia de indu\u00e7\u00e3o<\/strong><br>Quimioterapia intensiva com ester\u00f3ides (por exemplo, dexametasona), vincristina, ciclofosfamida, daunorubicina e metotrexato (por exemplo.&nbsp;<strong>Protocolo UKALL2003<\/strong>)<\/li>\n\n\n\n<li><strong>Consolida\u00e7\u00e3o e preserva\u00e7\u00e3o<\/strong><br>Fase de terapia intensiva com profilaxia do sistema nervoso central (por exemplo, metotrexato intratecal)<\/li>\n\n\n\n<li><strong>Transplante alog\u00e9nico de c\u00e9lulas estaminais (SCT)<\/strong><br>Indicado para o risco elevado (por exemplo.&nbsp;<strong>Muta\u00e7\u00e3o TP53<\/strong>,&nbsp;<strong>Rearranjo KMT2A<\/strong>,&nbsp;<strong>Sem remiss\u00e3o ap\u00f3s a indu\u00e7\u00e3o<\/strong>)<\/li>\n\n\n\n<li><strong>Terapia dirigida<\/strong><br>Para certos subtipos (por exemplo.&nbsp;<strong>Muta\u00e7\u00f5es activadoras de JAK-STAT<\/strong>) s\u00e3o&nbsp;<strong>Inibidores da JAK<\/strong>&nbsp;(por exemplo, ruxolitinib) est\u00e3o a ser investigados<br><strong>Blinatumomab<\/strong>&nbsp;(anticorpo BiTE) \u00e9 utilizado em casos individuais<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-21\"><\/span><strong>Previs\u00e3o<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Factores de progn\u00f3stico desfavor\u00e1veis:<br><strong>Idade &gt;50 anos<\/strong>,&nbsp;<strong>Contagem elevada de leuc\u00f3citos<\/strong>,&nbsp;<strong>Infiltra\u00e7\u00e3o da medula \u00f3ssea<\/strong>,&nbsp;<strong>Envolvimento do SNC<\/strong>,&nbsp;<strong>Muta\u00e7\u00e3o TP53<\/strong>,&nbsp;<strong>Muta\u00e7\u00e3o ATM<\/strong>,&nbsp;<strong>Rearranjo KMT2A<\/strong>,&nbsp;<strong>T-ALL com fen\u00f3tipo maduro<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Nas crian\u00e7as, a taxa de cura \u00e9 de&nbsp;<strong>85 %<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">O progn\u00f3stico \u00e9 pior para os adultos:&nbsp;<strong>50-60 %<\/strong>&nbsp;alcan\u00e7ar uma remiss\u00e3o a longo prazo<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"NK-Zell-Lymphome-2\"><\/span><strong>Linfomas de c\u00e9lulas NK<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"ENKTL-NT\"><span class=\"ez-toc-section\" id=\"Extranodales_NK-Zell-Lymphom\"><\/span><strong>Linfoma extranodal de c\u00e9lulas NK<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O <strong>Linfoma extranodal de c\u00e9lulas NK\/T de tipo nasal (ENKTL-NT)<\/strong>&nbsp;\u00e9 um <strong>tamb\u00e9m associado ao EBV<\/strong>, uma forma rara e agressiva de linfoma n\u00e3o-Hodgkin, que se caracteriza predominantemente por&nbsp;<strong>c\u00e9lulas assassinas naturais (c\u00e9lulas NK)<\/strong>&nbsp;ou c\u00e9lulas T e est\u00e1 intimamente ligada \u00e0&nbsp;<strong>Infe\u00e7\u00e3o pelo v\u00edrus Epstein-Barr (EBV)<\/strong>&nbsp;associado a&nbsp;<strong>Positividade de CD56, dete\u00e7\u00e3o de EBV e crescimento angioc\u00eantrico<\/strong>&nbsp;\u00e9 caracterizado.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Ocorre predominantemente na \u00c1sia, Am\u00e9rica Central e do Sul e afecta principalmente adultos, embora os homens sejam mais frequentemente afectados.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">&nbsp;A terapia \u00e9&nbsp;<strong>combinado<\/strong>&nbsp;(radioterapia + quimioterapia), o progn\u00f3stico permanece&nbsp;<strong>relativamente pobre<\/strong>, No entanto, a situa\u00e7\u00e3o est\u00e1 a melhorar com as novas imunoterapias.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild_und_morphologische_Merkmale\"><\/span><strong>Quadro cl\u00ednico e carater\u00edsticas morfol\u00f3gicas<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cl\u00ednica<\/strong><br>Os sintomas t\u00edpicos come\u00e7am com congest\u00e3o nasal cr\u00f3nica, hemorragias nasais e les\u00f5es ulceradas e dolorosas na cavidade nasal<br>As fases avan\u00e7adas mostram destrui\u00e7\u00e3o centrofacial, destrui\u00e7\u00e3o da base do cr\u00e2nio, necrose das narinas e do septo, e sintomas B como febre, suores noturnos e perda de peso<\/li>\n\n\n\n<li><strong>Morfol\u00f3gico<\/strong><br>Histologicamente, o linfoma caracteriza-se por&nbsp;<strong>Crescimento angioc\u00eantrico e angiodestrutivo<\/strong>&nbsp;com necrose de coagula\u00e7\u00e3o extensa<br>As c\u00e9lulas tumorais s\u00e3o de tamanho m\u00e9dio a grande, com n\u00facleos irregulares e cromatina granular. Est\u00e3o frequentemente rodeadas por um denso infiltrado de c\u00e9lulas reactivas (linf\u00f3citos, macr\u00f3fagos, granul\u00f3citos eosinof\u00edlicos)<\/li>\n\n\n\n<li><strong>Imunofen\u00f3tipo<\/strong><br><strong>CD56 positivo<\/strong>&nbsp;(id\u00eantico ao N-CAM),&nbsp;<strong>CD4 positivo<\/strong>,&nbsp;<strong>CD8 negativo<\/strong>,&nbsp;<strong>CD20 negativo<\/strong>,&nbsp;<strong>CD30 em cerca de 20% positivos<\/strong>.<br>O&nbsp;<strong>Dete\u00e7\u00e3o do ARN do EBV<\/strong>&nbsp;por meio de&nbsp;<strong>Hibrida\u00e7\u00e3o in situ EBER<\/strong>&nbsp;\u00e9 inovador<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-20\"><\/span><strong>Diagn\u00f3stico diferencial<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial inclui<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Granuloma gangraenescens nasi<\/strong>&nbsp;(designa\u00e7\u00e3o mais antiga)<br>Doen\u00e7a inflamat\u00f3ria que pode ter um aspeto cl\u00ednico e histol\u00f3gico semelhante, mas que n\u00e3o \u00e9 maligna<\/li>\n\n\n\n<li><strong>Doen\u00e7as infecciosas ou granulomatosas<\/strong>&nbsp;(por exemplo, tuberculose, leishmaniose, sarcoidose) - a diferenciar atrav\u00e9s de exames cl\u00ednicos, microbiol\u00f3gicos e histol\u00f3gicos<\/li>\n\n\n\n<li><strong>Outros linfomas de c\u00e9lulas T<\/strong>, em particular&nbsp;<strong>linfomas cut\u00e2neos de c\u00e9lulas T<\/strong>,&nbsp;<strong>linfoma angioimunobl\u00e1stico de c\u00e9lulas T<\/strong>&nbsp;ou&nbsp;<strong>Linfomas de c\u00e9lulas T associados a enteropatias<\/strong>, a diferenciar por imunofenotipagem e an\u00e1lise molecular (por exemplo, genes de receptores de c\u00e9lulas T)<\/li>\n\n\n\n<li><strong>Neoplasia associada ao EBV na infe\u00e7\u00e3o pelo VIH<\/strong>, considera\u00e7\u00e3o especial para pacientes imunocomprometidos<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial requer uma clarifica\u00e7\u00e3o histol\u00f3gica e biol\u00f3gica molecular cuidadosa<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostikmethodik-2\"><\/span><strong>Metodologia de diagn\u00f3stico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Bi\u00f3psia<\/strong>&nbsp;do tecido afetado (por exemplo, parede nasal, pele, trato gastrointestinal), base central de diagn\u00f3stico<\/li>\n\n\n\n<li><strong>Imunohistoqu\u00edmica<\/strong><br>Dete\u00e7\u00e3o de CD56, CD4, CD3, CD30, CD20 (negativo), bem como de EBV (hibrida\u00e7\u00e3o EBER)<\/li>\n\n\n\n<li><strong>M\u00e9todos de biologia molecular<\/strong><br>Dete\u00e7\u00e3o de genes clonais de receptores de c\u00e9lulas T (para a linhagem de c\u00e9lulas T), FISH para a dete\u00e7\u00e3o de altera\u00e7\u00f5es gen\u00e9ticas<\/li>\n\n\n\n<li><strong>Imagiologia<\/strong><br>TC ou RMN para avaliar a extens\u00e3o (por exemplo, infesta\u00e7\u00e3o da base do cr\u00e2nio, les\u00f5es extranodais)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-23\"><\/span><strong>Terapia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Doen\u00e7a localizada<\/strong><br><strong>Radioterapia<\/strong>&nbsp;como tratamento padr\u00e3o.&nbsp;<\/li>\n\n\n\n<li><strong>Doen\u00e7a sist\u00e9mica ou taxa de recorr\u00eancia elevada<\/strong><br><strong>Terapia combinada<\/strong>&nbsp;de&nbsp;<strong>Quimioterapia<\/strong>&nbsp;(por exemplo, regimes contendo asparaginase, como SMILE ou DA-EPOCH-R) e&nbsp;<strong>Irradia\u00e7\u00e3o<\/strong><\/li>\n\n\n\n<li><strong>Novas abordagens<\/strong><br>Para casos avan\u00e7ados&nbsp;<strong>estrat\u00e9gias imunoterap\u00eauticas<\/strong>&nbsp;(por exemplo, inibidores PD-1) e&nbsp;<strong>Terapias celulares<\/strong>&nbsp;(por exemplo, c\u00e9lulas CAR-T) est\u00e3o a ser avaliadas em ensaios cl\u00ednicos<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-22\"><\/span><strong>Previs\u00e3o<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li>A previs\u00e3o \u00e9&nbsp;<strong>desfavor\u00e1vel<\/strong>, especialmente em fases avan\u00e7adas<\/li>\n\n\n\n<li><strong>Tempo m\u00e9dio de sobreviv\u00eancia<\/strong>&nbsp;\u00e9 sobre&nbsp;<strong>15-36 meses<\/strong>, dependendo do est\u00e1dio e da resposta \u00e0 terap\u00eautica.&nbsp;<\/li>\n\n\n\n<li><strong>Positividade CD30<\/strong>&nbsp;correlaciona-se com um melhor progn\u00f3stico (tempo m\u00e9dio de sobreviv\u00eancia &gt;35 meses vs. aprox. 9,6 meses para os casos CD30-negativos)<\/li>\n\n\n\n<li><strong>Quantidade de ADN do EBV no soro<\/strong>&nbsp;pode servir como um marcador de progn\u00f3stico, valores elevados est\u00e3o associados a um pior progn\u00f3stico<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"ANKL\"><span class=\"ez-toc-section\" id=\"Agressive_NK-Zell-Leukamie_ANKL\"><\/span><strong>Leucemia agressiva de c\u00e9lulas NK<\/strong> (ANKL)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">A leucemia agressiva das c\u00e9lulas NK (ANKL) \u00e9 uma doen\u00e7a rara, altamente maligna, causada pela prolifera\u00e7\u00e3o de c\u00e9lulas assassinas naturais (c\u00e9lulas NK) e tem uma evolu\u00e7\u00e3o cl\u00ednica r\u00e1pida e agressiva. Est\u00e1 fortemente associada \u00e0&nbsp;<strong>V\u00edrus Epstein-Barr (EBV)<\/strong>&nbsp;embora tamb\u00e9m sejam conhecidos casos EBV-negativos.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A doen\u00e7a \u00e9 mais comum na \u00c1sia, nomeadamente no Jap\u00e3o e no Sudeste Asi\u00e1tico, do que na Europa ou na Am\u00e9rica do Norte.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_und_morphologisches_Bild-3\"><\/span><strong>Quadro cl\u00ednico e morfol\u00f3gico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Imagem cl\u00ednica<\/strong><br>- Progress\u00e3o r\u00e1pida e agressiva com&nbsp;<strong>Sintomas B<\/strong>&nbsp;(febre, suores noturnos, perda de peso)<br>- Frequente&nbsp;<strong>Hepatoesplenomegalia<\/strong>&nbsp;e&nbsp;<strong>Linfadenopatia<\/strong><br>- <strong>Pancitopenia<\/strong>&nbsp;no hemograma (anemia, neutropenia, trombocitopenia)<br>- Para alguns doentes<br><strong>Hipersensibilidade a picadas de insectos<\/strong>&nbsp;com incha\u00e7o e necrose pronunciados<br>- Complica\u00e7\u00f5es frequentes<br><strong>Coagula\u00e7\u00e3o intravascular disseminada (CID)<\/strong>,&nbsp;<strong>S\u00edndrome hemofagoc\u00edtica (HPS)<\/strong>, fal\u00eancia m\u00faltipla de \u00f3rg\u00e3os<br><\/li>\n\n\n\n<li><strong>Carater\u00edsticas morfol\u00f3gicas (biopsia da medula \u00f3ssea)<\/strong><br>- Infiltra\u00e7\u00e3o intersticial ou sinusoidal devido a&nbsp;<strong>C\u00e9lulas neopl\u00e1sicas de tamanho m\u00e9dio<\/strong><br>- <strong>Tipos de n\u00facleo distintos<\/strong>,&nbsp;<strong>nucl\u00e9olos proeminentes<\/strong>, necrose focal e c\u00e9lulas apopt\u00f3ticas<br>- <strong>Contagem diferencial de sangue<\/strong> - C\u00e9lulas leuc\u00e9micas at\u00edpicas com&nbsp;<strong>gr\u00e2nulos azur\u00f3filos<\/strong>&nbsp;e altera\u00e7\u00f5es at\u00edpicas essenciais<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_-methodik-6\"><\/span><strong>Diagn\u00f3stico diferencial e metodologia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico de ANKL requer uma combina\u00e7\u00e3o de exames cl\u00ednicos, morfol\u00f3gicos, imuno-histoqu\u00edmicos e de biologia molecular, de modo a diferenci\u00e1-lo de outras neoplasias malignas linf\u00e1ticas:<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnosen-2\"><\/span><strong>Diagn\u00f3sticos diferenciais<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Linfoma difuso de grandes c\u00e9lulas B (DLBCL)<\/strong><br>- Em contraste com os ANKL, os DLBCL s\u00e3o tipicamente&nbsp;<strong>CD20-positivo<\/strong>,&nbsp;<strong>CD56-negativo<\/strong>&nbsp;e&nbsp;<strong>EBV-negativo<\/strong><br>- Em contraste com os ANKL, os DLBCL mostram uma&nbsp;<strong>Previs\u00e3o mais favor\u00e1vel<\/strong>&nbsp;para terapia com R-CHOP<\/li>\n\n\n\n<li><strong>Linfomas nasais de c\u00e9lulas NK\/T (ENKTL)<\/strong><br>- \u00c0 semelhan\u00e7a dos ANKL, os ENKTL est\u00e3o associados ao EBV e mostram&nbsp;<strong>CD56-positivo, CD2-positivo, CD3-negativo<\/strong><br>- Diferencia\u00e7\u00e3o: os ENKTL afectam sobretudo&nbsp;<strong>Nariz e seios paranasais<\/strong>, enquanto a ANKL \u00e9 sist\u00e9mica<br>- <strong>Hibrida\u00e7\u00e3o in situ EBER<\/strong>&nbsp;\u00e9 positivo para ambos, mas no ANKL a maioria dos&nbsp;<strong>sist\u00e9mico<\/strong>&nbsp;verific\u00e1vel<\/li>\n\n\n\n<li><strong>Linfomas perif\u00e9ricos de c\u00e9lulas T, NOS (PTCL, NOS)<\/strong><br>- PTCL, NOS s\u00e3o maioritariamente&nbsp;<strong>CD56-negativo<\/strong>,&nbsp;<strong>CD2-positivo<\/strong>,&nbsp;<strong>Rearranjo clonal dos genes dos receptores das c\u00e9lulas T<\/strong><br>- Exposi\u00e7\u00f5es ANKL&nbsp;<strong>aus\u00eancia de genes clonais de receptores de c\u00e9lulas T<\/strong>, que se refere a&nbsp;<strong>Linhagem de c\u00e9lulas NK<\/strong>&nbsp;indica<\/li>\n\n\n\n<li><strong>S\u00edndrome hemofagoc\u00edtica (HPS)<\/strong><br>- ANKL pode ser utilizado como&nbsp;<strong>doen\u00e7a causal<\/strong>&nbsp;ocorrer para HPS<br>- Diferencia\u00e7\u00e3o<br>O HPS \u00e9 um&nbsp;<strong>S\u00edndroma<\/strong>, n\u00e3o \u00e9 uma neoplasia, ANKL \u00e9 o&nbsp;<strong>Doen\u00e7a tumoral predisponente<\/strong>&nbsp;<\/li>\n\n\n\n<li><strong>Outros linfomas associados ao EBV<\/strong>&nbsp;(por exemplo, linfoma de Hodgkin, DLBCL EBV-positivo, NOS)<br>Diferencia\u00e7\u00e3o atrav\u00e9s de&nbsp;<strong>Imunohistoqu\u00edmica<\/strong>,&nbsp;<strong>EBER-ISH<\/strong>,&nbsp;<strong>An\u00e1lise da express\u00e3o gen\u00e9tica<\/strong>&nbsp;e&nbsp;<strong>Testes de clonalidade<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O seu diagn\u00f3stico diferencial requer um&nbsp;<strong>Diagn\u00f3stico exaustivo<\/strong>, em particular&nbsp;<strong>Imunohistoqu\u00edmica<\/strong>,&nbsp;<strong>EBER-ISH<\/strong>,&nbsp;<strong>PCR para genes de receptores de c\u00e9lulas T<\/strong>&nbsp;e&nbsp;<strong>An\u00e1lises biol\u00f3gicas moleculares<\/strong>.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methodik-4\"><\/span><strong>Metodologia de diagn\u00f3stico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Imunohistoqu\u00edmica<\/strong><br>- <strong>Positivo<\/strong>CD2, CD16, CD56, CD45, CD43, TIA-1, Granzima B<br>- <strong>Negativo<\/strong>: CD3, CD4, CD5, CD7, CD8, CD57, CD20, CD30<br>- <strong>CD56-positivo<\/strong>&nbsp;\u00e9 carater\u00edstico mas n\u00e3o espec\u00edfico (tamb\u00e9m em ENKTL, DLBCL)<\/li>\n\n\n\n<li><strong>An\u00e1lises biol\u00f3gicas moleculares<\/strong><br>- <strong>Hibrida\u00e7\u00e3o in situ EBER<\/strong>&nbsp;(obrigatoriamente positivo na maioria dos casos)<br>- <strong>PCR para genes clonais de receptores de c\u00e9lulas T<\/strong>:&nbsp;<strong>Negativo<\/strong>&nbsp;- \u00e9 favor\u00e1vel \u00e0 linhagem de c\u00e9lulas NK<br>- <strong>An\u00e1lises de todo o genoma (NGS)<\/strong><br>- Muta\u00e7\u00f5es em&nbsp;<strong>Via de sinaliza\u00e7\u00e3o JAK\/STAT<\/strong>&nbsp;(JAK3, STAT3),&nbsp;<strong>TP53<\/strong>,&nbsp;<strong>Dele\u00e7\u00f5es no cromossoma 6q<\/strong><br>- Diferencia\u00e7\u00e3o de outros linfomas por&nbsp;<strong>Subtipagem molecular<\/strong><\/li>\n\n\n\n<li><strong>Imagiologia<\/strong><br>- <strong>TC\/RM<\/strong>&nbsp;para a avalia\u00e7\u00e3o de hepatoesplenomegalia, envolvimento de g\u00e2nglios linf\u00e1ticos e les\u00f5es extranodais<br>- <strong>FDG-PET\/CT<\/strong>&nbsp;para estadiamento e monitoriza\u00e7\u00e3o da terapia (n\u00e3o \u00e9 padr\u00e3o, mas \u00e9 \u00fatil em caso de complica\u00e7\u00f5es)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-24\"><\/span><strong>Terapia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Terapia de primeira linha<\/strong><br>- <strong>CHOP<\/strong>&nbsp;(ciclofosfamida, doxorrubicina, vincristina, prednisona) ou&nbsp;<strong>R-CHOP<\/strong>&nbsp;(com rituximab), mas&nbsp;<strong>Baixa efic\u00e1cia<\/strong>&nbsp;na ANKL<br>- <strong>Regimes \u00e0 base de etopos\u00eddeo<\/strong>&nbsp;(por exemplo.&nbsp;<strong>Hiper-CVAD<\/strong>) s\u00e3o utilizados mais frequentemente porque respondem melhor a tumores mais agressivos<br>- <strong>Transplante alog\u00e9nico de c\u00e9lulas estaminais (allo-SCT)<\/strong><br>\u2013 \u2013 <strong>Padr\u00e3o de ouro para pacientes adequados<\/strong>, especialmente em remiss\u00e3o<br>- Oferece o&nbsp;<strong>Melhor hip\u00f3tese de remiss\u00e3o ou cura a longo prazo<\/strong><\/li>\n\n\n\n<li><strong>Terapia de segunda linha<\/strong><br>- <strong>Terapia com c\u00e9lulas T CAR<\/strong>&nbsp;(por exemplo, contra CD19 ou CD22), em ensaios cl\u00ednicos, dados limitados para ANKL<br>- <strong>Imunoterapia com anti-EBV-CTL (transplante de c\u00e9lulas T)<\/strong>, experimental, mas prometedor<br>- <strong>Inibidores da BCL2 (venetoclax)<\/strong>, em combina\u00e7\u00e3o com outros regimes, na presen\u00e7a da express\u00e3o de BCL2<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-23\"><\/span><strong>Previs\u00e3o<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Muito desfavor\u00e1vel<\/strong> - <strong>o tempo m\u00e9dio de sobreviv\u00eancia \u00e9 inferior a 12 meses<\/strong><\/li>\n\n\n\n<li><strong>Taxa de sobreviv\u00eancia a 5 anos no \u00e2mbito do 20%<\/strong><\/li>\n\n\n\n<li><strong>Factores de progn\u00f3stico desfavor\u00e1veis<\/strong><br>- LDH elevada, sintomas B, infiltra\u00e7\u00e3o da medula \u00f3ssea, DIC, hemofagocitose<br><strong>Sem resposta \u00e0 quimioterapia padr\u00e3o<\/strong>&nbsp;(por exemplo, R-CHOP)<\/li>\n\n\n\n<li><strong>Transplante alog\u00e9nico de c\u00e9lulas estaminais<\/strong>&nbsp;\u00e9 a \u00fanica abordagem com&nbsp;<strong>efeito potencialmente curativo<\/strong><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"CNKL\"><span class=\"ez-toc-section\" id=\"Chronische_NK-Zell-Leukamie\"><\/span><br><strong>Leucemia cr\u00f3nica de c\u00e9lulas NK<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">A leucemia cr\u00f3nica das c\u00e9lulas NK, tamb\u00e9m conhecida como leucemia agressiva das c\u00e9lulas NK ou linfoma agressivo das c\u00e9lulas NK, \u00e9 uma doen\u00e7a maligna rara e altamente agressiva das c\u00e9lulas assassinas naturais (c\u00e9lulas NK).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Apresenta um perfil cl\u00ednico-morfol\u00f3gico e imunofenot\u00edpico carater\u00edstico que exige um diagn\u00f3stico diferenciado.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild_und_klinisch-morphologische_Merkmale-5\"><\/span>Quadro cl\u00ednico e carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Grupo et\u00e1rio<\/strong><br>S\u00e3o sobretudo afectados&nbsp;<strong>Adolescentes e jovens adultos<\/strong>, menos frequentemente doentes idosos<\/li>\n\n\n\n<li><strong>Apresenta\u00e7\u00e3o cl\u00ednica<\/strong><br>T\u00edpicos s\u00e3o&nbsp;<strong>Infesta\u00e7\u00e3o sist\u00e9mica<\/strong>&nbsp;com&nbsp;<strong>Hepato- e esplenomegalia<\/strong>,&nbsp;<strong>Linfadenopatia<\/strong>,&nbsp;<strong>Infiltra\u00e7\u00e3o da medula \u00f3ssea<\/strong>&nbsp;e&nbsp;<strong>Envolvimento do sangue perif\u00e9rico<\/strong><\/li>\n\n\n\n<li><strong>Morfologia<\/strong><br>No sangue perif\u00e9rico e na medula \u00f3ssea&nbsp;<strong>C\u00e9lulas linf\u00f3ides grandes e at\u00edpicas<\/strong>&nbsp;com altera\u00e7\u00f5es citoplasm\u00e1ticas granulares que podem apresentar uma elevada taxa de prolifera\u00e7\u00e3o e destrui\u00e7\u00e3o celular necrosante.<br>As c\u00e9lulas t\u00eam um&nbsp;<strong>morfologia celular pleom\u00f3rfica<\/strong>&nbsp;com deforma\u00e7\u00f5es nucleares frequentes e um n\u00facleo fortemente rico em cromatina<\/li>\n\n\n\n<li><strong>Imunofen\u00f3tipo<\/strong><br>As c\u00e9lulas tumorais expressam&nbsp;<strong>CD56<\/strong>,&nbsp;<strong>CD2<\/strong>,&nbsp;<strong>CD3\u03b5 citoplot\u00edpico<\/strong>,&nbsp;<strong>Granzima B<\/strong>,&nbsp;<strong>TIA-1<\/strong>,&nbsp;<strong>Perforin<\/strong>&nbsp;e outras mol\u00e9culas citot\u00f3xicas.  S\u00e3o elas&nbsp;<strong>CD3-, CD4-, CD8- e CD5- negativos<\/strong>, que difere das c\u00e9lulas T<br>A express\u00e3o de CD56 por si s\u00f3 n\u00e3o \u00e9 espec\u00edfica, mas deve ser interpretada no contexto de outros marcadores NK<\/li>\n\n\n\n<li><strong>Patologia molecular<\/strong><br>No&nbsp;<strong>O v\u00edrus Epstein-Barr (EBV) est\u00e1 presente de forma clonal na grande maioria dos casos<\/strong>, detet\u00e1vel por meio de&nbsp;<strong>Hibrida\u00e7\u00e3o in situ EBER<\/strong><br>Existem&nbsp;<strong>Sem rearranjos do gene TCR clonal<\/strong>, o que prova a linhagem das c\u00e9lulas NK<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_-methodik-7\"><\/span>Diagn\u00f3stico diferencial e metodologia<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico requer um&nbsp;<strong>an\u00e1lise multimodal<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Exame cl\u00ednico<\/strong><br>Diferencia\u00e7\u00e3o com inflama\u00e7\u00e3o sist\u00e9mica, infec\u00e7\u00f5es e outras doen\u00e7as hematol\u00f3gicas<\/li>\n\n\n\n<li><strong>Hemograma e biopsia da medula \u00f3ssea<\/strong><br>Dete\u00e7\u00e3o de c\u00e9lulas linf\u00f3ides at\u00edpicas no sangue perif\u00e9rico e na medula \u00f3ssea<\/li>\n\n\n\n<li><strong>Imunofenotipagem (citometria de fluxo)<\/strong><br>Confirma\u00e7\u00e3o do fen\u00f3tipo CD56+, CD2+, CD3\u03b5+, mol\u00e9culas citot\u00f3xicas+ e antig\u00e9nio negativo das c\u00e9lulas T<\/li>\n\n\n\n<li><strong>Patologia molecular<\/strong>:&nbsp;<strong>Hibrida\u00e7\u00e3o in situ EBER<\/strong>&nbsp;para a dete\u00e7\u00e3o do EBV<br><strong>PCR para rearranjos clonais de TCR<\/strong>&nbsp;(geralmente negativo)<\/li>\n\n\n\n<li><strong>Diagn\u00f3sticos diferenciais<\/strong><br>- <strong>Linfoma nasal de c\u00e9lulas NK\/T<\/strong><br>Fen\u00f3tipo semelhante, mas&nbsp;<strong>Localiza\u00e7\u00e3o local (nariz, nasofaringe)<\/strong><br>Forte crescimento angioc\u00eantrico<br><strong>tamb\u00e9m EBV+<\/strong><br>- <strong>Linfomas agressivos de c\u00e9lulas B<\/strong>&nbsp;(por exemplo, DLBCL)<br>CD20+, CD5-, CD10+<br><strong>sem CD56+<\/strong>;&nbsp;<strong>sem EBV+<\/strong><br>- <strong>Linfomas de c\u00e9lulas T<\/strong><br>CD3+, CD4+ ou CD8+<br><strong>Rearranjo clonal do TCR<\/strong>;&nbsp;<strong>CD56- ou fraco<\/strong><br>- <strong>Linfadenopatias reactivas<\/strong>&nbsp;(por exemplo, linfadenite de Kikuchi):<br>Infiltrados focais, apoptose em massa,&nbsp;<strong>jovens mulheres asi\u00e1ticas<\/strong><br><strong>sem EBV+<\/strong><br><strong>Sem infesta\u00e7\u00e3o sist\u00e9mica<\/strong><br>- <strong>Leucemias miel\u00f3ides<\/strong><br><strong>CD3-<\/strong>,&nbsp;<strong>CD13\/CD33+<\/strong>,&nbsp;<strong>sem CD56+<\/strong><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-25\"><\/span>Terapia<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Terapia padr\u00e3o<\/strong><br><strong>Quimioterapia intensiva<\/strong>&nbsp;(por exemplo, CHOP, Hyper-CVAD) em combina\u00e7\u00e3o com&nbsp;<strong>anticorpos anti-CD52 (alemtuzumab)<\/strong>&nbsp;ou&nbsp;<strong>anticorpos anti-CD25 (denileukin diftitox)<\/strong><\/li>\n\n\n\n<li><strong>Terapias direcionadas<\/strong><br><strong>Inibidores da BTK (por exemplo, ibrutinib)<\/strong>&nbsp;e&nbsp;<strong>Inibidores da PI3K (por exemplo, idelalisib)<\/strong>&nbsp;s\u00e3o eficazes em casos individuais, especialmente em tumores EBV-positivos<\/li>\n\n\n\n<li><strong>Transplante alog\u00e9nico de c\u00e9lulas estaminais (SCT)<\/strong><br><strong>A \u00fanica terapia potencialmente curativa<\/strong>, especialmente em doentes com bom estado geral de sa\u00fade e com um dador adequado.<br>Indicado para&nbsp;<strong>Falha do tratamento de primeira linha ou recidiva<\/strong><\/li>\n\n\n\n<li><strong>Imunoterapia<\/strong><br><strong>Terapias celulares baseadas em c\u00e9lulas NK<\/strong>&nbsp;e&nbsp;<strong>C\u00e9lulas CAR-NK<\/strong>&nbsp;s\u00e3o avaliados em estudos cl\u00ednicos<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-24\"><\/span>Previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Muito desfavor\u00e1vel<\/strong><br>O&nbsp;<strong>A taxa de sobreviv\u00eancia a 5 anos \u00e9 inferior a 20 %<\/strong>, especialmente numa fase avan\u00e7ada.&nbsp;<\/li>\n\n\n\n<li><strong>Factores de progn\u00f3stico desfavor\u00e1vel<\/strong><br>- <strong>Infesta\u00e7\u00e3o sist\u00e9mica<\/strong><br>- <strong>Envolvimento da medula \u00f3ssea<\/strong><br>- <strong>Massa tumoral elevada<\/strong><br>- <strong>Positividade ao EBV<\/strong><br>- <strong>Elevada taxa de prolifera\u00e7\u00e3o<\/strong><\/li>\n\n\n\n<li><strong>Factores de progn\u00f3stico favor\u00e1veis<\/strong><br>- <strong>Diagn\u00f3stico precoce<\/strong><br>- <strong>Bom estado geral<\/strong><br>. <strong>Rea\u00e7\u00e3o \u00e0 quimioterapia<\/strong><br>- <strong>Sucesso do SCT alog\u00e9nico<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico e a terapia requerem um&nbsp;<strong>coopera\u00e7\u00e3o multidisciplinar<\/strong>&nbsp;entre hematologistas, oncologistas, patologistas e laborat\u00f3rios de biologia molecular.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Hodgkin-Lymphom_%E2%80%93_Verwandte_Erkrankungen-2\"><\/span><strong><strong>Linfoma de Hodgkin<\/strong> - Doen\u00e7as relacionadas<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"NLPHL\"><span class=\"ez-toc-section\" id=\"Nodulares_lymphozytenpradominantes_Hodgkin-Lymphom_NLPHL\"><\/span><strong>Linfoma de Hodgkin nodular com predomin\u00e2ncia de linf\u00f3citos (NLPHL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O <strong>Linfoma de Hodgkin nodular com predomin\u00e2ncia de linf\u00f3citos (NLPHL)<\/strong>&nbsp;\u00e9 um subtipo raro de linfoma de Hodgkin, que pode causar cerca de&nbsp;<strong>5-10 % de todos os casos de linfoma de Hodgkin<\/strong>&nbsp;faz a diferen\u00e7a.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Caracteriza-se por uma&nbsp;<strong>Previs\u00e3o favor\u00e1vel<\/strong>, a&nbsp;<strong>Idade t\u00edpica de manifesta\u00e7\u00e3o antes dos 40 anos<\/strong>&nbsp;e um&nbsp;<strong>Preval\u00eancia masculina de 3:1<\/strong>&nbsp;de.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_und_morphologisches_Bild-4\"><\/span><strong>Quadro cl\u00ednico e morfol\u00f3gico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Carater\u00edsticas cl\u00ednicas<\/strong><br>- Frequentemente&nbsp;<strong>Doen\u00e7a limitada aos g\u00e2nglios linf\u00e1ticos perif\u00e9ricos<\/strong>&nbsp;(pesco\u00e7o, axila, regi\u00e3o da virilha)<br>- <strong>Raramente sintomas B<\/strong>&nbsp;(febre, suores noturnos, perda de peso)<br>- <strong>Envolvimento do mediastino raro<\/strong>, sem propaga\u00e7\u00e3o espacialmente cont\u00ednua<br>- <strong>Mais de 80 % de casos de est\u00e1dio I ou II<\/strong><br>- O envolvimento extranodal (ba\u00e7o, f\u00edgado, medula \u00f3ssea, pulm\u00f5es) s\u00f3 ocorre em&nbsp;<strong>10-15 % (ba\u00e7o), &lt;5 % (f\u00edgado, medula \u00f3ssea, pulm\u00e3o)<\/strong>&nbsp;sobre<\/li>\n\n\n\n<li><strong>Carater\u00edsticas morfol\u00f3gicas<\/strong><br>- <strong>Sem c\u00e9lulas t\u00edpicas de Hodgkin e Reed-Sternberg (HRS)<\/strong><br>- <strong>C\u00e9lulas com predomin\u00e2ncia de linf\u00f3citos malignos (LP)<\/strong>&nbsp;- c\u00e9lulas B monoclonais do centro germinal<br>- <strong>CD20-positivo<\/strong>,&nbsp;<strong>CD15-negativo<\/strong>,&nbsp;<strong>CD30-negativo<\/strong>&nbsp;(diferenciado do cl\u00e1ssico HL)<br>- <strong>Formas de crescimento t\u00edpicas<\/strong><br>\u2013 \u2013 <strong>Forma nodular (nodular) (padr\u00e3o A)<\/strong> - Previs\u00e3o mais favor\u00e1vel<br>- <strong>- Forma difusa (at\u00edpica) (padr\u00e3o C, E)<\/strong> - Mais frequentemente em fase avan\u00e7ada, maior taxa de recorr\u00eancia<br>- <strong>Angiog\u00e9nese<\/strong> - Baixa densidade de vasos (MVD), distribui\u00e7\u00e3o difusa dos vasos<br>difere do cl\u00e1ssico HL e AITL<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_-methodik-8\"><\/span><strong>Diagn\u00f3stico diferencial e metodologia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial \u00e9 crucial, uma vez que o NLPHL se sobrep\u00f5e morfol\u00f3gica e imunofenot\u00edpicamente a outros linfomas:<\/p>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><tbody><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Diagn\u00f3stico diferencial<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Carater\u00edsticas principais<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Carater\u00edsticas distintivas<\/strong><\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>LH cl\u00e1ssico rico em linf\u00f3citos (cHL)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">C\u00e9lulas HRS, CD30+\/CD15+, CD20-<\/td><td class=\"has-text-align-left\" data-align=\"left\">As c\u00e9lulas LP no NLPHL s\u00e3o CD20+ e CD30-<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Transforma\u00e7\u00e3o progressiva dos centros germinais (PTC)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Prolifera\u00e7\u00e3o do centro germinal, c\u00e9lulas B CD20+<\/td><td class=\"has-text-align-left\" data-align=\"left\">Sem destrui\u00e7\u00e3o estrutural, sem c\u00e9lulas LP; a NLPHL apresenta estruturas nodulares carater\u00edsticas<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Linfoma de grandes c\u00e9lulas B rico em c\u00e9lulas T\/histi\u00f3citos (THRLBCL)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Crescimento agressivo, contagem elevada de c\u00e9lulas T\/histi\u00f3citos<\/td><td class=\"has-text-align-left\" data-align=\"left\">Morfologia semelhante \u00e0 do NLPHL difuso;&nbsp;<strong>Diferencia\u00e7\u00e3o apenas por imunofen\u00f3tipo (c\u00e9lulas B CD20+) e exame molecular (rearranjo clonal de c\u00e9lulas B)<\/strong><\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Linfoma folicular (FL)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">CD10+, BCL2+, BCL6+<\/td><td class=\"has-text-align-left\" data-align=\"left\">Sem c\u00e9lulas LP;&nbsp;<strong>sem c\u00e9lulas LP CD20+<\/strong>, mas prolifera\u00e7\u00e3o uniforme de c\u00e9lulas B<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Linfoma angioimunobl\u00e1stico de c\u00e9lulas T (AITL)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">C\u00e9lulas T CD4+, altera\u00e7\u00f5es do VHE, c\u00e9lulas T CD10<\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>CD20- em c\u00e9lulas T<\/strong>,&nbsp;<strong>rearranjo clo-nal das c\u00e9lulas T<\/strong>; em contraste com a LNPHL, que tem c\u00e9lulas B clonais<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Linfoma folicular de c\u00e9lulas T (FTCL)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Baseado em c\u00e9lulas T, CD4+<\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>rearranjo clo-nal das c\u00e9lulas T<\/strong>,&nbsp;<strong>sem linhagem de c\u00e9lulas B<\/strong><\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostik-4\"><\/span>Diagn\u00f3stico<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Biopsia de um g\u00e2nglio linf\u00e1tico<\/strong><\/li>\n\n\n\n<li><strong>Imunohistoqu\u00edmica<\/strong><br>CD20+, CD15-, CD30-, CD45+, BCL2+ (em c\u00e9lulas LP)<\/li>\n\n\n\n<li><strong>Biologia molecular<\/strong><br>Dete\u00e7\u00e3o de rearranjos clonais de c\u00e9lulas B (genes Ig)<\/li>\n\n\n\n<li><strong>Bi\u00f3psia para dete\u00e7\u00e3o de recidiva<\/strong><br><strong>Obrigat\u00f3rio<\/strong>, como&nbsp;<strong>at\u00e9 10 % dos doentes transformam-se num linfoma agressivo de c\u00e9lulas B (por exemplo, DLBCL)<\/strong>&nbsp;experi\u00eancia<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-26\"><\/span><strong>Terapia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Fase inicial (IA sem factores de risco)<\/strong><br>- <strong>Irradia\u00e7\u00e3o da zona afetada (IFRT)<\/strong>&nbsp;com 30-36 Gy<br>- <strong>Rituximab isolado<\/strong>&nbsp;(anti-CD20) como uma op\u00e7\u00e3o alternativa, sem radia\u00e7\u00e3o, em estudos<\/li>\n\n\n\n<li><strong>Fase inicial (n\u00e3o IA ou com factores de risco)<\/strong><br>- <strong>Terapia an\u00e1loga \u00e0 cl\u00e1ssica HL<\/strong>Quimioterapia (por ex.&nbsp;<strong>ABVD<\/strong>-protocolo)<br>- <strong>Protocolos de LNH de c\u00e9lulas B<\/strong>&nbsp;(por exemplo.&nbsp;<strong>R-CHOP<\/strong>) tamb\u00e9m pode ser eficaz<\/li>\n\n\n\n<li><strong>Recorr\u00eancia<\/strong><br>- <strong>Rituximab<\/strong>&nbsp;(anti-CD20) \u00e9&nbsp;<strong>Eficaz para NLPHL recorrente<\/strong><br>- <strong>Quimioterapia de alta dose + transplante aut\u00f3logo de c\u00e9lulas estaminais<\/strong>&nbsp;apenas para&nbsp;<strong>poucos pacientes<\/strong>&nbsp;necess\u00e1rio<br>- <strong>Terapias de recupera\u00e7\u00e3o<\/strong>&nbsp;como o ICE ou de acordo com os protocolos da cHL<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-25\"><\/span><strong>Previs\u00e3o<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Muito favor\u00e1vel<\/strong><br>- <strong>Taxa de sobreviv\u00eancia a 10 anos &gt;90 %<\/strong>&nbsp;(fase limitada)<br>- <strong>O tratamento de primeira linha conduz \u00e0 remiss\u00e3o em 90-100 %<\/strong><br>- <strong>Recorr\u00eancias em 10-15 %<\/strong>, principalmente&nbsp;<strong>3-6 anos ap\u00f3s o diagn\u00f3stico<\/strong><\/li>\n\n\n\n<li><strong>Consequ\u00eancias a longo prazo<\/strong><br>- <strong>Doen\u00e7as malignas secund\u00e1rias<\/strong>&nbsp;(por exemplo, linfoma difuso de grandes c\u00e9lulas B -&nbsp;<strong>25 % Risco ap\u00f3s 20 anos<\/strong>)<br>- Carcinomas (pulm\u00e3o, mama, trato gastrointestinal) - frequentemente em regi\u00f5es tratadas com radioterapia<\/li>\n\n\n\n<li><strong>Controlo a longo prazo<\/strong>&nbsp;necess\u00e1rio<br>- Dete\u00e7\u00e3o de tumores malignos secund\u00e1rios<br>- Rastreio de doen\u00e7as cardiopulmonares (causadas pela radioterapia)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"EBV-positives_diffuses_groszelliges_B-Zell-Lymphom_PTLD\"><\/span>Linfoma difuso de grandes c\u00e9lulas B (PTLD) EBV-positivo<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O linfoma difuso de grandes c\u00e9lulas B EBV-positivo (EBV+ DLBCL) no contexto de uma doen\u00e7a linfoproliferativa p\u00f3s-transplante (PTLD) \u00e9 uma complica\u00e7\u00e3o rara, mas potencialmente fatal, ap\u00f3s o transplante de \u00f3rg\u00e3os ou de c\u00e9lulas estaminais.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Desenvolve-se normalmente em doentes com uma resposta imunit\u00e1ria imunossuprimida que n\u00e3o conseguem controlar as c\u00e9lulas B infectadas pelo v\u00edrus Epstein-Barr (EBV).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A incid\u00eancia \u00e9 maior nos primeiros anos ap\u00f3s o transplante, embora possa ocorrer um segundo pico de incid\u00eancia cinco a dez anos mais tarde.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_und_morphologisches_Bild-5\"><\/span>Quadro cl\u00ednico e morfol\u00f3gico<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Imagem cl\u00ednica<\/strong><br>A doen\u00e7a manifesta-se frequentemente&nbsp;<strong>extranodal<\/strong>&nbsp;(por exemplo, no trato gastrointestinal, pulm\u00f5es, pele, SNC), mas tamb\u00e9m pode ocorrer nodalmente<br>Os sintomas s\u00e3o inespec\u00edficos e incluem febre, suores noturnos, perda de peso (sintomas B) e disfun\u00e7\u00e3o org\u00e2nica, dependendo da localiza\u00e7\u00e3o<br>\u00c9 poss\u00edvel o envolvimento sist\u00e9mico, especialmente na forma cut\u00e2nea prim\u00e1ria<\/li>\n\n\n\n<li><strong>Carater\u00edsticas morfol\u00f3gicas<\/strong><br>- <strong>Infiltrado linfoc\u00edtico difuso e polim\u00f3rfico<\/strong>&nbsp;com blastos de c\u00e9lulas B grandes e at\u00edpicos<br>- Frequente&nbsp;<strong>C\u00e9lulas tipo Hodgkin e Reed-Sternberg<\/strong>&nbsp;(tipo HRS), necrose e ulcera\u00e7\u00e3o<br>- <strong>Positividade CD30<\/strong>&nbsp;em cerca de 10-20 % dos casos,&nbsp;<strong>CD138-negativo<\/strong>&nbsp;(diferencia-se da neoplasia de c\u00e9lulas plasm\u00e1ticas)<br>- <strong>Lat\u00eancia do EBV tipo III<\/strong>&nbsp;com express\u00e3o de EBNA-2, LMP1 e LMP2 - t\u00edpico de PTLD<br>- <strong>Imunohistoqu\u00edmica<\/strong><br>Positivo para&nbsp;<strong>CD20, CD79a, PAX5, MUM1<\/strong><br>negativo para CD5, CD10 (em contraste com GCB-DLBCL)<br>- <strong>\u00cdndice Ki67<\/strong><br>Elevada (&gt;90 %), indicando uma prolifera\u00e7\u00e3o r\u00e1pida<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-21\"><\/span>Diagn\u00f3stico diferencial<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial inclui<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>DLBCL negativo para EBV<\/strong><br>principalmente em adultos mais velhos, sem imunossupress\u00e3o<\/li>\n\n\n\n<li><strong>DLBCL cut\u00e2neo prim\u00e1rio (PCDLBCL)<\/strong><br>Localizada na pele, raramente sist\u00e9mica<\/li>\n\n\n\n<li><strong>\u00dalcera mucocut\u00e2nea EBV-positiva (EBVMCU)<\/strong><br>Curso auto-limitado, boa taxa de resposta a medidas conservadoras, sem crescimento sist\u00e9mico<\/li>\n\n\n\n<li><strong>Linfoma cut\u00e2neo prim\u00e1rio intravascular de grandes c\u00e9lulas B (PCIVLBL)<\/strong><br>Infiltrados intra e perivasculares, elevada morbilidade devido a trombose<\/li>\n\n\n\n<li><strong>Outras formas de PTLD<\/strong><br>- <strong>PTLD monom\u00f3rfica<\/strong>&nbsp;(EBV-negativo)<br>Mais frequente, monoclonal, menos reativo \u00e0 redu\u00e7\u00e3o da imunossupress\u00e3o<br>- <strong>PTLD policlonal<\/strong><br>Autolimitada, respondendo frequentemente \u00e0 redu\u00e7\u00e3o da imunossupress\u00e3o<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostik-5\"><\/span>Diagn\u00f3stico<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Histologia<\/strong><br>Bi\u00f3psia de um g\u00e2nglio linf\u00e1tico ou de um \u00f3rg\u00e3o<\/li>\n\n\n\n<li><strong>Imunohistoqu\u00edmica<\/strong><br>CD20, CD79a, MUM1, CD30, CD138<\/li>\n\n\n\n<li><strong>Dete\u00e7\u00e3o do EBV<\/strong><br><strong>Hibrida\u00e7\u00e3o in situ (ISH)<\/strong>&nbsp;para EBV-miRNA (EBER-ISH) -&nbsp;<strong>Obrigat\u00f3rio para confirma\u00e7\u00e3o<\/strong>.&nbsp;<\/li>\n\n\n\n<li><strong>PEIXE<\/strong><br>Exclus\u00e3o de rearranjos MYC\/BCL2\/BCL6 (por exemplo, para DLBCL\/HGBL-MYC\/BCL2)<\/li>\n\n\n\n<li><strong>Gen\u00e9tica molecular<\/strong><br>PCR para o ADN do EBV no soro ou no tecido (quantifica\u00e7\u00e3o para controlo)<\/li>\n\n\n\n<li><strong>Imagiologia<\/strong><br><strong>PET-CT<\/strong>&nbsp;para estadiamento e planeamento do tratamento<\/li>\n\n\n\n<li><strong>Bi\u00f3psia da medula \u00f3ssea<\/strong><br>Se houver suspeita de envolvimento sist\u00e9mico<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-27\"><\/span>Terapia<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Primeira linha<\/strong><br>- <strong>Redu\u00e7\u00e3o da imunossupress\u00e3o<\/strong>&nbsp;(com fun\u00e7\u00f5es org\u00e2nicas est\u00e1veis)<br>- <strong>Rituximab<\/strong>&nbsp;(anticorpo anti-CD20) -&nbsp;<strong>Eficaz para EBV+ PTLD<\/strong>, muitas vezes isoladamente ou em combina\u00e7\u00e3o<br>- Numa fase avan\u00e7ada:&nbsp;<strong>R-CHOP<\/strong>&nbsp;(rituximab, ciclofosfamida, doxorrubicina, vincristina, prednisona)<\/li>\n\n\n\n<li><strong>Segunda linha<\/strong><br>- <strong>Terapia com c\u00e9lulas T CAR<\/strong>&nbsp;(por exemplo, tisagenlecleucel, axicabtagene-ciloleucel) em caso de reca\u00edda ou refractariedade<br>- <strong>Prepara\u00e7\u00f5es de c\u00e9lulas T espec\u00edficas do EBV<\/strong>&nbsp;(em centros especializados)<br>- <strong>Anticorpos biespec\u00edficos<\/strong>&nbsp;(por exemplo, epcoritamab, glofitamab)<\/li>\n\n\n\n<li><strong>Quimioterapia de alta dose com transplante aut\u00f3logo de c\u00e9lulas estaminais<\/strong><br>Em doentes selecionados com recorr\u00eancias precoces<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-26\"><\/span>Previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Favor\u00e1vel<\/strong>&nbsp;com diagn\u00f3stico e terapia precoces<\/li>\n\n\n\n<li><strong>Factores desfavor\u00e1veis<\/strong><br>Idade &gt;60 anos, est\u00e1dio avan\u00e7ado (III\/IV), m\u00faltiplas localiza\u00e7\u00f5es extranodais<br><strong>LDH mais elevada<\/strong>,&nbsp;<strong>Taxa de n\u00e3o resposta \u00e0 redu\u00e7\u00e3o da imunossupress\u00e3o<\/strong><\/li>\n\n\n\n<li><strong>Sobreviv\u00eancia mediana<\/strong><br>Ap\u00f3s a terap\u00eautica com rituximab, o tempo m\u00e9dio de sobreviv\u00eancia \u00e9 de aproximadamente&nbsp;<strong>8,7 meses<\/strong>, com melhorias significativas atrav\u00e9s de terapias modernas<\/li>\n\n\n\n<li><strong>Progn\u00f3stico da PTLD EBV+<\/strong><br>geralmente melhor do que na PTLD EBV-negativa, especialmente em resposta \u00e0 redu\u00e7\u00e3o da imunossupress\u00e3o e ao rituximab<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O reconhecimento e o tratamento precoce s\u00e3o cruciais. Um&nbsp;<strong>Confer\u00eancia interdisciplinar sobre tumores<\/strong>&nbsp;\u00e9 recomendado, especialmente para casos complexos.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"IEG_MALT\"><span class=\"ez-toc-section\" id=\"Immunproliferative_Erkrankungen_Grenzfalle-2\"><\/span><strong>Doen\u00e7as imunoproliferativas e casos-limite<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"IEG_MALT\"><span class=\"ez-toc-section\" id=\"MALT-Lymphome\"><\/span><strong>Linfomas MALT<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>Linfoma MALT (linfoma do tecido linfoide associado \u00e0 mucosa)<\/strong>&nbsp;\u00e9 uma forma rara de linfoma n\u00e3o-Hodgkin maligno que tem origem nas c\u00e9lulas B e que se desenvolve normalmente nas membranas mucosas, especialmente no est\u00f4mago, nos pulm\u00f5es, nas gl\u00e2ndulas lacrimais, na gl\u00e2ndula tiroide ou nas gl\u00e2ndulas salivares.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u00c9 um&nbsp;<strong>indolente (evolu\u00e7\u00e3o lenta)<\/strong>&nbsp;O linfoma, que \u00e9 cerca de&nbsp;<strong>5 % de linfomas n\u00e3o-Hodgkin diagnosticados anualmente<\/strong>&nbsp;ocorre.  Uma etiologia decisiva \u00e9 a&nbsp;<strong>Estimula\u00e7\u00e3o imunit\u00e1ria cr\u00f3nica<\/strong>&nbsp;devido a infec\u00e7\u00f5es (por exemplo.&nbsp;<em>Helicobacter pylori<\/em>&nbsp;no est\u00f4mago) ou doen\u00e7as auto-imunes (por exemplo, s\u00edndrome de Sj\u00f6gren, tiroidite de Hashimoto).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Em contrapartida, o&nbsp;<strong>doen\u00e7a linfoproliferativa p\u00f3s-transplante (PTLD)<\/strong>&nbsp;ap\u00f3s transplante de \u00f3rg\u00e3os s\u00f3lidos ou de c\u00e9lulas estaminais alog\u00e9nicas e est\u00e1 intimamente associada a uma&nbsp;<strong>Infe\u00e7\u00e3o pelo v\u00edrus Epstein-Barr (EBV)<\/strong>&nbsp;ligado.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A PTLD ocorre com&nbsp;<strong>0,5-12 %<\/strong>&nbsp;de doentes transplantados e apresenta um espetro que vai desde les\u00f5es precoces a linfomas monom\u00f3rficos agressivos.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild_und_morphologische_Merkmale-2\"><\/span><strong>Quadro cl\u00ednico e carater\u00edsticas morfol\u00f3gicas<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Linfoma MALT<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Imagem cl\u00ednica<\/strong><br>Os sintomas s\u00e3o frequentemente inespec\u00edficos:&nbsp;<strong>Fadiga, febre, perda de peso, n\u00e1useas, anemia<\/strong><br>A infesta\u00e7\u00e3o localizada provoca sintomas org\u00e2nicos:&nbsp;<strong>Dor abdominal superior, refluxo, hemorragia no est\u00f4mago<\/strong>,&nbsp;<strong>Dist\u00farbios visuais com envolvimento da gl\u00e2ndula lacrimal<\/strong>,&nbsp;<strong>Infec\u00e7\u00f5es do trato respirat\u00f3rio com envolvimento dos pulm\u00f5es<\/strong><br>Os sintomas B (febre, suores noturnos, perda de peso) s\u00e3o raros<br><strong>Sem linfadenopatia<\/strong>&nbsp;\u00e9 t\u00edpico<\/li>\n\n\n\n<li><strong>Morfologia<\/strong><br>Histologicamente, o linfoma MALT apresenta uma&nbsp;<strong>infiltrado polim\u00f3rfico de pequenas c\u00e9lulas<\/strong>&nbsp;com fol\u00edculos reactivos que colonizam a zona marginal e a regi\u00e3o interfolicular<br>As c\u00e9lulas B neopl\u00e1sicas s\u00e3o&nbsp;<strong>CD20+, CD19+, CD22+<\/strong>, mas&nbsp;<strong>CD5-, CD10-, CD23-<\/strong><br>Transloca\u00e7\u00f5es frequentes, tais como&nbsp;<strong>t(11;18)(q21;q21)<\/strong>&nbsp;(fus\u00e3o BIRC3-MALT1) s\u00e3o relevantes em termos de progn\u00f3stico<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Doen\u00e7a linfoproliferativa p\u00f3s-transplante (PTLD)<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Imagem cl\u00ednica<\/strong><br>PTLD pode&nbsp;<strong>cedo<\/strong>&nbsp;(ap\u00f3s 3-6 meses) ou&nbsp;<strong>tardio<\/strong>&nbsp;(ap\u00f3s v\u00e1rios anos) ocorrem<br>Os sintomas dependem da infesta\u00e7\u00e3o:&nbsp;<strong>Aumento dos g\u00e2nglios linf\u00e1ticos, hepatoesplenomegalia, fal\u00eancia de \u00f3rg\u00e3os<\/strong>&nbsp;(por exemplo, insufici\u00eancia renal ap\u00f3s transplante de rim)<br><strong>EBV-positivo<\/strong>&nbsp;em mais de 90 % das les\u00f5es iniciais, mas frequentemente&nbsp;<strong>EBV-negativo<\/strong>&nbsp;para linfomas monom\u00f3rficos<\/li>\n\n\n\n<li><strong>Morfologia<\/strong><br>O PTLD apresenta um espetro:&nbsp;<strong>les\u00f5es precoces<\/strong>&nbsp;(policlonal, EBV+),&nbsp;<strong>PTLD polim\u00f3rfica<\/strong>&nbsp;(oligoclonal, EBV\u00b1),&nbsp;<strong>PTLD monom\u00f3rfica<\/strong>&nbsp;(monoclonal, frequentemente EBV-)<br>Histologicamente, assemelha-se frequentemente a um&nbsp;<strong>linfoma difuso de grandes c\u00e9lulas B (DLBCL)<\/strong><br>CD20+ e CD79a+; frequentemente&nbsp;<strong>CD30+<\/strong>,&nbsp;<strong>CD5-<\/strong><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_Diagnostik\"><\/span><strong>Diagn\u00f3stico diferencial e diagn\u00f3stico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Diagn\u00f3sticos diferenciais para Linfoma MALT<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Linfoprolifera\u00e7\u00f5es reactivas (por exemplo, no caso de&nbsp;<em>H. pylori<\/em>-gastrite)<\/li>\n\n\n\n<li>Outros linfomas n\u00e3o-Hodgkin (DLBCL, linfoma folicular)<\/li>\n\n\n\n<li>Infec\u00e7\u00f5es (por exemplo.&nbsp;<em>H. pylori<\/em>,&nbsp;<em>Chlamydia psittaci<\/em>)<\/li>\n\n\n\n<li>Doen\u00e7as auto-imunes (por exemplo, s\u00edndroma de Sj\u00f6gren, l\u00fapus)&nbsp;<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Diagn\u00f3sticos diferenciais para PTLD<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Linfadenopatia reactiva<\/li>\n\n\n\n<li>Infec\u00e7\u00f5es cr\u00f3nicas (por exemplo, infe\u00e7\u00e3o por EBV)<\/li>\n\n\n\n<li>Outros linfomas (por exemplo, DLBCL, linfoma de Hodgkin)<\/li>\n\n\n\n<li>Rejei\u00e7\u00e3o de \u00f3rg\u00e3os<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Metodologia de diagn\u00f3stico<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Bi\u00f3psia<\/strong>&nbsp;a localiza\u00e7\u00e3o afetada (padr\u00e3o de ouro)<\/li>\n\n\n\n<li><strong>Histologia, imunofenotipagem<\/strong><br>CD20, CD79a, CD5, CD10, CD23<\/li>\n\n\n\n<li><strong>An\u00e1lise PCR do rearranjo IgH<\/strong><br>para a an\u00e1lise de clonalidade<\/li>\n\n\n\n<li><strong>FISH\/Gen\u00e9tica<\/strong><br>sobre a obriga\u00e7\u00e3o de detetar transloca\u00e7\u00f5es (t(11;18), t(14;18))<\/li>\n\n\n\n<li><strong>Imagiologia<\/strong><br>(TC, MRT, PET-CT) para o estadiamento<\/li>\n\n\n\n<li><strong>Pun\u00e7\u00e3o da medula \u00f3ssea<\/strong><br>para excluir o envolvimento da medula \u00f3ssea<\/li>\n\n\n\n<li><strong>PCR do ADN do EBV no soro<\/strong><br>para o diagn\u00f3stico e monitoriza\u00e7\u00e3o de PTLD&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-28\"><\/span><strong>Terapia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"MALT-Lymphom\"><\/span><strong>Linfoma MALT<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Linfoma g\u00e1strico positivo para H. pylori<\/strong>:&nbsp;<strong>Terapia antibi\u00f3tica<\/strong>&nbsp;(erradica\u00e7\u00e3o) \u2192 frequentemente&nbsp;<strong>Regress\u00e3o<\/strong>&nbsp;de linfoma<\/li>\n\n\n\n<li><strong>Linfoma g\u00e1strico negativo para H. pylori<\/strong>&nbsp;ou&nbsp;<strong>Linfoma MALT n\u00e3o g\u00e1strico<\/strong><br>- <strong>Radioterapia<\/strong>&nbsp;(por exemplo, para o linfoma da conjuntiva)<br>- <strong>Quimioterapia<\/strong>Clorambucil, ciclofosfamida, fludarabina<br>- <strong>Rituximab<\/strong>&nbsp;(anticorpo CD20) para casos avan\u00e7ados<\/li>\n\n\n\n<li><strong>Curso indolente<\/strong>&nbsp;\u2192 Tratamento frequente&nbsp;<strong>n\u00e3o \u00e9 necess\u00e1rio<\/strong>, se assintom\u00e1tico (\u201eObservar\u201c)&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Posttransplantationale_lymphoproliferative_Storung_PTLD\"><\/span><strong>Doen\u00e7a linfoproliferativa p\u00f3s-transplante (PTLD)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Primeira linha<\/strong><br><strong>Redu\u00e7\u00e3o da imunossupress\u00e3o<\/strong>&nbsp;(Terapia de base)<\/li>\n\n\n\n<li><strong>Anticorpo monoclonal<\/strong><br><strong>Rituximab<\/strong>&nbsp;(CD20) - isoladamente ou em combina\u00e7\u00e3o<\/li>\n\n\n\n<li><strong>Quimioterapia<\/strong><br>para progress\u00e3o avan\u00e7ada ou agressiva (por exemplo, CHOP)<\/li>\n\n\n\n<li><strong>Citocinas<\/strong><br>(por exemplo, interfer\u00e3o-\u03b1) para formas espec\u00edficas<\/li>\n\n\n\n<li><strong>Remo\u00e7\u00e3o cir\u00fargica<\/strong><br>para les\u00f5es localizadas&nbsp;<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-27\"><\/span><strong>Previs\u00e3o<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"MALT-Lymphom-2\"><\/span><strong>Linfoma MALT<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Boa previs\u00e3o<\/strong><br>O&nbsp;<strong>Taxa de sobreviv\u00eancia a 10 anos<\/strong>&nbsp;para linfomas isolados tratados \u00e9 de cerca de&nbsp;<strong>75 %<\/strong><br>Sobreviv\u00eancia mediana &gt;10 anos<br>O risco de transforma\u00e7\u00e3o em DLBCL agressivo \u00e9 baixo (aprox. 5-10 %)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"PTLD\"><\/span>PTLD<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Taxa de sobreviv\u00eancia a 1 ano<\/strong>&nbsp;\u00e9 at\u00e9&nbsp;<strong>90 %<\/strong>&nbsp;no caso de PTLD reconhecida e tratada precocemente, consoante o est\u00e1dio e a terap\u00eautica<\/li>\n\n\n\n<li>As PTLD monom\u00f3rficas t\u00eam um pior progn\u00f3stico<\/li>\n\n\n\n<li>A sobreviv\u00eancia a longo prazo \u00e9 comprometida pela imunossupress\u00e3o e pelo risco de infe\u00e7\u00e3o<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Zusammenfassung\"><\/span><strong>Resumo<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><tbody><tr><td class=\"has-text-align-left\" data-align=\"left\">Carater\u00edstica<\/td><td class=\"has-text-align-left\" data-align=\"left\">Linfoma MALT<\/td><td class=\"has-text-align-left\" data-align=\"left\">PTLD<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>A etiologia<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Infe\u00e7\u00e3o cr\u00f3nica (por exemplo.&nbsp;&nbsp;<em>H. pylori<\/em>), autoimune<\/td><td class=\"has-text-align-left\" data-align=\"left\">Infe\u00e7\u00e3o por EBV, imunossupress\u00e3o<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Localiza\u00e7\u00e3o t\u00edpica<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Est\u00f4mago, pulm\u00f5es, anexos oculares, gl\u00e2ndula tiroide<\/td><td class=\"has-text-align-left\" data-align=\"left\">G\u00e2nglios linf\u00e1ticos, f\u00edgado, intestino delgado, pulm\u00f5es<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Clonalidade<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Monoclonal<\/td><td class=\"has-text-align-left\" data-align=\"left\">Oligo-\/policlonal (precoce), monoclonal (tardio)<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Estado do EBV<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Raramente positivo<\/td><td class=\"has-text-align-left\" data-align=\"left\">Maioritariamente positivo (precoce), frequentemente negativo (tardio)<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Lymphomatoide_Granulomatose\"><\/span>Granulomatose linfomat\u00f3ide<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O <strong>Granulomatose linfomat\u00f3ide<\/strong>&nbsp;\u00e9 uma doen\u00e7a linfoproliferativa rara, angioc\u00eantrica e destrutiva que pertence \u00e0s doen\u00e7as proliferativas das c\u00e9lulas B com diferentes graus de potencial maligno.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u00c9 conhecido como&nbsp;<strong>doen\u00e7a sist\u00e9mica granulomatosa<\/strong>&nbsp;com um&nbsp;<strong>Associa\u00e7\u00e3o do v\u00edrus Epstein-Barr (EBV)<\/strong>&nbsp;(detet\u00e1vel pela express\u00e3o de LMP1) e mostra uma&nbsp;<strong>Express\u00e3o de CD20 e CD30<\/strong>&nbsp;das c\u00e9lulas tumorais.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild_und_klinisch-morphologische_Merkmale-6\"><\/span><strong>Quadro cl\u00ednico e carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Manifesta\u00e7\u00f5es cut\u00e2neas<\/strong>&nbsp;ocorrem a cerca de&nbsp;<strong>45 % dos pacientes<\/strong>&nbsp;e s\u00e3o incaracter\u00edsticos:<br>- Sem dor&nbsp;<strong>Manchas, p\u00e1pulas, placas ou n\u00f3dulos castanho-avermelhados<\/strong><br>- Raro:&nbsp;<strong>N\u00f3dulos semelhantes a eritema nodoso<\/strong>&nbsp;com tend\u00eancia para&nbsp;<strong>Ulcera\u00e7\u00e3o<\/strong><br>- Sem epidermotropismo<\/li>\n\n\n\n<li><strong>Envolvimento de \u00f3rg\u00e3os extracut\u00e2neos<\/strong><br>- <strong>pulm\u00e3o<\/strong>Tosse, falta de ar, dor no peito, febre, perda de peso<br>- <strong>Sistema nervoso central (SNC)<\/strong>Em aprox.&nbsp;<strong>26 % dos pacientes<\/strong>&nbsp;- Dores de cabe\u00e7a, ataxia, hemiplegia, c\u00e3ibras<br>- <strong>F\u00edgado e rim<\/strong>Valores laboratoriais patol\u00f3gicos (por exemplo, valores hep\u00e1ticos elevados, insufici\u00eancia renal)<\/li>\n\n\n\n<li><strong>Sintomas gerais<\/strong>Febre, fen\u00f3menos inflamat\u00f3rios inespec\u00edficos, sintomas B (perda de peso, suores noturnos)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_-methodik-9\"><\/span><strong>Diagn\u00f3stico diferencial e metodologia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial \u00e9 crucial, uma vez que o quadro cl\u00ednico \u00e9 inespec\u00edfico.<br>Principais candidatos:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Sarcoidose<\/strong><br>Processos granulomatosos, mas&nbsp;<strong>Sem destrui\u00e7\u00e3o angioc\u00eantrica<\/strong>,&nbsp;<strong>nenhuma associa\u00e7\u00e3o com o EBV<\/strong>,&nbsp;<strong>Sem linf\u00f3citos at\u00edpicos<\/strong><\/li>\n\n\n\n<li><strong>Linfomas de c\u00e9lulas B (especialmente linfoma difuso de grandes c\u00e9lulas B)<\/strong><br>Prolifera\u00e7\u00e3o de c\u00e9lulas B monoclonais,&nbsp;<strong>Aus\u00eancia de estruturas granulomatosas<\/strong>,&nbsp;<strong>maior velocidade de explos\u00e3o<\/strong>&nbsp;(Grau III)<\/li>\n\n\n\n<li><strong>Granulomatose de Wegener (GPA)<\/strong><br><strong>Vasculite de pequenos vasos<\/strong>,&nbsp;<strong>ANCA positivo<\/strong>,&nbsp;<strong>n\u00e3o associada ao VEB<\/strong>,&nbsp;<strong>sem express\u00e3o de CD20<\/strong>&nbsp;das c\u00e9lulas<\/li>\n\n\n\n<li><strong>Linfomas cut\u00e2neos<\/strong><br>Diferencia\u00e7\u00e3o atrav\u00e9s de&nbsp;<strong>Epidermotropismo<\/strong>&nbsp;(ausente na granulomatose linfomat\u00f3ide)<\/li>\n\n\n\n<li><strong>S\u00edndrome de mialgia eosinof\u00edlica<\/strong><br>Sem infiltra\u00e7\u00e3o granulomatosa, geralmente com eosinofilia e mialgia<\/li>\n\n\n\n<li><strong>Granulomatoses infecciosas<\/strong><br>(por exemplo, tuberculose, histoplasmose)<br>Dete\u00e7\u00e3o de agentes patog\u00e9nicos no tecido.&nbsp;<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>M\u00e9todos de diagn\u00f3stico<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Bi\u00f3psia de pele e de \u00f3rg\u00e3os<\/strong>&nbsp;(pulm\u00e3o, rim) com an\u00e1lise histol\u00f3gica<\/li>\n\n\n\n<li><strong>Imunohistoqu\u00edmica<\/strong><br>CD20+, CD30+, LMP1+ (EBV)<\/li>\n\n\n\n<li><strong>An\u00e1lise biol\u00f3gica molecular<\/strong><br>Dete\u00e7\u00e3o do ADN do EBV em tecidos<\/li>\n\n\n\n<li><strong>Imagiologia<\/strong><br>TC\/RM (pulm\u00f5es, SNC), PET-CT para estadiamento e monitoriza\u00e7\u00e3o da terap\u00eautica (por exemplo, aumento da capta\u00e7\u00e3o de FDG)<\/li>\n\n\n\n<li><strong>Laborat\u00f3rio<\/strong><br>Par\u00e2metros inflamat\u00f3rios elevados (CRP, SED),&nbsp;<strong>serologia positiva para o EBV<\/strong>, LDH elevada<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-29\"><\/span><strong>Terapia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Existe&nbsp;<strong>Nenhum padr\u00e3o terap\u00eautico estabelecido<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A terapia baseia-se na&nbsp;<strong>Est\u00e1dio histol\u00f3gico<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Grau I<\/strong>&nbsp;(Baixo grau)<br>- <strong>Espera vigilante<\/strong>&nbsp;com imunomodula\u00e7\u00e3o (por exemplo, melhoria do estado imunit\u00e1rio), uma vez que s\u00e3o poss\u00edveis remiss\u00f5es espont\u00e2neas.<\/li>\n\n\n\n<li><strong>Graus II e III<\/strong>&nbsp;(alto grau) ou m\u00faltiplos \u00f3rg\u00e3os afectados<br>- <strong>Terapia combinada<\/strong>:&nbsp;<strong>Regime CHOP<\/strong>&nbsp;(ciclofosfamida, doxorrubicina, vincristina, prednisona) ou&nbsp;<strong>R-CHOP<\/strong>&nbsp;(com rituximab)<br>- <strong>Terapia imunossupressora<\/strong>&nbsp;para&nbsp;<strong>Esquema Fauci<\/strong>&nbsp;(prednisona + ciclofosfamida)<br>- <strong>Terapia agressiva para recorr\u00eancia ou grau III<\/strong><br>\u2013 \u2013 <strong>Quimioterapia de alta dose<\/strong>&nbsp;(por exemplo, BEAM) +&nbsp;<strong>Transplante aut\u00f3logo de c\u00e9lulas estaminais (ASCT)<\/strong><br>\u2013 \u2013 <strong>Radioimunoterapia<\/strong>&nbsp;com&nbsp;<strong>Y-90-Ibritumomab-Tiuxetan<\/strong>&nbsp;em combina\u00e7\u00e3o com ASCT (comprovado para recorr\u00eancias)<br>\u2013 \u2013 <strong>Interfer\u00e3o-\u03b12b<\/strong>&nbsp;como op\u00e7\u00e3o adicional (comprovadamente eficaz em casos individuais)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-28\"><\/span><strong>Previs\u00e3o<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Progress\u00e3o vari\u00e1vel<\/strong><br>Poss\u00edvel&nbsp;<strong>Remiss\u00f5es espont\u00e2neas<\/strong>, mas tamb\u00e9m&nbsp;<strong>r\u00e1pida progress\u00e3o<\/strong><\/li>\n\n\n\n<li><strong>Complica\u00e7\u00e3o frequente<\/strong><br>Desenvolvimento de um&nbsp;<strong>linfoma agressivo de c\u00e9lulas B<\/strong>&nbsp;(por exemplo, linfoma difuso de grandes c\u00e9lulas B)<\/li>\n\n\n\n<li><strong>Causa da morte<\/strong><br>Principalmente&nbsp;<strong>insufici\u00eancia respirat\u00f3ria<\/strong>&nbsp;ou&nbsp;<strong>complica\u00e7\u00f5es s\u00e9pticas<\/strong><\/li>\n\n\n\n<li><strong>Taxa de sobreviv\u00eancia a longo prazo<\/strong><br>Aprox.&nbsp;<strong>25 %<\/strong>&nbsp;(consoante a gravidade e a resposta \u00e0 terap\u00eautica)<\/li>\n\n\n\n<li><strong>Factores de progn\u00f3stico<\/strong><br>Est\u00e1dio, envolvimento de \u00f3rg\u00e3os (especialmente o SNC), carga de EBV, valores de LDH.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Um&nbsp;<strong>Confirma\u00e7\u00e3o histol\u00f3gica precoce<\/strong>&nbsp;e&nbsp;<strong>terapia multimodal<\/strong>&nbsp;s\u00e3o decisivos para o progn\u00f3stico.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Bi\u00f3psias cut\u00e2neas<\/strong>&nbsp;pode fornecer a pista decisiva, mas&nbsp;<strong>Participa\u00e7\u00e3o sist\u00e9mica<\/strong>&nbsp;deve ser sempre esclarecido.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"GANZL\"><span class=\"ez-toc-section\" id=\"Granulomatose_mit_organerhaltender_Vaskulitis_GANZL\"><\/span>Granulomatose com vasculite preservadora de \u00f3rg\u00e3os (GANZL)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">A granulomatose com poliangiite (GPA), anteriormente tamb\u00e9m conhecida como doen\u00e7a de Wegener, \u00e9 uma vasculite rara, sist\u00e9mica e necrosante de pequenos vasos causada por uma&nbsp;<strong>Inflama\u00e7\u00e3o granulomatosa extravascular<\/strong>&nbsp;no trato respirat\u00f3rio e um&nbsp;<strong>Vasculite de vasos pequenos e m\u00e9dios<\/strong>&nbsp;\u00e9 rotulado.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Pertence ao grupo das vasculites associadas a ANCA (AAV) e est\u00e1 tipicamente associada a&nbsp;<strong>PR3-ANCA<\/strong>&nbsp;associado.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild_und_klinisch-morphologische_Merkmale-7\"><\/span>Quadro cl\u00ednico e carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O quadro cl\u00ednico varia consoante o envolvimento dos \u00f3rg\u00e3os, sendo o&nbsp;<strong>s\u00edndrome pulmonar-renal<\/strong>&nbsp;(hemorragia alveolar, glomerulonefrite rapidamente progressiva) e a&nbsp;<strong>Envolvimento do trato respirat\u00f3rio superior<\/strong>&nbsp;s\u00e3o t\u00edpicos.&nbsp;<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Trato respirat\u00f3rio superior<\/strong><br>Rinite sanguinolenta recorrente, hemorragias nasais, crostas nasais, mucosa com aspeto granulado,&nbsp;<strong>Nariz de sela<\/strong>&nbsp;(colapso da ponte nasal), sinusite, estenose subgl\u00f3tica<\/li>\n\n\n\n<li><strong>Trato respirat\u00f3rio inferior<\/strong><br>Tosse, hemoptise, n\u00f3dulos pulmonares com cavita\u00e7\u00e3o, altera\u00e7\u00f5es pulmonares intersticiais, hemorragia alveolar (dispneia aguda, sangue na expetora\u00e7\u00e3o)<\/li>\n\n\n\n<li><strong>Rins<\/strong><br>Glomerulonefrite com glomerulonefrite necrosante focal, frequentemente com forma\u00e7\u00e3o de crescentes, hipertens\u00e3o, edema, creatinina s\u00e9rica elevada<\/li>\n\n\n\n<li><strong>pele<\/strong><br>P\u00farpura palp\u00e1vel, n\u00f3dulos subcut\u00e2neos, pioderma gangraenosum<\/li>\n\n\n\n<li><strong>Sistema nervoso<\/strong><br>Mononeurite m\u00faltipla, paralisias dos nervos cranianos<\/li>\n\n\n\n<li><strong>Olhos<\/strong><br>Conjuntivite, esclerite, uve\u00edte, infiltra\u00e7\u00f5es retro-orbit\u00e1rias (exoftalmia, perturba\u00e7\u00f5es visuais)<\/li>\n\n\n\n<li><strong>Outros \u00f3rg\u00e3os<\/strong><br>Cora\u00e7\u00e3o (raramente envolvimento coron\u00e1rio), articula\u00e7\u00f5es (artrite n\u00e3o erosiva), f\u00edgado, ba\u00e7o<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Histologicamente, a biopsia revela uma&nbsp;<strong>Vasculite necrosante dos pequenos e m\u00e9dios vasos<\/strong>, inflama\u00e7\u00e3o granulomatosa com c\u00e9lulas epitelioides, c\u00e9lulas gigantes e&nbsp;<strong>necrose geogr\u00e1fica<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">No entanto, a tr\u00edade cl\u00e1ssica (inflama\u00e7\u00e3o granulomatosa, vasculite necrosante, necrose geogr\u00e1fica) n\u00e3o est\u00e1 presente na&nbsp;<strong>GPA localizado<\/strong>&nbsp;raramente detet\u00e1vel.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnose_und_-methodik\"><\/span>Diagn\u00f3stico diferencial e metodologia<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico requer um esclarecimento diferenciado, uma vez que muitas doen\u00e7as t\u00eam sintomas semelhantes.&nbsp;<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Sintomas cl\u00ednicos<\/strong><br>(por exemplo, hemorragias nasais, n\u00f3dulos pulmonares, glomerulonefrite) devem ser diferenciadas de outras causas<\/li>\n\n\n\n<li><strong>Testes serol\u00f3gicos<\/strong>: Prova de&nbsp;<strong>PR3-ANCA<\/strong>&nbsp;(espec\u00edfico para GPA) ou MPO-ANCA (para MPA\/EGPA)<br>A positividade ANCA n\u00e3o \u00e9 100 % certa, uma vez que tamb\u00e9m ocorrem casos ANCA-negativos<\/li>\n\n\n\n<li><strong>Bi\u00f3psia<\/strong><br><strong>Amostras de tecido dos \u00f3rg\u00e3os afectados<\/strong> (por exemplo, nariz, pulm\u00e3o, rim) s\u00e3o o padr\u00e3o de ouro para confirmar o diagn\u00f3stico.<br>Histologicamente detet\u00e1vel: vasculite necrosante, inflama\u00e7\u00e3o granulomatosa<\/li>\n\n\n\n<li><strong>Procedimentos de imagiologia<\/strong><br>TAC do t\u00f3rax (n\u00f3dulos pulmonares, cavita\u00e7\u00e3o), RMN (por exemplo, c\u00e9rebro, nervos), ultra-sons (rins)<\/li>\n\n\n\n<li><strong>Exame do l\u00edquido cefalorraquidiano<\/strong><br>Em caso de sintomas neurol\u00f3gicos: aumento da contagem de c\u00e9lulas e prote\u00ednas (LCR inflamat\u00f3rio), mas sem bandas oligoclonais<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Diagn\u00f3sticos diferenciais<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Infec\u00e7\u00f5es<\/strong><br>Tuberculose, infec\u00e7\u00f5es f\u00fangicas (por exemplo, aspergilose), endocardite bacteriana<\/li>\n\n\n\n<li><strong>Outras vasculites<\/strong><br>Arterite de c\u00e9lulas gigantes, arterite de Takayasu, poliarterite nodosa<\/li>\n\n\n\n<li><strong>Doen\u00e7as auto-imunes<\/strong><br>L\u00fapus eritematoso sist\u00e9mico (LES), s\u00edndrome de Sj\u00f6gren<\/li>\n\n\n\n<li><strong>Tumores<\/strong><br>Linfoma, carcinoma (especialmente pulmonar)<\/li>\n\n\n\n<li><strong>Granulomas infecciosos<\/strong><br>Tuberculose, sarcoidose<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-30\"><\/span>Terapia<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O tratamento depende da gravidade e do envolvimento dos \u00f3rg\u00e3os e divide-se em&nbsp;<strong>Indu\u00e7\u00e3o da remiss\u00e3o<\/strong>&nbsp;e&nbsp;<strong>Manuten\u00e7\u00e3o da remiss\u00e3o<\/strong>.<br><br><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Indu\u00e7\u00e3o da remiss\u00e3o<\/strong>&nbsp;(em caso de doen\u00e7a grave)<br>- <strong>Rituximab<\/strong>&nbsp;(anticorpo anti-CD20) ou&nbsp;<strong>Ciclofosfamida<\/strong>&nbsp;(em combina\u00e7\u00e3o com&nbsp;<strong>Glucocortic\u00f3ides<\/strong>, por exemplo, prednisona)<br>- Em caso de hemorragia alveolar grave ou glomerulonefrite rapidamente progressiva:&nbsp;<strong>Troca de plasma<\/strong><\/li>\n\n\n\n<li><strong>Manuten\u00e7\u00e3o da remiss\u00e3o<\/strong><br>- <strong>Azatioprina<\/strong>&nbsp;ou&nbsp;<strong>Metotrexato<\/strong>&nbsp;(efetivo)<br>- <strong>Micofenolato de mofetil<\/strong>&nbsp;(menos eficaz)<br>- <strong>Rituximab<\/strong>&nbsp;tamb\u00e9m para terapia de manuten\u00e7\u00e3o (para pacientes PR3-ANCA-positivos)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-29\"><\/span>Previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Com as terapias modernas, pode conseguir&nbsp;<strong>mais de 80 % dos doentes atingem a remiss\u00e3o<\/strong><\/li>\n\n\n\n<li><strong>As recorr\u00eancias s\u00e3o frequentes<\/strong>, especialmente com positividade para PR3-ANCA, envolvimento pulmonar ou envolvimento do trato respirat\u00f3rio superior<\/li>\n\n\n\n<li><strong>Factores de progn\u00f3stico para um mau resultado<\/strong><br>- Fun\u00e7\u00e3o renal deficiente na altura do diagn\u00f3stico (por exemplo, necessidade de di\u00e1lise)<br>- Atividade elevada da doen\u00e7a (Birmingham Vasculitis Activity Score)<br>- Manifesta\u00e7\u00f5es card\u00edacas ou gastrointestinais<br>- Idade &gt;65 anos<br>- Glomerulonefrite esclerosante na biopsia<\/li>\n\n\n\n<li><strong>Mortalidade<\/strong><br>est\u00e1 aumentado, especialmente com envolvimento renal grave ou infec\u00e7\u00f5es (associadas \u00e0 terap\u00eautica)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">A GPA \u00e9 uma doen\u00e7a complexa, de m\u00faltiplos \u00f3rg\u00e3os, cujo diagn\u00f3stico se baseia numa combina\u00e7\u00e3o de apresenta\u00e7\u00e3o cl\u00ednica, serologia ANCA e&nbsp;<strong>altera\u00e7\u00e3o histol\u00f3gica confirmada por bi\u00f3psia<\/strong>&nbsp;\u00e9 baseado em.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A terapia precoce e centralizada com imunossupressores \u00e9 crucial para um progn\u00f3stico favor\u00e1vel.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"IEG_EBVBL\"><span class=\"ez-toc-section\" id=\"EBV-assoziierte_B-Zell-Lymphoproliferationen\"><\/span>Linfoprolifera\u00e7\u00f5es de c\u00e9lulas B associadas ao EBV<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">As linfoprolifera\u00e7\u00f5es de c\u00e9lulas B associadas ao v\u00edrus Epstein-Barr (EBV) compreendem um espetro de doen\u00e7as que diferem na sua biologia, manifesta\u00e7\u00e3o cl\u00ednica e progn\u00f3stico.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A diferencia\u00e7\u00e3o \u00e9 crucial para a decis\u00e3o de tratamento.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\" id=\"klinisches-bild-und-morphologische-merkmale\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild_und_morphologische_Merkmale-3\"><\/span><strong>Quadro cl\u00ednico e carater\u00edsticas morfol\u00f3gicas<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Doen\u00e7as linfoproliferativas p\u00f3s-transplante (PTLD)<\/strong><br>Ocorre ap\u00f3s o transplante de \u00f3rg\u00e3os s\u00f3lidos ou de c\u00e9lulas estaminais hematopoi\u00e9ticas. O quadro cl\u00ednico depende da fase da doen\u00e7a:<br>- <strong>Les\u00f5es precoces (aprox. 5%)<\/strong><br>Oligo- ou policlonal,&nbsp;<strong>quase sempre EBV-positivo<\/strong>, frequentemente com expans\u00e3o monoclonal de c\u00e9lulas B. Morfologicamente, apresentam uma prolifera\u00e7\u00e3o infiltrativa difusa de linf\u00f3citos com atipia celular<br>- <strong>PTLD poli e monom\u00f3rfica<\/strong><br>\u2013 \u2013 <em>PTLD policlonal<\/em>:&nbsp;<strong>EBV-positivo ou -negativo<\/strong>, frequentemente com prolifera\u00e7\u00e3o policlonal de c\u00e9lulas B<br>\u2013 \u2013 <em>PTLD monom\u00f3rfica<\/em>:&nbsp;<strong>frequentemente EBV-negativo<\/strong>&nbsp;(at\u00e9 50%), monoclonal, morfologicamente semelhante a um&nbsp;<strong>linfoma difuso de grandes c\u00e9lulas B (DLBCL)<\/strong>, frequentemente com morfologia imunobl\u00e1stica ou anapl\u00e1sica<\/li>\n\n\n\n<li><strong>DLBCL positivo para o v\u00edrus Epstein-Barr em pessoas idosas<\/strong><br>- Principalmente reuni\u00f5es&nbsp;<strong>adultos mais velhos<\/strong>&nbsp;(maioritariamente &gt;60 anos), frequentemente&nbsp;<strong>n\u00e3o imunocomprometidos<\/strong><br>- Cl\u00ednica<br>\u2013 \u2013 <strong>Manifesta\u00e7\u00f5es extranodais<\/strong>&nbsp;(por exemplo, pele, trato gastrointestinal, SNC)<br>\u2013 \u2013 <strong>Sintomas B<\/strong>&nbsp;(febre, suores noturnos, perda de peso)<br>\u2013 \u2013 <strong>Progress\u00e3o r\u00e1pida<\/strong><br>- Morfologia<br>\u2013 \u2013 <strong>Popula\u00e7\u00e3o difusa de c\u00e9lulas grandes<\/strong>&nbsp;com atipia centrobl\u00e1stica ou imunobl\u00e1stica<br>\u2013 \u2013 <strong>Elevada taxa de prolifera\u00e7\u00e3o<\/strong>&nbsp;(Ki67 &gt;90%)<\/li>\n\n\n\n<li><strong>Linfoma cut\u00e2neo prim\u00e1rio agressivo de c\u00e9lulas B (DLBCL cut\u00e2neo prim\u00e1rio, extremidade inferior)<\/strong><br>- <strong>Infesta\u00e7\u00e3o extralinf\u00e1tica<\/strong>&nbsp;(pele, especialmente pernas), principalmente&nbsp;<strong>n\u00e3o sist\u00e9mico<\/strong>, frequentemente&nbsp;<strong>apenas um \u00fanico fog\u00e3o<\/strong><br>- <strong>EBV-positivo<\/strong>&nbsp;em doentes idosos,&nbsp;<strong>EBV-negativo<\/strong>&nbsp;para os mais jovens<br>- Morfologia<br>\u2013 \u2013 <strong>prolifera\u00e7\u00e3o difusa de grandes c\u00e9lulas B<\/strong>&nbsp;com express\u00e3o de tipos de c\u00e9lulas (por exemplo, imunobl\u00e1sticas)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\" id=\"differenzialdiagnostik-und-methodik\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_Methodik-2\"><\/span><strong>Diagn\u00f3stico diferencial e metodologia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Citomorfologia<\/strong><br>- <strong>DLBCL, NOS<\/strong>&nbsp;vs.&nbsp;<strong>EBV+ DLBCL<\/strong><br>A morfologia por si s\u00f3 n\u00e3o \u00e9 suficiente para diferenciar<br>- <strong>PTLD vs. DLBCL<\/strong><br>A cl\u00ednica (hist\u00f3ria de transplante), a clonalidade (PCR) e o estatuto do EBV (EBER-ISH) s\u00e3o decisivos<\/li>\n\n\n\n<li><strong>Imunofenotipagem<\/strong><br>- <strong>Todos os linfomas associados ao EBV<\/strong><br>\u2013 \u2013 <strong>CD20+<\/strong>,&nbsp;<strong>CD79a+<\/strong>,&nbsp;<strong>PAX5+<\/strong>,&nbsp;<strong>CD45+<\/strong>,&nbsp;<strong>CD10+<\/strong>&nbsp;(para o subtipo GCB)<br>\u2013 \u2013 <strong>BCL6+<\/strong>,&nbsp;<strong>CD30+<\/strong>&nbsp;(para 10-20% de casos)<br>- <strong>EBV+ DLBCL em idosos<\/strong><br>\u2013 \u2013 <strong>CD30+<\/strong>&nbsp;em at\u00e9 70% dos casos<br>\u2013 \u2013 <strong>CD5-<\/strong>,&nbsp;<strong>CD138-<\/strong>,&nbsp;<strong>MYC-<\/strong>&nbsp;(n\u00e3o \u00e9 de dupla express\u00e3o)<\/li>\n\n\n\n<li><strong>M\u00e9todos gen\u00e9ticos e de biologia molecular<\/strong><br>- <strong>EBER-ISH (hibrida\u00e7\u00e3o in situ do ARN codificado pelo v\u00edrus Epstein-Barr)<\/strong>,<strong> Dete\u00e7\u00e3o do EBV<\/strong>&nbsp;nas c\u00e9lulas<br>- <strong>PEIXE<\/strong><br>Exclus\u00e3o de&nbsp;<strong>Transloca\u00e7\u00f5es MYC\/BCL2<\/strong>&nbsp;(ent\u00e3o:&nbsp;<strong>Linfoma de duplo efeito<\/strong>)<br>- <strong>PCR para o ADN do EBV<\/strong><br>Quantifica\u00e7\u00e3o no soro\/plasma (n\u00e3o apenas para diagn\u00f3stico, mas para monitoriza\u00e7\u00e3o)<br>- <strong>An\u00e1lise da express\u00e3o gen\u00e9tica (subtipo COO)<\/strong><br>\u2013 \u2013 <strong>Subtipo GCB<\/strong>&nbsp;(c\u00e9lulas B do centro germinal) - mais comum em&nbsp;<strong>EBV+ DLBCL em idosos<\/strong><br>\u2013 \u2013 <strong>Subtipo ABC<\/strong>&nbsp;(c\u00e9lulas B activadas) - mais comum em&nbsp;<strong>PTLD<\/strong><\/li>\n\n\n\n<li><strong>Diagn\u00f3stico diferencial<\/strong><br>- <strong>DLBCL, NOS<\/strong>Sem associa\u00e7\u00e3o com o EBV, frequentemente com transloca\u00e7\u00f5es MYC\/BCL2<br>- <strong>Linfoma de Burkitt<\/strong><br>\u2013 \u2013 <strong>Taxa de prolifera\u00e7\u00e3o extremamente elevada (Ki67 &gt;95%)<\/strong>,&nbsp;<strong>Transloca\u00e7\u00e3o MYC<\/strong>,&nbsp;<strong>\u201epadr\u00e3o \u201cc\u00e9u estrelado<\/strong>,&nbsp;<strong>CD10+<\/strong>,&nbsp;<strong>BCL6+<\/strong>,&nbsp;<strong>CD5-<\/strong><br>- <strong>Linfoma anapl\u00e1sico de grandes c\u00e9lulas (ALCL)<\/strong><br>\u2013 \u2013 <strong>CD30+<\/strong>,&nbsp;<strong>ALK+<\/strong>&nbsp;(para ALCL ALK-positivo),&nbsp;<strong>CD15+<\/strong>,&nbsp;<strong>Fen\u00f3tipo das c\u00e9lulas T<\/strong><br>- <strong>Linfoma de Hodgkin<\/strong><br>\u2013 \u2013 <strong>CD15+<\/strong>,&nbsp;<strong>CD30+<\/strong>,&nbsp;<strong>CD20-<\/strong>,&nbsp;<strong>CD45-<\/strong>,&nbsp;<strong>C\u00e9lulas de Reed-Sternberg<\/strong><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\" id=\"therapie\"><span class=\"ez-toc-section\" id=\"Therapie-31\"><\/span><strong>Terapia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>PTLD<\/strong><br>- <strong>Primeira linha<\/strong><br>\u2013 \u2013 <strong>Redu\u00e7\u00e3o da imunossupress\u00e3o<\/strong>&nbsp;(se poss\u00edvel)<br>\u2013 \u2013 <strong>Rituximab (monoclonal)<\/strong>, <strong>Primeira escolha<\/strong>&nbsp;para EBV+ PTLD<br>\u2013 \u2013 <strong>Fase avan\u00e7ada<\/strong><br>\u2013 \u2013 \u2013 <strong>R-CHOP<\/strong>&nbsp;ou&nbsp;<strong>Regimes do tipo R-CHOP<\/strong><br>\u2013 \u2013 <strong>Para os casos que n\u00e3o respondem<\/strong><br>\u2013 \u2013 \u2013 <strong>Quimioterapia<\/strong>,&nbsp;<strong>Terapia celular (por exemplo, c\u00e9lulas CAR-T)<\/strong>.<\/li>\n\n\n\n<li><strong>EBV+ DLBCL em idosos<\/strong><br>- <strong>R-CHOP<\/strong>&nbsp;(rituximab, ciclofosfamida, doxorrubicina, vincristina, prednisona)<br>- Para doentes com&nbsp;<strong>risco elevado (por exemplo, IPI elevado)<\/strong> <strong>Terapia intensificada (por exemplo, DA-EPOCH-R)<\/strong><br>- <strong>C\u00e9lulas CAR-T<\/strong>&nbsp;em caso de recidiva\/doen\u00e7a refract\u00e1ria<\/li>\n\n\n\n<li><strong>DLBCL cut\u00e2neo prim\u00e1rio, extremidade inferior<\/strong><br>- <strong>Terapia local (radioterapia)<\/strong>&nbsp;Com infesta\u00e7\u00e3o limitada<br>- <strong>Terapia sist\u00e9mica (R-CHOP)<\/strong>&nbsp;para les\u00f5es m\u00faltiplas ou sist\u00e9micas<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\" id=\"prognose\"><span class=\"ez-toc-section\" id=\"Prognose-30\"><\/span><strong>Previs\u00e3o<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<h5 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"PTLD-2\"><\/span>PTLD<span class=\"ez-toc-section-end\"><\/span><\/h5>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Favor\u00e1vel<\/strong>&nbsp;com diagn\u00f3stico precoce e redu\u00e7\u00e3o da imunossupress\u00e3o<\/li>\n\n\n\n<li><strong>Taxa de sobreviv\u00eancia a 5 anos<\/strong>: aprox.&nbsp;<strong>60-70%<\/strong>, consoante o est\u00e1dio e a resposta \u00e0 terap\u00eautica<\/li>\n<\/ul>\n\n\n\n<h5 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"EBV_DLBCL_des_alteren_Menschen\"><\/span><strong>EBV+ DLBCL em idosos<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h5>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Previs\u00e3o mais fraca<\/strong>&nbsp;em compara\u00e7\u00e3o com o DLBCL negativo para EBV (especialmente em doentes mais velhos).&nbsp;<\/li>\n\n\n\n<li><strong>Taxa de sobreviv\u00eancia a 5 anos<\/strong>: aprox.&nbsp;<strong>40-50%<\/strong>.<\/li>\n<\/ul>\n\n\n\n<h5 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Primar_kutanes_DLBCL_untere_Extremitat\"><\/span><strong>DLBCL cut\u00e2neo prim\u00e1rio, extremidade inferior<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h5>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Previs\u00e3o mais favor\u00e1vel<\/strong>, se limitado localmente<\/li>\n\n\n\n<li><strong>Taxa de sobreviv\u00eancia a 5 anos<\/strong>&gt;80% com terapia local<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial do linfoma de c\u00e9lulas B associado ao EBV requer um diagn\u00f3stico multimodal (histologia, imunofen\u00f3tipo, EBER-ISH, FISH, an\u00e1lise da express\u00e3o gen\u00e9tica).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A terap\u00eautica baseia-se na cl\u00ednica, na classifica\u00e7\u00e3o do est\u00e1dio e no perfil de risco, sendo o rituximab e o R-CHOP os principais componentes terap\u00eauticos.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">O progn\u00f3stico varia muito consoante o subtipo e \u00e9 geralmente menos favor\u00e1vel em compara\u00e7\u00e3o com o DLBCL negativo para o EBV, especialmente em doentes mais velhos.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Hodgkin-Lymphom\"><\/span><strong>Linfoma de Hodgkin<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"cHL_NS\"><span class=\"ez-toc-section\" id=\"Klassisches_Hodgkin-Lymphom_nodulare_Sklerose_cHL_NS\"><\/span>Linfoma de Hodgkin cl\u00e1ssico, esclerose nodular (cHL, NS)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O linfoma de Hodgkin cl\u00e1ssico (LHc) com esclerose nodular \u00e9 o tipo mais comum de linfoma.&nbsp;<strong>subtipo mais comum<\/strong>&nbsp;de cHL, com uma preval\u00eancia de cerca de&nbsp;<strong>70 %<\/strong>&nbsp;nos pa\u00edses ocidentais.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Mostra um&nbsp;<strong>distribui\u00e7\u00e3o et\u00e1ria bimodal<\/strong>&nbsp;com um pico de ocorr\u00eancia entre os 20 e os 30 anos e um segundo pico ap\u00f3s os 65 anos.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild-4\"><\/span>Imagem cl\u00ednica<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Sintomatologia<\/strong><br>Aumento indolor dos g\u00e2nglios linf\u00e1ticos, frequentemente no pesco\u00e7o e na regi\u00e3o cervical, supraclavicular e no mediastino.<br>Um&nbsp;<strong>B-sintom\u00e1ticos<\/strong>&nbsp;(febre, suores noturnos, perda de peso &gt;10 %) est\u00e1 presente em cerca de 50 % dos doentes.<\/li>\n\n\n\n<li><strong>Localiza\u00e7\u00e3o<\/strong><br>Infesta\u00e7\u00e3o preferencial de&nbsp;<strong>g\u00e2nglios linf\u00e1ticos mediastinais<\/strong>, que conduz a uma massa tumoral mediast\u00ednica t\u00edpica (em cerca de 80 % dos casos).<\/li>\n\n\n\n<li><strong>Resultados laboratoriais<\/strong><br>A anemia e\/ou o prurido ocorrem em cerca de um quarto dos doentes.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisch-morphologische_Merkmale-9\"><\/span>Carater\u00edsticas cl\u00ednico-morfol\u00f3gicas<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Histologia<\/strong><br>Caracterizado por um&nbsp;<strong>padr\u00e3o de crescimento nodular<\/strong>,&nbsp;<strong>esclerose pronunciada<\/strong>&nbsp;(fios de tecido conjuntivo colag\u00e9nico) e&nbsp;<strong>C\u00e9lulas lacunares<\/strong>&nbsp;(uma forma especial de c\u00e9lulas de Hodgkin-Reed-Sternberg que apresentam um citoplasma opticamente vazio durante a fixa\u00e7\u00e3o em formalina)<\/li>\n\n\n\n<li><strong>Popula\u00e7\u00e3o celular<\/strong><br>Apenas cerca de&nbsp;<strong>1 % das c\u00e9lulas<\/strong>&nbsp;s\u00e3o c\u00e9lulas tumorais malignas (c\u00e9lulas de Hodgkin-Reed-Sternberg). O restante \u00e9 constitu\u00eddo por&nbsp;<strong>infiltrado misto<\/strong>&nbsp;c\u00e9lulas reactivas: Linf\u00f3citos, plasm\u00f3citos, granul\u00f3citos eosin\u00f3filos e histi\u00f3citos<\/li>\n\n\n\n<li><strong>Imunofen\u00f3tipo das c\u00e9lulas tumorais<\/strong><br>- <strong>CD30+<\/strong>,&nbsp;<strong>CD15+<\/strong>,&nbsp;<strong>PD-L1+<\/strong>,&nbsp;<strong>MUM1+<\/strong><br>- <strong>CD20-\/+<\/strong>&nbsp;(positivo em cerca de 20 %),&nbsp;<strong>CD45-<\/strong><br>- <strong>EBV-<\/strong>&nbsp;ou&nbsp;<strong>EBV+<\/strong>&nbsp;(em n\u00fameros vari\u00e1veis)<br>- <strong>Cadeia J<\/strong><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-22\"><\/span>Diagn\u00f3stico diferencial<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial \u00e9 crucial devido \u00e0 semelhan\u00e7a cl\u00ednica e histol\u00f3gica com outras doen\u00e7as:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Mononucleose infecciosa<\/strong>&nbsp;(associada ao EBV)<br>Diferencia\u00e7\u00e3o por quadro cl\u00ednico, achados serol\u00f3gicos (anticorpos heter\u00f3filos) e aus\u00eancia de popula\u00e7\u00e3o celular clonal<\/li>\n\n\n\n<li><strong>Linfoma folicular<\/strong><br>Diferencia\u00e7\u00e3o por aus\u00eancia de c\u00e9lulas Reed-Sternberg, padr\u00e3o de crescimento folicular t\u00edpico e imunofen\u00f3tipo CD10+\/CD20+\/BCL2<\/li>\n\n\n\n<li><strong>Linfoma de Hodgkin com predomin\u00e2ncia de linf\u00f3citos (NLPHL)<\/strong><br>Diferencia\u00e7\u00e3o por aus\u00eancia de express\u00e3o de CD30\/CD15, express\u00e3o positiva da cadeia CD20\/CD45\/J e c\u00e9lulas L&amp;H t\u00edpicas (c\u00e9lulas ricas em linf\u00f3citos e histi\u00f3citos)<\/li>\n\n\n\n<li><strong>Linfoma agressivo de grandes c\u00e9lulas B rico em histi\u00f3citos de c\u00e9lulas T (TCHRBCL)<\/strong><br>Diferencia\u00e7\u00e3o devido \u00e0 falta de express\u00e3o de CD30\/CD15 nas c\u00e9lulas tumorais e noutros imunofen\u00f3tipos (por exemplo, CD5+, CD10-)<\/li>\n\n\n\n<li><strong>Progress\u00e3o dos centros germinais reactivos (PTKZ)<\/strong><br>Diferencia\u00e7\u00e3o por aus\u00eancia de popula\u00e7\u00e3o de c\u00e9lulas clonais e aus\u00eancia de c\u00e9lulas HRS t\u00edpicas<\/li>\n\n\n\n<li><strong>Doen\u00e7as associadas ao EBV<\/strong>&nbsp;(por exemplo, \u00falcera mucocut\u00e2nea EBV-positiva)<br>Diferencia\u00e7\u00e3o por quadro cl\u00ednico, localiza\u00e7\u00e3o e dete\u00e7\u00e3o do ADN do EBV<\/li>\n\n\n\n<li><strong>Linfoma anapl\u00e1sico de grandes c\u00e9lulas (ALK-negativo)<\/strong><br>Nos LHC pobres em linf\u00f3citos, especialmente em doentes seropositivos, \u00e9 necess\u00e1ria uma diferencia\u00e7\u00e3o<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostik-6\"><\/span>Diagn\u00f3stico<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Bi\u00f3psia<\/strong><br>Diagn\u00f3stico prim\u00e1rio por biopsia de g\u00e2nglios linf\u00e1ticos (geralmente mediast\u00ednicos ou cervicais)<\/li>\n\n\n\n<li><strong>Imunohistoqu\u00edmica<\/strong><br>Crucial para a confirma\u00e7\u00e3o do imunofen\u00f3tipo (CD30, CD15, CD20, CD45, PD-L1).<\/li>\n\n\n\n<li><strong>Imagiologia<\/strong><br>Tomografia computorizada (TC) do t\u00f3rax, pesco\u00e7o, abd\u00f3men e p\u00e9lvis; tomografia por emiss\u00e3o de positr\u00f5es (PET) para estadiamento e monitoriza\u00e7\u00e3o da terap\u00eautica<\/li>\n\n\n\n<li><strong>Bi\u00f3psia da medula \u00f3ssea<\/strong><br>Apenas indicado para sintomas B ou valores laboratoriais anormais<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-32\"><\/span>Terapia<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Stadienadaptierte_Therapie\"><\/span><strong>Terapia adaptada \u00e0 fase<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Estadio I\/II sem factores de risco<\/strong><br>Radioterapia e quimioterapia combinadas (por exemplo, ABVD + Radioterapia de campo envolvido)<\/li>\n\n\n\n<li><strong>Estadio I\/II com factores de risco ou estadio III\/IV<\/strong><br>Quimioterapia (por exemplo, ABVD) com ou sem radioterapia<\/li>\n\n\n\n<li><strong>Novas terapias<\/strong><br>Conjugados citost\u00e1ticos de anticorpos anti-CD30 (por exemplo, brentuximab vedotina) na terap\u00eautica de recupera\u00e7\u00e3o<\/li>\n\n\n\n<li><strong>Objetivo<\/strong><br>Sobreviv\u00eancia a longo prazo de&nbsp;<strong>80-90 %<\/strong>&nbsp;com terapia adequada<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-31\"><\/span>Previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Sem tratamento&nbsp;<strong>moderadamente agressivo<\/strong><\/li>\n\n\n\n<li>Com tratamento&nbsp;<strong>extremamente favor\u00e1vel<\/strong>, sobre&nbsp;<strong>80 % dos pacientes<\/strong>&nbsp;s\u00e3o curados a longo prazo<\/li>\n\n\n\n<li>O&nbsp;<strong>Subclassifica\u00e7\u00e3o histol\u00f3gica (por exemplo, esclerose nodular)<\/strong>&nbsp;tem&nbsp;<strong>Sem relev\u00e2ncia terap\u00eautica<\/strong>&nbsp;Atualmente, o tratamento \u00e9 adaptado \u00e0 fase e ao risco.&nbsp;<\/li>\n<\/ul>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\"><strong>Perceber<\/strong>O diagn\u00f3stico diferencial requer um&nbsp;<strong>Esclarecimento multidisciplinar<\/strong>&nbsp;por patologia, hematologia e oncologia.  Os&nbsp;<strong>Diagn\u00f3stico precoce e correto<\/strong>&nbsp;\u00e9 crucial para o sucesso da terapia.<\/p>\n<\/blockquote>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"cHL_MC\"><span class=\"ez-toc-section\" id=\"Klassisches_Hodgkin-Lymphom_cHL_%E2%80%93_gemischte_Zellularitat_MC\"><\/span><strong>Linfoma de Hodgkin cl\u00e1ssico (cHL) - celularidade mista (MC)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>linfoma de Hodgkin cl\u00e1ssico (cHL), celularidade mista (MC)<\/strong>, \u00e9 um subtipo histol\u00f3gico de cHL, que \u00e9 aproximadamente&nbsp;<strong>25 % de casos<\/strong>&nbsp;e \u00e9 particularmente frequente em doentes com mais de 50 anos e em pessoas seropositivas. Os homens s\u00e3o mais frequentemente afectados do que as mulheres.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild_und_morphologische_Merkmale-4\"><\/span><strong>Quadro cl\u00ednico e carater\u00edsticas morfol\u00f3gicas<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cl\u00ednica<\/strong><br>Infesta\u00e7\u00e3o favorecida&nbsp;<strong>Regi\u00f5es de g\u00e2nglios linf\u00e1ticos cervicais e abdominais<\/strong><br>Em compara\u00e7\u00e3o com outros subtipos de LCC, o tipo misto \u00e9 diagnosticado mais frequentemente numa&nbsp;<strong>fase avan\u00e7ada<\/strong>&nbsp;descoberto e apresenta frequentes&nbsp;<strong>B-sintom\u00e1ticos<\/strong>&nbsp;(febre, suores noturnos, perda de peso &gt;10 % num per\u00edodo de 6 meses)<\/li>\n\n\n\n<li><strong>Morfol\u00f3gico<\/strong><br>- Caracterizado por um&nbsp;<strong>Infiltrado celular misto<\/strong>&nbsp;de c\u00e9lulas de Hodgkin e Reed-Sternberg (c\u00e9lulas H-RS), linf\u00f3citos, histi\u00f3citos, granul\u00f3citos (especialmente eosin\u00f3filos) e fibrose fibrilar fina<br>- As c\u00e9lulas H-RS s\u00e3o&nbsp;<strong>multinucleadas (c\u00e9lulas de Reed-Sternberg)<\/strong>&nbsp;ou mononucleares, com&nbsp;<strong>nucl\u00e9olos proeminentes (\u201ec\u00e9lulas em olho de coruja\u201c)<\/strong>&nbsp;e citoplasma bas\u00f3filo<br>- As c\u00e9lulas tumorais constituem apenas cerca de&nbsp;<strong>0,1-10 %<\/strong>&nbsp;da massa celular total; o resto \u00e9 constitu\u00eddo por um infiltrado inflamat\u00f3rio reativo<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnose_und_-methodik-2\"><\/span><strong>Diagn\u00f3stico diferencial e metodologia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial \u00e9 crucial, uma vez que o LHCC deve ser diferenciado pelo seu padr\u00e3o bif\u00e1sico carater\u00edstico (poucas c\u00e9lulas tumorais, forte infiltrado reativo) e imunofen\u00f3tipos espec\u00edficos.&nbsp;<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Diagn\u00f3sticos diferenciais importantes<\/strong><br>- <strong>Linfoma folicular (FL)<\/strong><br>Prolifera\u00e7\u00e3o neopl\u00e1sica de centr\u00f3citos\/centroblastos com arquitetura t\u00edpica de centro germinal, CD10+, bcl-2+, t(14;18)<br>- <strong>Linfoma difuso de grandes c\u00e9lulas B (DLBCL)<\/strong>Infiltra\u00e7\u00e3o difusa de c\u00e9lulas B grandes e transformadas, CD20+, BCL6+, MUM1+, mais frequentemente com sintomas B e crescimento r\u00e1pido<br>- <strong>Leucemia linfoc\u00edtica cr\u00f3nica (LLC)<\/strong>Linfadenopatia perif\u00e9rica, envolvimento da medula \u00f3ssea, CD5+, CD23+, CD20 (fraco), CD10-<br>- <strong>Linfoma de c\u00e9lulas do manto (LCM)<\/strong>CD5+, CD23-, CD10-, t(11;14), maioritariamente avan\u00e7ado no momento do diagn\u00f3stico, mau progn\u00f3stico<br>- <strong>Mieloma m\u00faltiplo<\/strong>Dor \u00f3ssea, fracturas patol\u00f3gicas, infiltra\u00e7\u00e3o de c\u00e9lulas plasm\u00e1ticas na medula \u00f3ssea, anemia, hipercalcemia<br>- <strong>Linfadenopatia reactiva<\/strong>Sem prolifera\u00e7\u00e3o clonal, tipicamente ap\u00f3s infec\u00e7\u00f5es, com arquitetura normal e aus\u00eancia de c\u00e9lulas H-RS<\/li>\n\n\n\n<li><strong>Metodologia de diagn\u00f3stico<\/strong><br>- <strong>Histologia<\/strong><br>Exame microsc\u00f3pico da prepara\u00e7\u00e3o do g\u00e2nglio linf\u00e1tico com dete\u00e7\u00e3o de c\u00e9lulas H-RS e infiltrado reativo<br>- <strong>Imunohistoqu\u00edmica<\/strong><br><strong>As c\u00e9lulas H-RS s\u00e3o positivas para CD30, CD15, MUM1, PD-L1<\/strong>&nbsp;e maioritariamente negativo para CD45, CD20 (positivo em cerca de 20 %), cadeia J e BOB.1\/Oct2 (negativo no LH cl\u00e1ssico)<br>- <strong>Patologia molecular<\/strong><br>Dete\u00e7\u00e3o de neoplasia clonal de c\u00e9lulas B (por exemplo, por PCR do gene da imunoglobulina, muta\u00e7\u00f5es)<br>- <strong>Imagiologia<\/strong><br>TC\/RM para estadiamento (classifica\u00e7\u00e3o de Ann Arbor), PET-CT para planeamento e monitoriza\u00e7\u00e3o da terapia<br>- <strong>Bi\u00f3psia da medula \u00f3ssea<\/strong><br>Em caso de sintomas B ou de est\u00e1dio avan\u00e7ado, para excluir o envolvimento da medula \u00f3ssea<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie_und_Prognose-7\"><\/span><strong>Terapia e progn\u00f3stico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Princ\u00edpio da terapia<\/strong><br><strong>Poliquimioterapia adaptada \u00e0 fase<\/strong>&nbsp;(por exemplo, ABVD: doxorrubicina, bleomicina, vinblastina, dacarbazina) em combina\u00e7\u00e3o com&nbsp;<strong>Radioterapia<\/strong>&nbsp;Para infesta\u00e7\u00f5es localizadas (fases I-II)<\/li>\n\n\n\n<li><strong>Previs\u00e3o<\/strong><br>Conseguir com terapias modernas&nbsp;<strong>mais de 80 % dos doentes alcan\u00e7am uma cura a longo prazo<\/strong><br>A taxa de sobreviv\u00eancia a 5 anos situa-se entre&nbsp;<strong>75 % e 99 %<\/strong>, em fun\u00e7\u00e3o do est\u00e1dio e dos factores de risco<\/li>\n\n\n\n<li><strong>Factores de progn\u00f3stico<\/strong><br>B sintomas, LDH elevada, idade &gt;50 anos, extens\u00e3o da doen\u00e7a (est\u00e1dio IV), n\u00famero de regi\u00f5es de g\u00e2nglios linf\u00e1ticos afectadas<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O linfoma de Hodgkin cl\u00e1ssico, de celularidade mista, \u00e9 um&nbsp;<strong>Doen\u00e7a bem trat\u00e1vel mas complexa<\/strong>, cujo diagn\u00f3stico e terap\u00eautica se baseiam numa&nbsp;<strong>abordagem multimodal e individualizada<\/strong>&nbsp;baseado.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"cHL_LR\"><span class=\"ez-toc-section\" id=\"Klassisches_Hodgkin-Lymphom_%E2%80%93_lymphozytenreicher_Typ_cHL_LR\"><\/span>Linfoma de Hodgkin cl\u00e1ssico - tipo rico em linf\u00f3citos (cHL, LR)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>Linfoma de Hodgkin cl\u00e1ssico rico em linf\u00f3citos (cHL, LR)<\/strong>&nbsp;\u00e9 uma variante histol\u00f3gica rara do linfoma de Hodgkin cl\u00e1ssico, que pode causar cerca de&nbsp;<strong>4 %<\/strong>&nbsp;de todos os casos.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Atrav\u00e9s de um&nbsp;<strong>Ambiente dominante rico em linf\u00f3citos<\/strong>&nbsp;caracterizado por apenas algumas c\u00e9lulas de Hodgkin e Reed-Sternberg (c\u00e9lulas H-RS), que s\u00e3o tipicamente&nbsp;<strong>CD30- e CD15-positivo<\/strong>&nbsp;s\u00e3o.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">As c\u00e9lulas tumorais tamb\u00e9m transportam frequentemente&nbsp;<strong>CD20<\/strong>&nbsp;e&nbsp;<strong>CD23<\/strong>, mas s\u00e3o&nbsp;<strong>CD30-negativo<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A doen\u00e7a ocorre mais frequentemente em&nbsp;<strong>doentes do sexo masculino com cerca de 30 anos<\/strong>&nbsp;e tem um&nbsp;<strong>Previs\u00e3o muito boa<\/strong>&nbsp;sobre.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild_und_morphologische_Merkmale-5\"><\/span>Quadro cl\u00ednico e carater\u00edsticas morfol\u00f3gicas<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Imagem cl\u00ednica<\/strong><br>O tipo LR manifesta-se normalmente como&nbsp;<strong>Infesta\u00e7\u00e3o dos g\u00e2nglios linf\u00e1ticos perif\u00e9ricos<\/strong>, frequentemente no&nbsp;<strong>Regi\u00e3o cervical ou axilar<\/strong><br>Os doentes apresentam frequentemente&nbsp;<strong>incha\u00e7o indolor dos g\u00e2nglios linf\u00e1ticos<\/strong>, que persistem durante semanas ou meses.<br><strong>Sintomas B<\/strong>&nbsp;(febre, suores noturnos, perda de peso) s\u00e3o menos comuns do que noutros subtipos.&nbsp;<\/li>\n\n\n\n<li><strong>Morfol\u00f3gico<\/strong><br>A imagem histol\u00f3gica mostra uma&nbsp;<strong>Infiltrado rico em linf\u00f3citos<\/strong>&nbsp;(predominantemente linf\u00f3citos T) nas zonas marginal e do manto dos fol\u00edculos linf\u00e1ticos<br>Caracteriza-se por uma&nbsp;<strong>fibrose difusa<\/strong>&nbsp;e um pequeno n\u00famero de c\u00e9lulas H-RS<br>O ambiente \u00e9 constitu\u00eddo por uma mistura de linf\u00f3citos, histi\u00f3citos e granul\u00f3citos<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_-methodik-10\"><\/span>Diagn\u00f3stico diferencial e metodologia<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial \u00e9 crucial, uma vez que o tipo LR pode ser confundido morfol\u00f3gica e imunofenot\u00edpicamente com outros linfomas:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Linfoma agressivo de grandes c\u00e9lulas B rico em histi\u00f3citos de c\u00e9lulas T (TCHRBCL)<\/strong><br>Este linfoma n\u00e3o-Hodgkin agressivo pode ter carater\u00edsticas morfol\u00f3gicas semelhantes, em particular um ambiente linfoc\u00edtico rico<br>Em termos de diagn\u00f3stico diferencial, \u00e9 crucial que o TCHRBCL&nbsp;<strong>CD20-positivo<\/strong>&nbsp;\u00e9, mas&nbsp;<strong>CD30-negativo<\/strong>&nbsp;e&nbsp;<strong>CD15-negativo<\/strong><br>As c\u00e9lulas tumorais s\u00e3o&nbsp;<strong>MUM1-positivo<\/strong>&nbsp;e apresentam uma elevada taxa de prolifera\u00e7\u00e3o<\/li>\n\n\n\n<li><strong>Prolifera\u00e7\u00e3o reactiva dos centros germinais (PTKZ)<\/strong><br>Estas podem ser irritadas por um ambiente rico em linf\u00f3citos e ocasionalmente por c\u00e9lulas do tipo H-RS<br>Os crit\u00e9rios de diferencia\u00e7\u00e3o s\u00e3o os seguintes&nbsp;<strong>Aus\u00eancia de c\u00e9lulas H-RS positivas para CD30 e CD15<\/strong>&nbsp;e o&nbsp;<strong>marcador positivo de c\u00e9lulas B<\/strong>&nbsp;(CD20, CD79a, CD45) nas c\u00e9lulas reactivas<br>O&nbsp;<strong>Negatividade do EBV<\/strong>&nbsp;tamb\u00e9m \u00e9 t\u00edpico<\/li>\n\n\n\n<li><strong>Linfoma de Hodgkin nodular com predomin\u00e2ncia de linf\u00f3citos (NLPHL)<\/strong><br>Embora o NLPHL tamb\u00e9m apresente um ambiente rico em linf\u00f3citos, as c\u00e9lulas tumorais s\u00e3o&nbsp;<strong>CD20-positivo<\/strong>,&nbsp;<strong>CD30-negativo<\/strong>&nbsp;e&nbsp;<strong>CD15-negativo<\/strong><br>As c\u00e9lulas s\u00e3o&nbsp;<strong>EBV-negativo<\/strong>&nbsp;e apresentam uma carater\u00edstica&nbsp;<strong>Predomin\u00e2ncia de linf\u00f3citos<\/strong>&nbsp;com pequenos linf\u00f3citos e c\u00e9lulas epitelioides<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial requer um&nbsp;<strong>An\u00e1lise histol\u00f3gica e imunofenot\u00edpica cuidadosa<\/strong>, para diferencia\u00e7\u00e3o com linfomas agressivos como o TCHRBCL ou prolifera\u00e7\u00f5es reactivas.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-33\"><\/span>Terapia<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Como o tipo de LR \u00e9 um&nbsp;<strong>Previs\u00e3o muito boa<\/strong>&nbsp;a&nbsp;<strong>Terapia adaptada ao risco<\/strong>&nbsp;aplicado.<br>Os doentes com est\u00e1dios iniciais (I-II) recebem frequentemente&nbsp;<strong>quimioterapias curtas<\/strong>&nbsp;(por exemplo, ABVD) em combina\u00e7\u00e3o com&nbsp;<strong>determinada irradia\u00e7\u00e3o<\/strong><br>Para est\u00e1dios avan\u00e7ados (III-IV), um&nbsp;<strong>quimioterapia mais intensiva<\/strong>&nbsp;(por exemplo, BEACOPP), mas com requisitos de irradia\u00e7\u00e3o mais baixos<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-32\"><\/span>Previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>A taxa de sobreviv\u00eancia a 5 anos \u00e9 superior a 90 %<\/strong>.<br>A previs\u00e3o favor\u00e1vel deve-se ao facto de&nbsp;<strong>Elevada sensibilidade \u00e0 quimioterapia e \u00e0 radioterapia<\/strong>&nbsp;atribu\u00edvel.<br>No entanto, as complica\u00e7\u00f5es tardias (por exemplo, tumores secund\u00e1rios, doen\u00e7as cardiovasculares) s\u00e3o poss\u00edveis em doentes mais jovens e requerem um acompanhamento cuidadoso.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"cHL\"><span class=\"ez-toc-section\" id=\"Klassisches_lymphozytenarmes_Hodgkin-Lymphom_cHL\"><\/span><strong>Linfoma de Hodgkin cl\u00e1ssico pobre em linf\u00f3citos (cHL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O <strong>Linfoma de Hodgkin cl\u00e1ssico pobre em linf\u00f3citos (cHL)<\/strong>&nbsp;\u00e9 uma forma rara de linfoma de Hodgkin que afecta cerca de&nbsp;<strong>1 % de casos<\/strong>&nbsp;e especialmente com&nbsp;<strong>doentes idosos<\/strong>&nbsp;ocorre.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Caracteriza-se por uma&nbsp;<strong>Infiltrado difuso e bl\u00e1stico<\/strong>&nbsp;com&nbsp;<strong>poucos linf\u00f3citos<\/strong>&nbsp;e&nbsp;<strong>c\u00e9lulas de Hodgkin e Reed-Sternberg at\u00edpicas (c\u00e9lulas H-RS)<\/strong>&nbsp;que s\u00e3o frequentemente acompanhadas por mitoses e necrose.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">O exame histol\u00f3gico revela uma&nbsp;<strong>infiltra\u00e7\u00e3o difusa de c\u00e9lulas HRS<\/strong>&nbsp;com apenas uma rea\u00e7\u00e3o acompanhante n\u00e3o neopl\u00e1sica esparsa, resultando numa&nbsp;<strong>imagem sarcomatosa<\/strong>&nbsp;pode levar.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild_und_morphologische_Merkmale-6\"><\/span>Quadro cl\u00ednico e carater\u00edsticas morfol\u00f3gicas<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Localiza\u00e7\u00e3o prim\u00e1ria<\/strong><br>Frequentemente&nbsp;<strong>envolvimento dos g\u00e2nglios linf\u00e1ticos abdominais<\/strong>, especialmente na zona do mesent\u00e9rio ou retroperitonealmente<\/li>\n\n\n\n<li><strong>Sintomas<\/strong><br>Tipicamente&nbsp;<strong>Sintomas B<\/strong>&nbsp;(febre, suores noturnos, perda de peso n\u00e3o intencional &gt;10 % em 6 meses), que ocorrem mais frequentemente neste subtipo<\/li>\n\n\n\n<li><strong>Idade<\/strong><br>Prefere pacientes no&nbsp;<strong>idade avan\u00e7ada<\/strong>&nbsp;(maioritariamente &gt;60 anos), com uma&nbsp;<strong>Prefer\u00eancia masculina<\/strong><\/li>\n\n\n\n<li><strong>Morfologia<\/strong><br>As c\u00e9lulas H-RS s\u00e3o&nbsp;<strong>pleom\u00f3rfico<\/strong>, com n\u00facleos grandes e granulares e nucl\u00e9olos proeminentes; os linf\u00f3citos est\u00e3o minimamente presentes<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_-methodik-11\"><\/span>Diagn\u00f3stico diferencial e metodologia<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>linfoma de Hodgkin cl\u00e1ssico pobre em linf\u00f3citos (cHL)<\/strong>&nbsp;deve ser diferenciada, nomeadamente, das seguintes doen\u00e7as:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Linfoma anapl\u00e1sico de grandes c\u00e9lulas (ALK-negativo)<\/strong><br>Este diagn\u00f3stico diferencial \u00e9 particularmente importante, uma vez que ambas as doen\u00e7as t\u00eam carater\u00edsticas morfol\u00f3gicas e imunofenot\u00edpicas semelhantes (por exemplo, CD30+, CD15+)<br><strong>Imunohistoqu\u00edmica<\/strong>&nbsp;(CD20-, CD30+, CD15+, ALK-) e&nbsp;<strong>An\u00e1lises biol\u00f3gicas moleculares<\/strong>&nbsp;(por exemplo.&nbsp;&nbsp;<em>ALK<\/em>-de g\u00e9nero) s\u00e3o cruciais para diferenciar<\/li>\n\n\n\n<li><strong>Altera\u00e7\u00f5es reactivas dos g\u00e2nglios linf\u00e1ticos<\/strong>&nbsp;(por exemplo, no caso de infec\u00e7\u00f5es ou doen\u00e7as auto-imunes)<br>Devido \u00e0 falta de popula\u00e7\u00e3o de c\u00e9lulas clonais e de c\u00e9lulas H-RS<\/li>\n\n\n\n<li><strong>Linfoma agressivo de c\u00e9lulas B (por exemplo, linfoma de grandes c\u00e9lulas B rico em histi\u00f3citos de c\u00e9lulas T, TCHRBCL)<\/strong><br>Diferencia\u00e7\u00e3o atrav\u00e9s de&nbsp;<strong>Positividade CD20<\/strong>&nbsp;(em TCHRBCL),&nbsp;<strong>Positividade CD30<\/strong>&nbsp;e&nbsp;<strong>Negatividade CD15<\/strong>&nbsp;em TCHRBCL<br>Em contraste com o cHL, a estrutura celular H-RS n\u00e3o \u00e9 t\u00edpica do TCHRBCL<\/li>\n\n\n\n<li><strong>Doen\u00e7as associadas ao EBV<\/strong>, em particular&nbsp;<strong>\u00dalcera mucocut\u00e2nea EBV-positiva<\/strong>, uma vez que as c\u00e9lulas CD30+ e CD15+ tamb\u00e9m podem ocorrer aqui<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostik-7\"><\/span>Diagn\u00f3stico<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Diagn\u00f3stico histol\u00f3gico<\/strong><br>S\u00f3 atrav\u00e9s de&nbsp;<strong>Bi\u00f3psia de g\u00e2nglios linf\u00e1ticos<\/strong>&nbsp;com&nbsp;<strong>g\u00e2nglio linf\u00e1tico inteiro<\/strong>&nbsp;poss\u00edvel<br><strong>Aspira\u00e7\u00e3o por agulha fina (citologia)<\/strong>&nbsp;\u00e9 insuficiente!<\/li>\n\n\n\n<li><strong>Imunohistoqu\u00edmica<\/strong><br><strong>CD30+<\/strong>,&nbsp;<strong>CD15+<\/strong>,&nbsp;<strong>CD20-\/\u00b1<\/strong>,&nbsp;<strong>CD45-<\/strong>,&nbsp;<strong>PD-L1+<\/strong>,&nbsp;<strong>MUM1+<\/strong><br><strong>Positividade ao EBV<\/strong>&nbsp;pode ser vari\u00e1vel<\/li>\n\n\n\n<li><strong>Imagiologia<\/strong><br><strong>PET-CT<\/strong>&nbsp;para estadiamento e planeamento do tratamento<br><strong>TC t\u00f3rax\/abd\u00f3men<\/strong>&nbsp;com agente de contraste<\/li>\n\n\n\n<li><strong>Encena\u00e7\u00e3o<\/strong><br>Depois de&nbsp;<strong>classifica\u00e7\u00e3o de Ann Arbor modificada<\/strong>&nbsp;(Fase I-IV)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-34\"><\/span>Terapia<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Princ\u00edpio da terapia<\/strong><br><strong>Poliquimioterapia<\/strong>&nbsp;(por exemplo.&nbsp;&nbsp;<strong>BEACOPP<\/strong>-protocolo) com ou sem&nbsp;<strong>Irradia\u00e7\u00e3o<\/strong>.&nbsp;<\/li>\n\n\n\n<li><strong>Terapia adaptada ao risco<\/strong><br>Devido ao mau progn\u00f3stico, este subtipo \u00e9 frequentemente tratado com&nbsp;<strong>quimioterapia intensiva<\/strong>&nbsp;recomendado<\/li>\n\n\n\n<li><strong>Novas terapias<\/strong><br>Em caso de recidiva ou de fracasso do tratamento:&nbsp;<strong>Terapias com anticorpos<\/strong>&nbsp;(por exemplo.&nbsp;&nbsp;<strong>Brentuximab vedotina<\/strong>, um anticorpo anti-CD30),&nbsp;<strong>Inibidores do ponto de controlo<\/strong>&nbsp;(por exemplo.&nbsp;<strong>Pembrolizumab<\/strong>, Anti-PD-1)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-33\"><\/span>Previs\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Pior previs\u00e3o<\/strong>&nbsp;de todos os subtipos de linfoma de Hodgkin<\/li>\n\n\n\n<li><strong>Taxa de sobreviv\u00eancia a 5 anos<\/strong><br>Significativamente menor em compara\u00e7\u00e3o com outros subtipos (abaixo de 75 %, dependendo do estadiamento e da terapia)<\/li>\n\n\n\n<li><strong>Risco de recorr\u00eancia<\/strong><br>\u00e9 elevado, pelo que&nbsp;<strong>Cuidados posteriores intensivos<\/strong>&nbsp;com PET-CT regular e controlos cl\u00ednicos necess\u00e1rios<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"NLPHL\"><span class=\"ez-toc-section\" id=\"Nodulares_lymphozytenpradominantes_Hodgkin-Lymphom_NLPHL-2\"><\/span><strong>Linfoma de Hodgkin nodular com predomin\u00e2ncia de linf\u00f3citos (NLPHL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O <strong>Linfoma de Hodgkin nodular com predomin\u00e2ncia de linf\u00f3citos (NLPHL)<\/strong>&nbsp;\u00e9 um subtipo raro de linfoma de Hodgkin, que pode causar cerca de&nbsp;<strong>5-10 % de todos os casos de linfoma de Hodgkin<\/strong>&nbsp;faz a diferen\u00e7a.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Caracteriza-se por uma&nbsp;<strong>Previs\u00e3o favor\u00e1vel<\/strong>, a&nbsp;<strong>Tend\u00eancia para um envolvimento limitado dos g\u00e2nglios linf\u00e1ticos<\/strong>&nbsp;(especialmente no pesco\u00e7o, axila e virilha) e uma&nbsp;<strong>Baixa frequ\u00eancia de sintomas B<\/strong>&nbsp;(febre, suores noturnos, perda de peso).&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild_und_morphologische_Merkmale-7\"><\/span><strong>Quadro cl\u00ednico e carater\u00edsticas morfol\u00f3gicas<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Idade<\/strong><br>Normalmente come\u00e7a antes dos 40 anos de idade, com uma propor\u00e7\u00e3o de homens de cerca de&nbsp;<strong>3:1<\/strong><\/li>\n\n\n\n<li><strong>Imagem cl\u00ednica<\/strong><br>Principalmente&nbsp;<strong>Doen\u00e7a limitada em est\u00e1dio I ou II (&gt;80 % dos casos)<\/strong>.<br>O envolvimento do mediastino \u00e9 raro<br>As manifesta\u00e7\u00f5es extranodais s\u00f3 ocorrem em&nbsp;<strong>10-15 % de casos no ba\u00e7o<\/strong>, menos frequentemente no f\u00edgado, na medula \u00f3ssea ou nos pulm\u00f5es<\/li>\n\n\n\n<li><strong>Morfologia<\/strong><br>Histologicamente caracterizado por&nbsp;<strong>c\u00e9lulas com predomin\u00e2ncia de linf\u00f3citos (LP)<\/strong>que&nbsp;<strong>CD20-positivo<\/strong>,&nbsp;<strong>CD15-negativo<\/strong>&nbsp;e&nbsp;<strong>CD30-negativo<\/strong>&nbsp;s\u00e3o.<br>Estas c\u00e9lulas s\u00e3o c\u00e9lulas B monoclonais com origem no centro germinal.<br>Em contraste com o linfoma de Hodgkin cl\u00e1ssico, as c\u00e9lulas t\u00edpicas de Hodgkin e Reed-Sternberg est\u00e3o ausentes.<br>As c\u00e9lulas tumorais est\u00e3o localizadas em&nbsp;<strong>estruturas nodulares<\/strong>, frequentemente rodeado por um envelope denso de linf\u00f3citos.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnosen_und_Differenzialmethodik\"><\/span><strong>Diagn\u00f3sticos diferenciais e metodologia diferencial<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O diagn\u00f3stico diferencial \u00e9 crucial, uma vez que o NLPHL se sobrep\u00f5e morfol\u00f3gica e imunofenot\u00edpicamente a outros linfomas.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Os diagn\u00f3sticos diferenciais mais importantes s\u00e3o<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Linfoma de Hodgkin cl\u00e1ssico rico em linf\u00f3citos (cHL, tipo rico em linf\u00f3citos)<\/strong><br>- <strong>Diferen\u00e7a<\/strong>Embora ambos tenham um ambiente rico em linf\u00f3citos, as c\u00e9lulas tumorais no LNHc&nbsp;<strong>CD20-negativo<\/strong>,&nbsp;<strong>CD15-positivo<\/strong>&nbsp;e&nbsp;<strong>CD30-positivo<\/strong>, em contraste com o NLPHL<br>- <strong>Diferencia\u00e7\u00e3o<\/strong>Imunofen\u00f3tipo: o imunofen\u00f3tipo \u00e9 decisivo<\/li>\n\n\n\n<li><strong>Transforma\u00e7\u00e3o progressiva dos centros germinais (PTC)<\/strong><br>- <strong>Diferen\u00e7a<\/strong>PTC \u00e9 um&nbsp;<strong>pr\u00e9-maligno, n\u00e3o clonal<\/strong>&nbsp;Altera\u00e7\u00e3o que parece muito semelhante do ponto de vista histol\u00f3gico<br>- <strong>Diferencia\u00e7\u00e3o<\/strong>Clonalidade (por exemplo, atrav\u00e9s de&nbsp;<strong>PCR para genes de imunoglobulinas<\/strong>) mostra uma prolifera\u00e7\u00e3o monoclonal de c\u00e9lulas B no NLPHL, mas uma prolifera\u00e7\u00e3o policlonal no PTC.<\/li>\n\n\n\n<li><strong>Linfoma de grandes c\u00e9lulas B rico em c\u00e9lulas T\/histi\u00f3citos (THRLBCL)<\/strong><br>- <strong>Diferen\u00e7a<\/strong>THRLBCL mostra&nbsp;<strong>Comportamento cl\u00ednico agressivo<\/strong>, estado avan\u00e7ado e mau progn\u00f3stico<br>- <strong>Diferencia\u00e7\u00e3o<\/strong>Padr\u00f5es histologicamente semelhantes (difuso, at\u00edpico), mas&nbsp;<strong>As c\u00e9lulas T dominam<\/strong>,&nbsp;<strong>CD20-positivo com c\u00e9lulas B<\/strong>,&nbsp;<strong>Sem c\u00e9lulas LP<\/strong><br>- <strong>Molecular<\/strong>THRLBCL mostra&nbsp;<strong>Rearranjo clonal do recetor de c\u00e9lulas T<\/strong>&nbsp;- em contraste com o NLPHL, que&nbsp;<strong>Rearranjo clonal de c\u00e9lulas B<\/strong>&nbsp;tem<\/li>\n\n\n\n<li><strong>Linfoma folicular (FL)<\/strong><br>- <strong>Diferen\u00e7a<\/strong>FL \u00e9 um&nbsp;<strong>Linfoma n\u00e3o-Hodgkin<\/strong>, com&nbsp;<strong>prolifera\u00e7\u00e3o folicular<\/strong>&nbsp;e&nbsp;<strong>C\u00e9lulas B<\/strong>que&nbsp;<strong>CD20-positivo<\/strong>,&nbsp;<strong>CD10-positivo<\/strong>&nbsp;s\u00e3o<br>- <strong>Diferencia\u00e7\u00e3o<\/strong>Sem c\u00e9lulas LP, sem sobreposi\u00e7\u00e3o de c\u00e9lulas T-histi\u00f3citos.&nbsp;<strong>CD21-positivo<\/strong>&nbsp;nos fol\u00edculos (em contraste com a NLPHL)<\/li>\n\n\n\n<li><strong>Linfoma angioimunobl\u00e1stico de c\u00e9lulas T (AITL)<\/strong><br>- <strong>Diferen\u00e7a<\/strong>Espect\u00e1culos&nbsp;<strong>Rearranjo clonal de c\u00e9lulas T<\/strong>,&nbsp;<strong>CD4-positivo<\/strong>,&nbsp;<strong>CD10-negativo<\/strong>,&nbsp;<strong>CD21-negativo<\/strong><br>- <strong>Diferencia\u00e7\u00e3o<\/strong>:&nbsp;<strong>Densidade vascular e infiltrado de c\u00e9lulas T<\/strong>&nbsp;(elevado para AITL, baixo para NLPHL) e&nbsp;<strong>CD20-positivo com c\u00e9lulas T<\/strong>&nbsp;no AITL<\/li>\n\n\n\n<li><strong>Linfoma folicular de c\u00e9lulas T (FTCL)<\/strong><br>- <strong>Diferen\u00e7a<\/strong>:&nbsp;<strong>Rearranjo clonal de c\u00e9lulas T<\/strong>,&nbsp;<strong>CD4-positivo<\/strong>,&nbsp;<strong>CD8-negativo<\/strong>,&nbsp;<strong>CD20-negativo<\/strong><br>- <strong>Diferencia\u00e7\u00e3o<\/strong>: Dete\u00e7\u00e3o molecular de um&nbsp;<strong>Rearranjo do recetor de c\u00e9lulas T<\/strong><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostik-8\"><\/span><strong>Diagn\u00f3stico<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Bi\u00f3psia de g\u00e2nglios linf\u00e1ticos<\/strong>&nbsp;com an\u00e1lise histol\u00f3gica e imunofenot\u00edpica<\/li>\n\n\n\n<li><strong>Marcador central<\/strong><br><strong>CD20+<\/strong>,&nbsp;<strong>CD15-<\/strong>,&nbsp;<strong>CD30-<\/strong>,&nbsp;<strong>PAX5+<\/strong>,&nbsp;<strong>BCL6+<\/strong>,&nbsp;<strong>CD45+<\/strong>.&nbsp;<\/li>\n\n\n\n<li><strong>Biologia molecular<\/strong><br><strong>PCR para genes de imunoglobulinas<\/strong>&nbsp;para assegurar a clonalidade das c\u00e9lulas B<\/li>\n\n\n\n<li><strong>Encena\u00e7\u00e3o<\/strong><br><strong>Sistema de prepara\u00e7\u00e3o Cotswold<\/strong>&nbsp;para determinar o grau de gravidade e de propaga\u00e7\u00e3o<\/li>\n\n\n\n<li><strong>Bi\u00f3psia para dete\u00e7\u00e3o de recidiva<\/strong><br><strong>Obrigat\u00f3rio<\/strong>, como&nbsp;<strong>Transforma\u00e7\u00e3o em linfoma difuso de grandes c\u00e9lulas B (DLBCL)<\/strong>&nbsp;aproximadamente&nbsp;<strong>10 % de casos no prazo de 10 anos<\/strong>&nbsp;apar\u00eancia<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-35\"><\/span><strong>Terapia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Est\u00e1dio IA sem factores de risco<\/strong><br>- <strong>Irradia\u00e7\u00e3o da zona afetada (IFRT)<\/strong>&nbsp;com 30-36 Gy&nbsp;<\/li>\n\n\n\n<li><strong>Est\u00e1dio IA com factores de risco ou est\u00e1dio superior (II-IV)<\/strong><br>- <strong>Semelhante ao HL cl\u00e1ssico<\/strong>:&nbsp;<strong>Quimioterapia (por exemplo, ABVD)<\/strong>&nbsp;ou&nbsp;<strong>Terapia combinada<\/strong><br>- <strong>Protocolos de terapia de linfoma n\u00e3o-Hodgkin de c\u00e9lulas B (B-NHL)<\/strong>&nbsp;tamb\u00e9m s\u00e3o eficazes<\/li>\n\n\n\n<li><strong>Recorr\u00eancia<\/strong><br>- <strong>Rituximab (anticorpo anti-CD20)<\/strong>&nbsp;\u00e9&nbsp;<strong>Muito eficaz<\/strong><br>- Quimioterapia de alta dose com&nbsp;<strong>transplante aut\u00f3logo de c\u00e9lulas estaminais<\/strong>&nbsp;apenas para&nbsp;<strong>poucos casos<\/strong>&nbsp;necess\u00e1rio<\/li>\n\n\n\n<li><strong>Novas abordagens<\/strong><br>Verificar estudos cl\u00ednicos&nbsp;<strong>Rituximab + quimioterapia<\/strong>&nbsp;na primeira linha, especialmente nas fases superiores<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-34\"><\/span><strong>Previs\u00e3o<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Muito bom<\/strong><br>- <strong>Taxa de sobreviv\u00eancia a 10 anos &gt;90 %<\/strong>&nbsp;para doen\u00e7a limitada<br>- <strong>A terap\u00eautica de primeira linha conduz \u00e0 remiss\u00e3o em 90-100 %<\/strong><\/li>\n\n\n\n<li><strong>Taxa de recorr\u00eancia<\/strong><br><strong>10-15 %<\/strong>, principalmente&nbsp;<strong>3-6 anos ap\u00f3s o diagn\u00f3stico<\/strong><\/li>\n\n\n\n<li><strong>Consequ\u00eancias a longo prazo<\/strong><br>- <strong>Doen\u00e7as malignas secund\u00e1rias<\/strong><br>\u2013 \u2013 <strong>Linfoma difuso de grandes c\u00e9lulas B (DLBCL)<\/strong>:&nbsp;<strong>25 % Risco ap\u00f3s 20 anos<\/strong><br>\u2013 \u2013 <strong>Carcinomas (pulm\u00e3o, mama, trato gastrointestinal)<\/strong> frequentemente em regi\u00f5es irradiadas<br>\u2013 \u2013 <strong>Doen\u00e7as cardiopulmonares<\/strong>&nbsp;como resultado de radioterapia<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O&nbsp;<strong>O diagn\u00f3stico diferencial \u00e9 fundamental<\/strong>, especialmente com&nbsp;<strong>THRLBCL, PTC, FL e AITL<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A terapia \u00e9&nbsp;<strong>adaptado \u00e0 fase<\/strong>, com&nbsp;<strong>Radioterapia nas fases iniciais<\/strong>&nbsp;e&nbsp;<strong>Quimioterapia para casos avan\u00e7ados<\/strong>.&nbsp;<strong>Rituximab<\/strong>&nbsp;\u00e9 a terapia de elei\u00e7\u00e3o.<\/p>\n\n\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Standard-Therapeutika_Chemo\"><\/span>Terap\u00eautica padr\u00e3o (quimioterapia)<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">A quimioterapia para os linfomas depende do tipo (linfoma de Hodgkin vs. linfoma n\u00e3o-Hodgkin), do est\u00e1dio e do perfil de risco.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Os efeitos secund\u00e1rios indesej\u00e1veis mais comuns s\u00e3o (ver abaixo os efeitos secund\u00e1rios espec\u00edficos):<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Mielossupress\u00e3o (anemia, neutropenia, trombocitopenia)<\/li>\n\n\n\n<li>N\u00e1useas, v\u00f3mitos, cansa\u00e7o (fadiga)<\/li>\n\n\n\n<li>Queda de cabelo<\/li>\n\n\n\n<li>Imunossupress\u00e3o<\/li>\n\n\n\n<li>Diminui\u00e7\u00e3o da fertilidade (em homens e mulheres)<\/li>\n\n\n\n<li>Tumores secund\u00e1rios (a longo prazo, especialmente com alquilantes e inibidores da topoisomerase II, como o etoposido)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"3-hodgkin-lymphom\"><span class=\"ez-toc-section\" id=\"Hodgkin-Lymphom-2\"><\/span><strong>Linfoma de Hodgkin<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"ABVD\"><\/span>ABVD<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Norma nas fases inicial e avan\u00e7ada:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Bleomicina<\/strong><br>Fibrose pulmonar (dependente da dose), pneumonite (rara mas grave)<\/li>\n\n\n\n<li><strong>Doxorrubicina<\/strong><br>Cardiotoxicidade (dependente da dose), queda de cabelo, n\u00e1useas<\/li>\n\n\n\n<li><strong>Vinblastina<\/strong><br>Neuropatia (perturba\u00e7\u00f5es sensoriais), obstipa\u00e7\u00e3o<\/li>\n\n\n\n<li><strong>Dacarbazina<\/strong><br>N\u00e1useas, fadiga, supressor da mielo.<br>\u2192 Hematotoxicidade inferior \u00e0 do BEACOPP, mas risco pulmonar e card\u00edaco<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"BEACOPP\"><\/span>BEACOPP<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Para risco m\u00e9dio a elevado:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Bleomicina<\/strong><br>Fibrose pulmonar (dependente da dose), pneumonite (rara mas grave)<\/li>\n\n\n\n<li>Adriamicina<\/li>\n\n\n\n<li><strong>vincristina<\/strong> (Oncovin)<br>Neuropatia (formigueiro, pele peluda), obstipa\u00e7\u00e3o<br>\u2192&nbsp;<strong>Maior toxicidade aguda<\/strong>, especialmente hematol\u00f3gicos; aumento do risco de tumores secund\u00e1rios a longo prazo<\/li>\n\n\n\n<li><strong>Prednisolona<\/strong><br><strong>Frequentemente<\/strong>Aumento de peso, aumento do apetite, reten\u00e7\u00e3o de \u00e1gua (edema), redistribui\u00e7\u00e3o do tecido adiposo (obesidade troncular, cara de lua, pesco\u00e7o de touro), aumento do a\u00e7\u00facar no sangue (risco de diabetes), imunossupress\u00e3o (maior suscetibilidade a infec\u00e7\u00f5es), osteoporose, perda muscular, perturba\u00e7\u00f5es do sono.<br><strong>Ocasionalmente<\/strong>Altera\u00e7\u00f5es da pele (pele fina, estrias, acne), problemas oculares (cataratas, glaucoma), tens\u00e3o arterial elevada, problemas gastrointestinais (\u00falceras).&nbsp;<br><strong>Mais raro<\/strong>Altera\u00e7\u00f5es de humor, depress\u00e3o, euforia, estados psic\u00f3ticos, dores de cabe\u00e7a, perturba\u00e7\u00f5es menstruais, impot\u00eancia.&nbsp;<br><strong>Aplica\u00e7\u00e3o a longo prazo<\/strong>Risco de les\u00f5es renais, arteriosclerose prematura, disfun\u00e7\u00e3o adrenal.<\/li>\n\n\n\n<li><strong>Etoposido<\/strong><br>Mielossupress\u00e3o (neutropenia, trombocitopenia), aumento do risco de infe\u00e7\u00e3o<\/li>\n\n\n\n<li><strong>Ciclofosfamida<\/strong><br>Les\u00f5es da bexiga (cistite hemorr\u00e1gica), mielossupressores<\/li>\n\n\n\n<li><strong>Procarbazina<\/strong><br>Mielossupress\u00e3o, toxicidade gastrointestinal, intera\u00e7\u00e3o com inibidores da MAO<\/li>\n\n\n\n<li><strong>vincristina<\/strong><br>Neuropatia (formigueiro, pele peluda), obstipa\u00e7\u00e3o<br>\u2192&nbsp;<strong>Maior toxicidade aguda<\/strong>, especialmente hematol\u00f3gicos; aumento do risco de tumores secund\u00e1rios a longo prazo<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"BrECADD\"><\/span><strong>BrECADD<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Novo padr\u00e3o em est\u00e1dios avan\u00e7ados (18-60 anos)<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Brentuximab vedotina<\/strong><br><strong>Neuropatia perif\u00e9rica<\/strong>&nbsp;(sensorial\/motor), o efeito secund\u00e1rio espec\u00edfico mais comum, em at\u00e9 50 % dos doentes, leva \u00e0 interrup\u00e7\u00e3o da terap\u00eautica em 23 %<br><strong>Polineuropatia desmielinizante<\/strong>, raros mas graves (por exemplo, tipo Guillain-Barr\u00e9).&nbsp;<br><strong>Reac\u00e7\u00f5es de infus\u00e3o e reac\u00e7\u00f5es anafil\u00e1ticas<\/strong> devido ao componente anticorpo.&nbsp;<br>!- <strong>Toxicidade pulmonar<\/strong>, contraindica\u00e7\u00e3o absoluta com&nbsp;<strong>Bleomicina<\/strong>&nbsp;\u2013 <strong>Possibilidade de fibrose pulmonar com risco de vida<\/strong> - !<br><strong>Reac\u00e7\u00f5es cut\u00e2neas raras mas graves<\/strong> - <strong>S\u00edndrome de Stevens-Johnson<\/strong>&nbsp;e necr\u00f3lise epid\u00e9rmica t\u00f3xica<br><strong>Leucoencefalopatia multifocal progressiva (PML)<\/strong> devido \u00e0 reativa\u00e7\u00e3o do v\u00edrus JC, <strong>Potencialmente fatal<\/strong><br><strong>S\u00edndrome de lise tumoral<\/strong> para uma carga tumoral elevada<br><strong>Restri\u00e7\u00e3o da fertilidade<\/strong>, Poss\u00edvel comprometimento da fertilidade masculina - recomenda-se a congela\u00e7\u00e3o de esperma antes de iniciar o tratamento<\/li>\n\n\n\n<li><strong>Etoposido<\/strong><br>Mielossupress\u00e3o (neutropenia, trombocitopenia), aumento do risco de infe\u00e7\u00e3o<\/li>\n\n\n\n<li><strong>Ciclofosfamida<\/strong><br>Les\u00f5es da bexiga (cistite hemorr\u00e1gica), mielossupressores<\/li>\n\n\n\n<li><strong>Doxorrubicina<\/strong><br>Cardiotoxicidade (dependente da dose), queda de cabelo, n\u00e1useas<\/li>\n\n\n\n<li><strong>Dacarbazina<\/strong><br>N\u00e1useas, fadiga, supressor da mielo.<br>\u2192 Hematotoxicidade inferior \u00e0 do BEACOPP, mas risco pulmonar e card\u00edaco<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"3-non-hodgkin-lymphom-nhl\"><span class=\"ez-toc-section\" id=\"Non-Hodgkin-Lymphom_NHL\"><\/span><strong>Linfoma n\u00e3o-Hodgkin (LNH)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"CHOP\"><\/span>CHOP<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Regime de base, frequentemente combinado com <strong>Rituximab<\/strong> (<strong>R-CHOP<\/strong>)<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Ciclofosfamida<\/strong><br>Les\u00f5es da bexiga (cistite hemorr\u00e1gica), mielossupressores<\/li>\n\n\n\n<li><strong>vincristina<\/strong> (Oncovin)<br>Neuropatia (formigueiro, pele peluda), obstipa\u00e7\u00e3o<br>\u2192&nbsp;<strong>Maior toxicidade aguda<\/strong>, especialmente hematol\u00f3gicos; aumento do risco de tumores secund\u00e1rios a longo prazo<\/li>\n\n\n\n<li><strong>Doxorrubicina<\/strong><br>Cardiotoxicidade (dependente da dose), queda de cabelo, n\u00e1useas<\/li>\n\n\n\n<li><strong>Prednisona<\/strong> - A prednisona \u00e9 um&nbsp;<strong>Prodrug<\/strong>&nbsp;e deve ser ativado atrav\u00e9s do f\u00edgado \u2192 a prednisolona \u00e9 prefer\u00edvel em caso de disfun\u00e7\u00e3o hep\u00e1tica.<br><strong>Frequentemente<\/strong>Aumento de peso, aumento do apetite, reten\u00e7\u00e3o de \u00e1gua (edema), redistribui\u00e7\u00e3o do tecido adiposo (obesidade troncular, cara de lua, pesco\u00e7o de touro), aumento do a\u00e7\u00facar no sangue (risco de diabetes), imunossupress\u00e3o (maior suscetibilidade a infec\u00e7\u00f5es), osteoporose, perda muscular, perturba\u00e7\u00f5es do sono.<br><strong>Ocasionalmente<\/strong>Altera\u00e7\u00f5es da pele (pele fina, estrias, acne), problemas oculares (cataratas, glaucoma), tens\u00e3o arterial elevada, problemas gastrointestinais (\u00falceras).&nbsp;<br><strong>Mais raro<\/strong>Altera\u00e7\u00f5es de humor, depress\u00e3o, euforia, estados psic\u00f3ticos, dores de cabe\u00e7a, perturba\u00e7\u00f5es menstruais, impot\u00eancia.&nbsp;<br><strong>Aplica\u00e7\u00e3o a longo prazo<\/strong>Risco de les\u00f5es renais, arteriosclerose prematura, disfun\u00e7\u00e3o adrenal.<br><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"R-Bendamustin\"><\/span><strong>R-Bendamustina<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Alternativa ao R-CHOP, especialmente para doentes mais velhos<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Rituximab<\/strong><br>Reac\u00e7\u00f5es de infus\u00e3o.<br>\u2192 Possibilidade de les\u00f5es graves nos rins e nos nervos<\/li>\n\n\n\n<li><strong>Bendamustina<\/strong><br>Mielossupress\u00e3o, suscetibilidade a infec\u00e7\u00f5es, reac\u00e7\u00f5es cut\u00e2neas<br>Menor risco de queda de cabelo e neuropatia<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"R-DHAP_R-ICE\"><\/span><strong>R-DHAP \/ R-ICE<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Terapias intensivas para a reca\u00edda, antes do transplante de c\u00e9lulas estaminais<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Rituximab<\/strong><br>Reac\u00e7\u00f5es de infus\u00e3o.<br>\u2192 Possibilidade de les\u00f5es graves nos rins e nos nervos<\/li>\n\n\n\n<li><strong>Dexametasona<\/strong><br><strong>Maior risco de osteoporose<\/strong>&nbsp;em compara\u00e7\u00e3o com outros glucocortic\u00f3ides, especialmente devido \u00e0 perda de c\u00e1lcio.&nbsp;<br><strong>Crise do feocromocitoma<\/strong> Raro, mas com risco de vida, com sintomas como tens\u00e3o arterial elevada, dores de cabe\u00e7a, suores e palpita\u00e7\u00f5es no caso de um tumor adrenal desconhecido<br><strong>Reac\u00e7\u00f5es anafil\u00e1cticas graves<\/strong>Raros, mas poss\u00edveis, at\u00e9 insufici\u00eancia circulat\u00f3ria, paragem card\u00edaca ou broncospasmo<br><strong>Efeitos secund\u00e1rios centrais<\/strong> Perturba\u00e7\u00f5es mentais (euforia, intoxica\u00e7\u00e3o, depress\u00e3o), ins\u00f3nia, dores de cabe\u00e7a, raramente crises epil\u00e9pticas ou pseudotumor cerebral (aumento da press\u00e3o intracraniana)<br><strong>Administra\u00e7\u00e3o intravenosa demasiado r\u00e1pida<\/strong> pode provocar parestesia de curta dura\u00e7\u00e3o (formigueiro, ardor), rubor ou irrita\u00e7\u00e3o das veias, pelo que deve ser administrado lentamente (2-3 minutos)<br><strong>Contraindica\u00e7\u00e3o para determinadas infec\u00e7\u00f5es<\/strong> devido ao risco de ativa\u00e7\u00e3o de infec\u00e7\u00f5es latentes (por exemplo, varicela, sarampo, lombriga an\u00e3)<br><strong>Olhos<\/strong> Risco de glaucoma e catarata, especialmente com uso ocular ou prolongado.&nbsp;<br><strong>Inje\u00e7\u00e3o nas articula\u00e7\u00f5es<\/strong> Raramente, rutura do tend\u00e3o ou fratura do corpo vertebral<\/li>\n\n\n\n<li><strong>Citarabina em dose elevada<\/strong> (citarabina)<br>Ataxia, conjuntivite, mielossupress\u00e3o<\/li>\n\n\n\n<li><strong>Platina<\/strong> (Cisplatina)<br><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\" id=\"4-r-ice\"><span class=\"ez-toc-section\" id=\"R-ICE\"><\/span><strong>R-ICE<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Terapias intensivas para a reca\u00edda, antes do transplante de c\u00e9lulas estaminais<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Rituximab<\/strong><br>Reac\u00e7\u00f5es de infus\u00e3o.<br>\u2192 Possibilidade de les\u00f5es graves nos rins e nos nervos<\/li>\n\n\n\n<li><strong>Ifosfamida<\/strong><br>Neurotoxicidade (encefalopatia), les\u00f5es da bexiga urin\u00e1ria (\u00e9 necess\u00e1ria prote\u00e7\u00e3o do mesna)<\/li>\n\n\n\n<li><strong>Carboplatina<\/strong><br>Mielossupress\u00e3o (queda acentuada dos valores sangu\u00edneos)<\/li>\n\n\n\n<li><strong>Etoposido<\/strong><br>Mielossupress\u00e3o, risco de leucemia secund\u00e1ria.<br>\u2192 Menor nefro e ototoxicidade do que a cisplatina, mas maior toxicidade a n\u00edvel neurol\u00f3gico e da bexiga<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"CVP\"><\/span>CVP<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Para formas indolentes, como o linfoma folicular<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Ciclofosfamida<\/strong><br>Les\u00f5es da bexiga (cistite hemorr\u00e1gica), mielossupressores<\/li>\n\n\n\n<li><strong>vincristina<\/strong> (Oncovin)<br>Neuropatia (formigueiro, pele peluda), obstipa\u00e7\u00e3o<br>\u2192&nbsp;<strong>Maior toxicidade aguda<\/strong>, especialmente hematol\u00f3gicos; aumento do risco de tumores secund\u00e1rios a longo prazo<\/li>\n\n\n\n<li><strong>Prednisona<\/strong> - A prednisona \u00e9 um&nbsp;<strong>Prodrug<\/strong>&nbsp;e deve ser ativado atrav\u00e9s do f\u00edgado \u2192 a prednisolona \u00e9 prefer\u00edvel em caso de disfun\u00e7\u00e3o hep\u00e1tica.<br><strong>Frequentemente<\/strong>Aumento de peso, aumento do apetite, reten\u00e7\u00e3o de \u00e1gua (edema), redistribui\u00e7\u00e3o do tecido adiposo (obesidade troncular, cara de lua, pesco\u00e7o de touro), aumento do a\u00e7\u00facar no sangue (risco de diabetes), imunossupress\u00e3o (maior suscetibilidade a infec\u00e7\u00f5es), osteoporose, perda muscular, perturba\u00e7\u00f5es do sono.<br><strong>Ocasionalmente<\/strong>Altera\u00e7\u00f5es da pele (pele fina, estrias, acne), problemas oculares (cataratas, glaucoma), tens\u00e3o arterial elevada, problemas gastrointestinais (\u00falceras).&nbsp;<br><strong>Mais raro<\/strong>Altera\u00e7\u00f5es de humor, depress\u00e3o, euforia, estados psic\u00f3ticos, dores de cabe\u00e7a, perturba\u00e7\u00f5es menstruais, impot\u00eancia.&nbsp;<br><strong>Aplica\u00e7\u00e3o a longo prazo<\/strong>Risco de les\u00f5es renais, arteriosclerose prematura, disfun\u00e7\u00e3o adrenal.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"3-spezielle-formen\"><span class=\"ez-toc-section\" id=\"Spezielle_Formen\"><\/span><strong>Moldes especiais<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Linfoma de c\u00e9lulas do manto<\/strong><br>Frequentemente intensivo com R-DHAP ou R-CHOP, seguido de quimioterapia de alta dose + transplante de c\u00e9lulas estaminais<\/li>\n\n\n\n<li><strong>Linfomas de c\u00e9lulas T<\/strong><br>Regimes baseados em CHOP, possivelmente com etoposido (CHOEP)<a href=\"https:\/\/www.pflege-onkologie.de\/indikationen\/non-hodgkin-lymphome\/therapie\" target=\"_blank\" rel=\"noreferrer noopener\"><\/a><a href=\"https:\/\/www.krebsgesellschaft.de\/onko-internetportal\/basis-informationen-krebs\/krebsarten\/morbus-hodgkin\/therapie.html\" target=\"_blank\" rel=\"noreferrer noopener\"><\/a><\/li>\n<\/ul>\n\n\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Standard-Therapeutika_%E2%80%93_Signalwege\"><\/span>Terap\u00eautica padr\u00e3o - vias de sinaliza\u00e7\u00e3o<a href=\"https:\/\/www.onkopedia.com\/de\/onkopedia\/guidelines\/hodgkin-lymphom\" target=\"_blank\" rel=\"noreferrer noopener\"><\/a><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"9-bendamustin\"><span class=\"ez-toc-section\" id=\"Bendamustin\"><\/span><strong>Bendamustina<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Alquila\u00e7\u00e3o do ADN<\/strong>A bendamustina \u00e9 um&nbsp;<strong>alquilano bifuncional<\/strong>&nbsp;(derivado de \u00f3xido de azoto), que forma grupos alquilo electrof\u00edlicos. Estes ligam-se covalentemente ao&nbsp;<strong>Posi\u00e7\u00e3o N7 da guanina<\/strong>&nbsp;no ADN \u2192 conduz a&nbsp;<strong>liga\u00e7\u00f5es cruzadas de ADN intra e inter-fitas<\/strong><\/li>\n\n\n\n<li>As liga\u00e7\u00f5es cruzadas interferem&nbsp;<strong>Replica\u00e7\u00e3o do ADN<\/strong>,&nbsp;<strong>Transcri\u00e7\u00e3o<\/strong>&nbsp;e&nbsp;<strong>Repara\u00e7\u00e3o<\/strong>&nbsp;\u2192 Quebras da cadeia de ADN (especialmente quebras da cadeia dupla)<\/li>\n\n\n\n<li>Ativa\u00e7\u00e3o de&nbsp;<strong>p53<\/strong>&nbsp;e&nbsp;<strong>Resposta aos danos no ADN<\/strong>&nbsp;\u2192 Paragem do ciclo celular e&nbsp;<strong>Apoptose<\/strong><\/li>\n\n\n\n<li>Inibe a&nbsp;<strong>Via de repara\u00e7\u00e3o das alquiltransferases<\/strong>&nbsp;e, em vez disso, favorece o&nbsp;<strong>Via de repara\u00e7\u00e3o da excis\u00e3o nucleot\u00eddica<\/strong>, o que torna a repara\u00e7\u00e3o mais dif\u00edcil<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Efeito adicional<\/strong>Estrutura do an\u00e1logo da purina \u2192&nbsp;<strong>inibe a s\u00edntese de purinas<\/strong>&nbsp;(propriedades antimetab\u00f3licas).&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Eficaz&nbsp;<strong>Ciclo n\u00e3o espec\u00edfico<\/strong>, tamb\u00e9m contra c\u00e9lulas dormentes.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Mostra atividade em tumores resistentes aos alquilanos, uma vez que a repara\u00e7\u00e3o dos danos no ADN \u00e9 mais lenta e menos eficiente.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Bleomycin\"><\/span>Bleomicina<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Liga-se a&nbsp;<strong>Ferro(II)<\/strong>&nbsp;(Fe\u00b2\u207a) e forma um&nbsp;<strong>Complexo de bleomicina-Fe(II)<\/strong><\/li>\n\n\n\n<li>Este complexo reage com&nbsp;<strong>oxig\u00eanio<\/strong>&nbsp;e formul\u00e1rios&nbsp;<strong>esp\u00e9cies reactivas de oxig\u00e9nio (ROS)<\/strong>&nbsp;como os radicais super\u00f3xido e hidroxilo<\/li>\n\n\n\n<li>A causa dos ERO&nbsp;<strong>Quebras da cadeia de ADN<\/strong>&nbsp;(quebras de cadeia simples e dupla), especialmente em&nbsp;<strong>Sequ\u00eancias ricas em G-C<\/strong><\/li>\n\n\n\n<li>Danos espec\u00edficos causados por&nbsp;<strong>Abstra\u00e7\u00e3o do \u00e1tomo 4\u2032-H<\/strong>&nbsp;na quebra da desoxirribose \u2192 na espinha dorsal do ADN<\/li>\n\n\n\n<li>Resultante&nbsp;<strong>propensoes de base livre<\/strong>&nbsp;(por exemplo, da timina) contribuem para a citotoxicidade<\/li>\n\n\n\n<li>Os danos no ADN conduzem a&nbsp;<strong>Paragem do ciclo celular na fase G\u2082<\/strong>&nbsp;\u2192 Inibi\u00e7\u00e3o da mitose \u2192&nbsp;<strong>Apoptose<\/strong><\/li>\n\n\n\n<li>A bleomicina actua como&nbsp;<strong>Pseudoenzima<\/strong>, que pode catalisar danos no ADN v\u00e1rias vezes.&nbsp;<\/li>\n\n\n\n<li>Inibi\u00e7\u00e3o adicional da&nbsp;<strong>ADN polimerase dependente de ADN<\/strong>.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"9-cisplatin-carboplatin\"><span class=\"ez-toc-section\" id=\"Cisplatin_Carboplatin\"><\/span><strong>Cisplatina \/ Carboplatina<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Ambos actuam como&nbsp;<strong>Alquilanos \u00e0 base de platina<\/strong>, forma ap\u00f3s ativa\u00e7\u00e3o intracelular&nbsp;<strong>aquocomplexos electrof\u00edlicos<\/strong>. Estes ligam-se preferencialmente a&nbsp;<strong>Posi\u00e7\u00e3o N7 da guanina e da adenina<\/strong>&nbsp;no ADN.<br>Emerg\u00eancia&nbsp;<strong>Liga\u00e7\u00f5es cruzadas de ADN<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Liga\u00e7\u00e3o cruzada intratransversal<\/strong>&nbsp;(dentro de um fio)<\/li>\n\n\n\n<li><strong>Liga\u00e7\u00e3o cruzada entre cadeias<\/strong>&nbsp;(entre os dois fios)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Bloqueio da deforma\u00e7\u00e3o do ADN&nbsp;<strong>Replica\u00e7\u00e3o e transcri\u00e7\u00e3o<\/strong>.&nbsp;<br>Ativa\u00e7\u00e3o de&nbsp;<strong>Respostas a danos no ADN<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>ativa\u00e7\u00e3o do p53<\/strong>&nbsp;\u2192 Paragem do ciclo celular (normalmente na fase G2\/M)<\/li>\n\n\n\n<li>Indu\u00e7\u00e3o de&nbsp;<strong>Apoptose<\/strong>&nbsp;atrav\u00e9s de vias mitocondriais e dependentes da caspase<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Efeitos adicionais:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Inibi\u00e7\u00e3o da&nbsp;<strong>Repara\u00e7\u00e3o do ADN<\/strong><\/li>\n\n\n\n<li>Inibi\u00e7\u00e3o da&nbsp;<strong>Atividade da telomerase<\/strong><\/li>\n\n\n\n<li>Indu\u00e7\u00e3o de&nbsp;<strong>Muta\u00e7\u00f5es pontuais<\/strong><\/li>\n\n\n\n<li>Em concentra\u00e7\u00f5es elevadas:&nbsp;<strong>Hiperactiva\u00e7\u00e3o da PARP<\/strong>&nbsp;\u2192 Degrada\u00e7\u00e3o de NAD+\/ATP \u2192 Necrose<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Carboplatina<\/strong>&nbsp;actua mais lentamente, mas tem o mesmo mecanismo de a\u00e7\u00e3o que a cisplatina \u2192&nbsp;<strong>Resist\u00eancia cruzada<\/strong>&nbsp;poss\u00edvel.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"9-cyclophosphamid\"><span class=\"ez-toc-section\" id=\"Cyclophosphamid\"><\/span><strong>Ciclofosfamida<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">A ciclofosfamida \u00e9 um&nbsp;<strong>Prodrug<\/strong>, que \u00e9 produzido no f\u00edgado por&nbsp;<strong>CYP2B6<\/strong>&nbsp;para&nbsp;<strong>4-hidroxiciclofosfamida<\/strong>&nbsp;\u00e9 convertido.&nbsp;<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Isto decomp\u00f5e-se em&nbsp;<strong>Aldofosfamida<\/strong>&nbsp;e para&nbsp;<strong>Fosforamida Mostarda<\/strong>&nbsp;(ativo) e&nbsp;<strong>Acrole\u00edna<\/strong><\/li>\n\n\n\n<li><strong>Fosforamida Mostarda<\/strong>&nbsp;actua como&nbsp;<strong>alquilano bifuncional<\/strong>Transfere grupos alquilo para o&nbsp;<strong>Posi\u00e7\u00e3o N7 da guanina<\/strong>&nbsp;no ADN<\/li>\n\n\n\n<li>Isto resulta em&nbsp;<strong>Liga\u00e7\u00f5es cruzadas ADN-ADN (liga\u00e7\u00f5es cruzadas)<\/strong>&nbsp;e&nbsp;<strong>Liga\u00e7\u00e3o cruzada ADN-prote\u00edna<\/strong>, que fixam as cadeias de ADN<\/li>\n\n\n\n<li>Bloquear as liga\u00e7\u00f5es cruzadas&nbsp;<strong>Replica\u00e7\u00e3o do ADN<\/strong>&nbsp;e&nbsp;<strong>Transcri\u00e7\u00e3o<\/strong>, conduzir a&nbsp;<strong>Quebras de fio<\/strong>&nbsp;e ativar&nbsp;<strong>p53<\/strong>-dependente&nbsp;<strong>Apoptose<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O efeito \u00e9&nbsp;<strong>Ciclo n\u00e3o espec\u00edfico<\/strong>, mas particularmente eficaz em c\u00e9lulas em prolifera\u00e7\u00e3o.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Acrole\u00edna<\/strong>&nbsp;provoca a&nbsp;<strong>Les\u00f5es da bexiga<\/strong>&nbsp;(cistite hemorr\u00e1gica).<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"9-cytarabin-ara-c\"><span class=\"ez-toc-section\" id=\"Cytarabin_Ara-C\"><\/span><strong>Citarabina (Ara-C)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>A citarabina \u00e9 convertida intracelularmente em&nbsp;<strong>Ara-CTP<\/strong>&nbsp;fosforilado, o metabolito ativo<\/li>\n\n\n\n<li>Ara-CTP&nbsp;<strong>inibe a ADN polimerase<\/strong>&nbsp;e \u00e9 incorretamente incorporado no ADN \u2192&nbsp;<strong>Termina\u00e7\u00e3o da cadeia de ADN<\/strong><\/li>\n\n\n\n<li>Bloqueio do&nbsp;<strong>Replica\u00e7\u00e3o e repara\u00e7\u00e3o do ADN<\/strong>&nbsp;\u2192 Paragem do ciclo celular no&nbsp;<strong>Fase S<\/strong><\/li>\n\n\n\n<li>Indu\u00e7\u00e3o de&nbsp;<strong>Apoptose<\/strong>&nbsp;atrav\u00e9s da resposta aos danos no ADN (por exemplo, ativa\u00e7\u00e3o do p53)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O efeito \u00e9&nbsp;<strong>Espec\u00edfico da fase do ciclo<\/strong>&nbsp;(apenas em c\u00e9lulas em prolifera\u00e7\u00e3o)<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Dacarbacin\"><\/span>Dacarbacina<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">A dacarbazina \u00e9 um&nbsp;<strong>Prodrug<\/strong>, que \u00e9 produzido no f\u00edgado por&nbsp;<strong>Citocromo P450<\/strong>&nbsp;para&nbsp;<strong>Monometiltriazenilimidazol carboxamida (MTIC)<\/strong>&nbsp;\u00e9 metabolizado.  O MTIC decomp\u00f5e-se espontaneamente numa subst\u00e2ncia reactiva&nbsp;<strong>Cati\u00e3o metilo<\/strong>, que \u00e9 conhecido como&nbsp;<strong>Alquilanos<\/strong>&nbsp;obras.&nbsp;<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Alquila\u00e7\u00e3o do ADN<\/strong>O cati\u00e3o metilo liga-se principalmente ao&nbsp;<strong>Posi\u00e7\u00e3o O-6 e N-7 da guanina<\/strong>&nbsp;no ADN<\/li>\n\n\n\n<li>Isto leva a&nbsp;<strong>Quebras da cadeia de ADN<\/strong>,&nbsp;<strong>Incompatibilidades<\/strong>&nbsp;durante a replica\u00e7\u00e3o e&nbsp;<strong>Bloqueio da s\u00edntese de ADN<\/strong><\/li>\n\n\n\n<li>Ativar os danos&nbsp;<strong>Sistemas de repara\u00e7\u00e3o do ADN<\/strong>, mas a sobrecarga ou a repara\u00e7\u00e3o ineficiente (por exemplo, baixa atividade da MGMT) resulta em&nbsp;<strong>Apoptose<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O efeito \u00e9&nbsp;<strong>Independente do ciclo<\/strong>, mas particularmente eficaz em c\u00e9lulas em prolifera\u00e7\u00e3o<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"9-dexamethason\"><span class=\"ez-toc-section\" id=\"Dexamethason\"><\/span><strong>Dexametasona<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Liga-se ao sistema intracelular&nbsp;<strong>Receptores de glucocortic\u00f3ides<\/strong>&nbsp;\u2192 O complexo migra para o n\u00facleo da c\u00e9lula.&nbsp;<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Transrepress\u00e3o<\/strong>Inibe os factores de transcri\u00e7\u00e3o&nbsp;<strong>NF-\u03baB<\/strong>&nbsp;e&nbsp;<strong>AP-1<\/strong>&nbsp;\u2192 reduz a express\u00e3o dos genes pr\u00f3-inflamat\u00f3rios (citocinas como a IL-1, IL-6, TNF-\u03b1; enzimas como a fosfolipase A2, COX-2)<\/li>\n\n\n\n<li><strong>Transactiva\u00e7\u00e3o<\/strong>Ativa genes anti-inflamat\u00f3rios (por exemplo, para I\u03baB, que inibe o NF-\u03baB)<\/li>\n\n\n\n<li><strong>Nas c\u00e9lulas linf\u00e1ticas<\/strong><br>ativa o&nbsp;<strong>via intr\u00ednseca da apoptose<\/strong>&nbsp;\u2192 Permeabiliza\u00e7\u00e3o mitocondrial, liberta\u00e7\u00e3o de citocromo c, ativa\u00e7\u00e3o da caspase-9<\/li>\n\n\n\n<li><strong>Nos fibroblastos<\/strong><br>espect\u00e1culos&nbsp;<strong>efeito anti-apopt\u00f3tico<\/strong>&nbsp;sobre:<br>- Indu\u00e7\u00e3o do&nbsp;<strong>Esfingosina quinase 1<\/strong>&nbsp;\u2192 Aumento da produ\u00e7\u00e3o de&nbsp;<strong>Esfingosina-1-fosfato (S1P)<\/strong><br>- Ativa\u00e7\u00e3o do&nbsp;<strong>Via de sinaliza\u00e7\u00e3o PI3K\/Akt<\/strong><br>- Regula\u00e7\u00e3o positiva da prote\u00edna anti-apopt\u00f3tica&nbsp;<strong>Bcl-xL<\/strong><br>- Preserva\u00e7\u00e3o do potencial de membrana mitocondrial<\/li>\n\n\n\n<li>Inibe&nbsp;<strong>Fosfolipase A2<\/strong>&nbsp;\u2192 Redu\u00e7\u00e3o da liberta\u00e7\u00e3o de mediadores pr\u00f3-inflamat\u00f3rios<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"9-doxorubicin\"><span class=\"ez-toc-section\" id=\"Doxorubicin\"><\/span><strong>Doxorrubicina<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Intercala\u00e7\u00e3o de ADN<\/strong>A mol\u00e9cula planar intercala-se entre os pares de bases do ADN de uma forma espec\u00edfica da sequ\u00eancia \u2192 interfere com as h\u00e9lices, bloqueia&nbsp;<strong>Replica\u00e7\u00e3o do ADN<\/strong>&nbsp;e&nbsp;<strong>Transcri\u00e7\u00e3o<\/strong><\/li>\n\n\n\n<li><strong>Inibi\u00e7\u00e3o da Topoisomerase II<\/strong>A doxorrubicina estabiliza a&nbsp;<strong>Complexo de clivagem do ADN da Topoisomerase II<\/strong>&nbsp;\u2192 Impede a reunifica\u00e7\u00e3o das cadeias de ADN \u2192 Conduz a&nbsp;<strong>Quebras de cadeia dupla<\/strong><\/li>\n\n\n\n<li><strong>Forma\u00e7\u00e3o de ERO<\/strong>A estrutura da quinona \u00e9 reduzida a um radical semiquinona \u2192 gerado&nbsp;<strong>esp\u00e9cies reactivas de oxig\u00e9nio (ROS)<\/strong>&nbsp;\u2192 Danos oxidativos no ADN, l\u00edpidos e prote\u00ednas \u2192 Quebras da cadeia de ADN<\/li>\n\n\n\n<li><strong>Din\u00e2mica da cromatina<\/strong>Aumenta o&nbsp;<strong>Tens\u00e3o de tor\u00e7\u00e3o<\/strong>&nbsp;no ADN e promove&nbsp;<strong>Comuta\u00e7\u00e3o de nucleossomas<\/strong>&nbsp;\u2192 Exp\u00f5e o ADN a mais danos<\/li>\n\n\n\n<li><strong>Paragem do ciclo celular e apoptose<\/strong>Ativar danos no ADN&nbsp;<strong>p53<\/strong>&nbsp;e&nbsp;<strong>Sistemas de repara\u00e7\u00e3o do ADN<\/strong>&nbsp;\u2192 em caso de sobrecarga: paragem do ciclo celular (G2\/M) e&nbsp;<strong>Apoptose<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O efeito \u00e9&nbsp;<strong>Ciclo n\u00e3o espec\u00edfico<\/strong>, mas particularmente eficaz em c\u00e9lulas em prolifera\u00e7\u00e3o.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"9-etoposid\"><span class=\"ez-toc-section\" id=\"Etoposid\"><\/span><strong>Etoposido<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Inibe&nbsp;<strong>Topoisomerase II<\/strong>, uma enzima que desenrola o ADN durante a replica\u00e7\u00e3o e a transcri\u00e7\u00e3o<\/li>\n\n\n\n<li>Liga-se ao&nbsp;<strong>Complexo de ADN Topoisomerase II<\/strong>&nbsp;e estabiliza-o \u2192 impede a&nbsp;<strong>Re-liga\u00e7\u00e3o (reconex\u00e3o)<\/strong>&nbsp;das cadeias de ADN ap\u00f3s a clivagem<\/li>\n\n\n\n<li>Conduz a&nbsp;<strong>quebras persistentes da cadeia dupla<\/strong>&nbsp;no ADN<\/li>\n\n\n\n<li>Ativar danos no ADN&nbsp;<strong>p53<\/strong>&nbsp;e outros mecanismos de repara\u00e7\u00e3o \u2192 em caso de sobrecarga:&nbsp;<strong>Paragem do ciclo celular na fase G2<\/strong><\/li>\n\n\n\n<li>Indu\u00e7\u00e3o do&nbsp;<strong>Apoptose<\/strong>&nbsp;atrav\u00e9s de vias de sinaliza\u00e7\u00e3o mitocondriais e dependentes da caspase<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O efeito \u00e9&nbsp;<strong>Espec\u00edfico da fase do ciclo<\/strong>, especialmente no&nbsp;<strong>fase S tardia e G2<\/strong>.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Glukokortikoide_Prednison_Prednisolon\"><\/span><strong>Glucocortic\u00f3ides (prednisona \/ prednisolona)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Efeito gen\u00f3mico<\/strong><br>A prednisona \u00e9 convertida no f\u00edgado em&nbsp;<strong>Prednisolona<\/strong>&nbsp;(ativo). Ambos se ligam ao citoplasma&nbsp;<strong>Receptores de glucocortic\u00f3ides (GKR)<\/strong>.  O complexo transloca-se para o n\u00facleo da c\u00e9lula e modula a express\u00e3o gen\u00e9tica atrav\u00e9s de:<br>- <strong>Transactiva\u00e7\u00e3o<\/strong>Vincula\u00e7\u00e3o a&nbsp;<strong>Elementos de resposta aos glucocortic\u00f3ides (GRE)<\/strong>&nbsp;\u2192 aumento da express\u00e3o de genes anti-inflamat\u00f3rios (ex.&nbsp;&nbsp;<em>Lipocortina<\/em>, que inibe a fosfolipase A2)<br>- <strong>Transrepress\u00e3o<\/strong>Inibi\u00e7\u00e3o de factores de transcri\u00e7\u00e3o&nbsp;<strong>NF-\u03baB<\/strong>&nbsp;e&nbsp;<strong>AP-1<\/strong>&nbsp;\u2192 Redu\u00e7\u00e3o da produ\u00e7\u00e3o de citocinas pr\u00f3-inflamat\u00f3rias (IL-1, IL-2, IL-6, TNF-\u03b1, IFN-\u03b3), de enzimas (COX-2, fosfolipase A2) e de leucotrienos<\/li>\n\n\n\n<li><strong>Efeito n\u00e3o gen\u00f3mico<\/strong><br>- Em doses elevadas (por exemplo, por via intravenosa) efeito r\u00e1pido atrav\u00e9s dos receptores de membrana \u2192 melhoria da microcircula\u00e7\u00e3o em caso de choque, aumento do efeito das catecolaminas<\/li>\n\n\n\n<li><strong>Outros efeitos<\/strong><br>- Inibi\u00e7\u00e3o da prolifera\u00e7\u00e3o de fibroblastos e da s\u00edntese de colag\u00e9nio (antiproliferativo)<br>- Imunossupress\u00e3o atrav\u00e9s da inibi\u00e7\u00e3o da prolifera\u00e7\u00e3o de linf\u00f3citos T<br>- Efeitos metab\u00f3licos: Gluconeog\u00e9nese, lip\u00f3lise, prote\u00f3lise \u2192 aumento do a\u00e7\u00facar no sangue<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Ifosfamid\"><\/span><strong>Ifosfamida<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Prodrug<\/strong>\u00c9 produzido no f\u00edgado por&nbsp;<strong>Enzimas CYP450<\/strong>&nbsp;(por exemplo, CYP3A4) para&nbsp;<strong>4-Hidroxi-Ifosfamida<\/strong>&nbsp;ativado.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Convers\u00e3o espont\u00e2nea para&nbsp;<strong>Isoaldofosfamida<\/strong>, que em&nbsp;<strong>Isofosfamida-Perda<\/strong>&nbsp;(alquilante) e&nbsp;<strong>Acrole\u00edna<\/strong>&nbsp;desintegra-se<\/li>\n\n\n\n<li><strong>Isofosfamida-Perda<\/strong>&nbsp;transfere grupos alquilo para o&nbsp;<strong>Posi\u00e7\u00e3o N7 da guanina<\/strong>&nbsp;no ADN \u2192 provoca&nbsp;<strong>Quebras da cadeia de ADN<\/strong>&nbsp;e&nbsp;<strong>Reticula\u00e7\u00e3o inter e intralonga<\/strong><\/li>\n\n\n\n<li>Estes danos no ADN bloqueiam&nbsp;<strong>Replica\u00e7\u00e3o<\/strong>&nbsp;e&nbsp;<strong>Transcri\u00e7\u00e3o<\/strong>&nbsp;\u2192 conduzem a&nbsp;<strong>Paragem do ciclo celular na fase G2<\/strong><\/li>\n\n\n\n<li>Se os mecanismos de repara\u00e7\u00e3o forem sobrecarregados (por exemplo, pela MGMT) \u2192&nbsp;<strong>Apoptose<\/strong><\/li>\n\n\n\n<li><strong>Acrole\u00edna<\/strong>&nbsp;provoca a&nbsp;<strong>efeitos urot\u00f3xicos<\/strong>&nbsp;(por exemplo, cistite hemorr\u00e1gica)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O efeito \u00e9&nbsp;<strong>Ciclo n\u00e3o espec\u00edfico<\/strong>, mas particularmente eficaz em c\u00e9lulas em prolifera\u00e7\u00e3o.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Possibilidade de resist\u00eancia cruzada com a ciclofosfamida<\/strong>, mas tamb\u00e9m <strong>Atividade em tumores resistentes \u00e0 ciclofosfamida<\/strong>.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Procarbazin\"><\/span>Procarbazina<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">\u00c9 oxidado no f\u00edgado (via CYP450) e espontaneamente em&nbsp;<strong>Azo-procarbazina<\/strong>, depois continuar para&nbsp;<strong>Metilazoxi<\/strong>&nbsp;e&nbsp;<strong>Compostos benzilazoxi<\/strong>.&nbsp;<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Alquila\u00e7\u00e3o do ADN<\/strong>metabolitos activos (por exemplo.&nbsp;<strong>I\u00e3o metil diaz\u00f3nio<\/strong>) alquilam o&nbsp;<strong>Posi\u00e7\u00e3o N7 da guanina<\/strong>&nbsp;\u2192 conduz a&nbsp;<strong>Quebras de cadeia \u00fanica de ADN<\/strong>,&nbsp;<strong>Reticula\u00e7\u00e3o<\/strong>&nbsp;e&nbsp;<strong>Incompatibilidades<\/strong><\/li>\n\n\n\n<li><strong>Inibi\u00e7\u00e3o da s\u00edntese proteica<\/strong> inibe a&nbsp;<strong>Transmetila\u00e7\u00e3o da metionina no ARNt<\/strong>&nbsp;\u2192 ARN-t defeituoso \u2192 Cessa\u00e7\u00e3o da s\u00edntese proteica \u2192 Inibi\u00e7\u00e3o secund\u00e1ria da s\u00edntese de ADN e ARN<\/li>\n\n\n\n<li><strong>Forma\u00e7\u00e3o de ERO<\/strong> - \u00e9 formado durante a auto-oxida\u00e7\u00e3o&nbsp;<strong>Per\u00f3xido de hidrog\u00e9nio<\/strong>&nbsp;\u2192 Danos oxidativos nas prote\u00ednas (por exemplo, grupos sulfidrilo)<\/li>\n\n\n\n<li><strong>Paragem do ciclo celular<\/strong> - Os danos activam os mecanismos de repara\u00e7\u00e3o do ADN \u2192&nbsp;<strong>Paragem do ciclo celular<\/strong>&nbsp;\u2192 em caso de sobrecarga&nbsp;<strong>Apoptose<\/strong><\/li>\n\n\n\n<li><strong>Efeito adicional<\/strong> \u00e9 um fraco&nbsp;<strong>Inibi\u00e7\u00e3o da MAO<\/strong>&nbsp;(sistema nervoso central)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Rituximab\"><\/span><strong>Rituximab<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O nome resulta de<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>RI<\/strong>&nbsp;- Vari\u00e1vel (definida pelo fabricante)<\/li>\n\n\n\n<li><strong>tu<\/strong>&nbsp;- para \u201etumor\u201c<\/li>\n\n\n\n<li><strong>xi<\/strong>&nbsp;- para \u201equim\u00e9rico\u201c (a regi\u00e3o vari\u00e1vel \u00e9 murina, a regi\u00e3o constante \u00e9 humana)<\/li>\n\n\n\n<li><strong>m\u00e3e<\/strong>&nbsp;- para \u201eanticorpo monoclonal\u201c&nbsp;<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">O rituximab liga-se ao&nbsp;<strong>Antig\u00e9nio CD20<\/strong>&nbsp;nas c\u00e9lulas B e ativa v\u00e1rios mecanismos de a\u00e7\u00e3o:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Citotoxicidade mediada por c\u00e9lulas dependente de anticorpos (ADCC)<\/strong>A regi\u00e3o Fc do anticorpo ativa as c\u00e9lulas assassinas naturais que destroem a c\u00e9lula alvo<\/li>\n\n\n\n<li><strong>Citotoxicidade dependente do complemento (CDC)<\/strong>Ativa\u00e7\u00e3o do sistema do complemento (via C1q) \u2192 Forma\u00e7\u00e3o do complexo de ataque \u00e0 membrana \u2192 Lise celular<\/li>\n\n\n\n<li><strong>Indu\u00e7\u00e3o direta de apoptose<\/strong>Via de sinaliza\u00e7\u00e3o mediada por CD20 \u2192 Ativa\u00e7\u00e3o de&nbsp;<strong>p38 MAP quinase<\/strong>&nbsp;\u2192 morte celular programada (apoptose), especialmente ap\u00f3s a liga\u00e7\u00e3o cruzada do anticorpo<\/li>\n\n\n\n<li><strong>Fagocitose<\/strong>Macr\u00f3fagos reconhecem e fagocitam c\u00e9lulas B marcadas<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Estes mecanismos conduzem a <strong>elimina\u00e7\u00e3o selectiva de c\u00e9lulas B CD20-positivas sem afetar as c\u00e9lulas estaminais da medula \u00f3ssea<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">O rituximab \u00e9 um c<em>Anticorpo monoclonal Himeric<\/em>, que prov\u00e9m de <em>murino<\/em> (rato) e os dom\u00ednios constantes humanos (humano), interage de forma \u00f3ptima com <em>Receptores Fc<\/em> (fragmento cristaliz\u00e1vel) em c\u00e9lulas efetoras<em>C\u00e9lulas NK, mon\u00f3citos, macr\u00f3fagos<\/em>) e o sistema de complemento.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Receptores Fc<\/strong>&nbsp;s\u00e3o&nbsp;<strong>Prote\u00ednas de membrana na superf\u00edcie de c\u00e9lulas imunit\u00e1rias<\/strong>, que reconhecem e se ligam \u00e0 parte Fc constante dos anticorpos.&nbsp;<br>Combinam a imunidade humoral (anticorpos) com a defesa celular, ativando c\u00e9lulas imunes assim que estas se ligam a c\u00e9lulas-alvo marcadas com anticorpos, como bact\u00e9rias, c\u00e9lulas tumorais ou v\u00edrus.<\/li>\n<\/ul>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>C\u00e9lulas NK<\/strong> s\u00e3o um <strong>Tipo de linf\u00f3cito do sistema imunit\u00e1rio inato<\/strong>, reconhecer e destruir c\u00e9lulas infectadas e tumorais sem ter de reconhecer antig\u00e9nios espec\u00edficos.<br>Assim que uma c\u00e9lula tem menos <em>Mol\u00e9culas MHC-I<\/em> (Prote\u00ednas de superf\u00edcie para a apresenta\u00e7\u00e3o de p\u00e9ptidos do interior da c\u00e9lula, por exemplo, em infe\u00e7\u00f5es virais ou forma\u00e7\u00e3o de tumores) geralmente apresentadas, s\u00e3o reconhecidas como estranhas e destru\u00eddas.<\/li>\n<\/ul>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Mon\u00f3citos<\/strong> surgem, tais como as c\u00e9lulas B (<em>Linf\u00f3citos B<\/em>), na medula \u00f3ssea e circulam no sangue como <strong>Parte da defesa imunit\u00e1ria n\u00e3o espec\u00edfica<\/strong>. Depois de migrarem para os tecidos, diferenciam-se em macr\u00f3fagos.<\/li>\n<\/ul>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Macr\u00f3fagos<\/strong> s\u00e3o derivados de mon\u00f3citos como <strong>fag\u00f3citos maduros<\/strong> O conjunto dos macr\u00f3fagos gere cerca de um milh\u00e3o de c\u00e9lulas por segundo! Eliminam as c\u00e9lulas mortas, destru\u00eddas e os detritos celulares. Um macr\u00f3fago pode fagocitar v\u00e1rias centenas a milhares de c\u00e9lulas por dia.<\/li>\n<\/ul>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Sistema complemento<\/strong> \u00e9 <strong>Componente essencial do sistema imunit\u00e1rio inato<\/strong>, composto por 30 prote\u00ednas que s\u00e3o produzidas no f\u00edgado e circulam no plasma para complementar o efeito dos anticorpos.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Isto significa:<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A estrutura do rituximab:<br><br>Dom\u00ednios vari\u00e1veis (parte Fab): MURINA (sequ\u00eancia do rato)<br>\u2502 \u2514\u2500 Esta parte reconhece CD20<br>Dom\u00ednios constantes (parte Fc): HUMAN (sequ\u00eancia humana)<br>\u2502 \u2514\u2500 Esta parte ativa a ADCC, CDC<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Descobrir como e porqu\u00ea surgiu a hist\u00f3ria da sua cria\u00e7\u00e3o \u00e9 um desenvolvimento muito interessante que <a href=\"#hier\" data-type=\"internal\" data-id=\"#Rituximab\">aqui<\/a> \u00e9 descrito mais detalhadamente abaixo ...!<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Vincristin_Vinblastin\"><\/span><strong>Vincristina \/ vinblastina<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Vincula\u00e7\u00e3o a&nbsp;<strong>\u03b2-Tubulina<\/strong>&nbsp;e inibir a&nbsp;<strong>Polimeriza\u00e7\u00e3o de microt\u00fabulos<\/strong>.&nbsp;<\/li>\n\n\n\n<li>Perturbar a estrutura do&nbsp;<strong>fuso mit\u00f3tico<\/strong>&nbsp;durante a metafase \u2192&nbsp;<strong>Mitosearrest<\/strong>.&nbsp;<\/li>\n\n\n\n<li>Conduzir a&nbsp;<strong>Paragem do ciclo celular na fase M<\/strong>&nbsp;e, por fim, para&nbsp;<strong>Apoptose<\/strong>.&nbsp;<\/li>\n\n\n\n<li>Efeito&nbsp;<strong>Espec\u00edfico da fase do ciclo<\/strong>&nbsp;contra c\u00e9lulas que se dividem rapidamente (por exemplo, c\u00e9lulas tumorais).<\/li>\n\n\n\n<li>A vinblastina pode tamb\u00e9m&nbsp;<strong>Cristalizar a tubulina<\/strong>&nbsp;sair.&nbsp;<\/li>\n\n\n\n<li>Ambas as subst\u00e2ncias prejudicam o transporte axonal \u2192 contribuem para a&nbsp;<strong>efeito secund\u00e1rio neurot\u00f3xico<\/strong>&nbsp;com.&nbsp;<\/li>\n\n\n\n<li>Inibi\u00e7\u00e3o adicional de&nbsp;<strong>S\u00edntese de ADN e ARN<\/strong>&nbsp;(efeito secund\u00e1rio).<\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"PTM\"><span class=\"ez-toc-section\" id=\"Phyto-Therapiemoglichkeiten\"><\/span>Op\u00e7\u00f5es de fitoterapia<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Todas as refer\u00eancias s\u00e3o da NIH National Library of Medicine do National Center of Biotechnology Information, <a href=\"https:\/\/www.google.com\/maps\/place\/8600+Rockville+Pike,+Bethesda,+MD+20894\/@38.9959508,-77.101021,17z\/data=!3m1!4b1!4m5!3m4!1s0x89b7c95e25765ddb:0x19156f88b27635b8!8m2!3d38.9959508!4d-77.0988323\" target=\"_blank\" rel=\"noreferrer noopener\">8600 Rockville Pike, Bethesda, MD 20894<\/a>, ou editoras reconhecidas. Procurou-se assegurar a inexist\u00eancia de conflitos de interesses, a fim de garantir um padr\u00e3o cient\u00edfico largamente objetivo.<br>Os artigos podem conter apenas resumos. No entanto, os textos completos est\u00e3o normalmente ligados no canto superior direito, quer se trate de publica\u00e7\u00f5es gratuitas ou pagas.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Os agentes radioprotectores mais conhecidos incluem<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Huaier-Pilz_Trametes_robiniophila_Murr\"><\/span><strong>Cogumelo de Huaier (Trametes robiniophila Murr.)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O cogumelo Huaier \u00e9 utilizado na medicina tradicional chinesa (MTC) h\u00e1 s\u00e9culos e est\u00e1 a ganhar cada vez mais aten\u00e7\u00e3o na terapia complementar do cancro. Estudos indicam que os extractos de huaier podem&nbsp;<strong>Apoiar a fun\u00e7\u00e3o imunit\u00e1ria<\/strong>,&nbsp;<strong>Reduzir os efeitos secund\u00e1rios da radioterapia<\/strong>&nbsp;e isso&nbsp;<strong>Reduzir o risco de recorr\u00eancia<\/strong>&nbsp;pode.<br>Particularmente relevante \u00e9 o seu efeito sobre a&nbsp;<strong>Fun\u00e7\u00e3o protetora da medula \u00f3ssea<\/strong>&nbsp;e o&nbsp;<strong>Estimula\u00e7\u00e3o das c\u00e9lulas imunit\u00e1rias<\/strong>, que \u00e9 de grande import\u00e2ncia na radioterapia, uma vez que a radia\u00e7\u00e3o pode danificar a medula \u00f3ssea e prejudicar a hematopoiese.<br>O cogumelo cont\u00e9m polissac\u00e1ridos e peptidoglicanos bioactivos, que t\u00eam um efeito imunomodulador e anti-tumoral.<br><br>\u00c9 de notar que a percentagem de <a href=\"https:\/\/nutrimentas-shop.de\/products\/vitalpilz-huaier-trametes-robiniophila-fur-wissenschaftliche-zwecke\" target=\"_blank\" rel=\"noreferrer noopener\">Polissac\u00e1ridos 32%<\/a> o teor das frac\u00e7\u00f5es de \u03b2-glucanos deve tamb\u00e9m ser determinado utilizando <a href=\"https:\/\/cdn.shopify.com\/s\/files\/1\/0699\/3782\/4012\/files\/Phytolab_Beta_Glucane.pdf?v=1771581121\" target=\"_blank\" rel=\"noreferrer noopener\">An\u00e1lises laboratoriais<\/a> \u00e9 comprovadamente de cerca de 47%, uma vez que ambos s\u00e3o os principais ingredientes activos para os quais os efeitos comprovados por estudos tamb\u00e9m est\u00e3o presentes!<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben\"><\/span><strong>Refer\u00eancias<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">- Hong Tang, Yujuan Yi, Yuru Yang, Qi Dai, Ziyan Zhao, Ning Jiang, Han Wang, Kangzi Li, Jianing Liu, Jia Li,&nbsp;<br>Zheng - Sun 3 de junho de 2024 - <a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S175646462400269X\" target=\"_blank\" rel=\"noopener\">Potenciais benef\u00edcios terap\u00eauticos do Huaier no cancro do aparelho digestivo: os seus componentes qu\u00edmicos, aplica\u00e7\u00f5es farmacol\u00f3gicas e orienta\u00e7\u00e3o futura<\/a><br>- Hongrong Long, Zhngcai Wu - Front Immunol. 2023 Jun 28 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/37449208\/\" target=\"_blank\" rel=\"noopener\">Efeitos imunoreguladores do Huaier (Trametes robiniophila Murr) e aplica\u00e7\u00f5es cl\u00ednicas relevantes<\/a><br>- Qu P, Han J, Qiu Y, Yu H, Hao J, Jin R, Zhou F. - Biomed Pharmacother. 2019 Set - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31202171\/\" target=\"_blank\" rel=\"noopener\">O extrato de Huaier aumenta a efic\u00e1cia do tratamento com imatinib na leucemia linfobl\u00e1stica aguda Ik6(+) Ph(+).<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Reishi_Ganoderma_lucidum\"><\/span><strong>Reishi (Ganoderma lucidum)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Conhecido como o \u201ecogumelo da imortalidade\u201c, o reishi tem os seguintes efeitos<strong>imunomodulador<\/strong>,&nbsp;<strong>anti-inflamat\u00f3rio<\/strong>&nbsp;e&nbsp;<strong>protege o f\u00edgado<\/strong>.<br>Pode aumentar a resist\u00eancia ao stress e apoiar a regenera\u00e7\u00e3o ap\u00f3s danos causados pela radia\u00e7\u00e3o.<br>Os triterpenos e os beta-glucanos favorecem a atividade dos macr\u00f3fagos e das c\u00e9lulas NK.<br><\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-2\"><\/span><strong>Refer\u00eancias<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">- Jiao C, Chen W, Tan X, Liang H, Li J, Yun H, He C, Chen J, Ma X, Xie Y, Yang BB - J Ethnopharmacol. 2020 Jan 30 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31586690\/\" target=\"_blank\" rel=\"noopener\">O \u00f3leo de esporos de Ganoderma lucidum induz a apoptose das c\u00e9lulas do cancro da mama in vitro e in vivo atrav\u00e9s da ativa\u00e7\u00e3o da caspase-3 e da caspase-9<\/a><br>- Lihua Chen, Abudumijiti Abulizi, Min Li - 28 de novembro de 2019 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31777016\/\" target=\"_blank\" rel=\"noreferrer noopener\">Efeito protetor do Ganoderma (Lingzhi) na radia\u00e7\u00e3o e na quimioterapia<\/a><br>- Xirui He, Xiaoxiao Wang, Jiacheng Fang, Yu Chang, Ning Ning, Hao Guo, Linhong Huang, Xiaoqiang Huang,<br>Zefeng Zhao - 06 de abril de 2017 - <a href=\"https:\/\/www.cochranelibrary.com\/cdsr\/doi\/10.1002\/14651858.CD007731.pub3\/full\" target=\"_blank\" rel=\"noreferrer noopener\"><em>Ganoderma lucidum<\/em>&nbsp;(cogumelo Reishi) para o tratamento do cancro<\/a><br>- Calvi\u00f1o E, Pajuelo L, Casas JA, Manj\u00f3n JL, Tejedor MC, Herr\u00e1ez A, Alonso MD, Diez JC. - Phytother Res. 2011 Jan - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/20568239\/\" target=\"_blank\" rel=\"noopener\">A\u00e7\u00e3o citot\u00f3xica do Ganoderma lucidum nas c\u00e9lulas do linfoma dependente de interleucina-3 DA-1: envolvimento de prote\u00ednas da apoptose<\/a><br>- M\u00fcller CI, Kumagai T, O'Kelly J, Seeram NP, Heber D, Koeffler HP. - Leuk Res. 2006 Jul - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/16423392\/\" target=\"_blank\" rel=\"noopener\">Ganoderma lucidum provoca apoptose em c\u00e9lulas de leucemia, linfoma e mieloma m\u00faltiplo.<\/a><br>- Dr. Silke Fischer - 11 de dezembro de 2025 - <a href=\"https:\/\/www.curivo.info\/der-heilpilz-ganoderma-lucidum-reishi-in-der-modernen-medizin-ein-evidenzbasierter-uebersichtsartikel-fuer-das-fachpublikum#\" target=\"_blank\" rel=\"noopener\">O cogumelo medicinal Ganoderma lucidum (Reishi) na medicina moderna: um artigo de revis\u00e3o baseado em provas para o p\u00fablico profissional<\/a><br><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Shiitake_Lentinula_edodes\"><\/span><strong>Shiitake (Lentinula edodes)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Cont\u00e9m lentinano e beta-glucanos, que&nbsp;<strong>Atividade das c\u00e9lulas imunit\u00e1rias<\/strong>&nbsp;como as c\u00e9lulas NK e os macr\u00f3fagos.<br>Os estudos mostram uma&nbsp;<strong>Efeito antimicrobiano e antiviral<\/strong>, que \u00e9 \u00fatil no caso de riscos infecciosos ap\u00f3s a radioterapia.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-3\"><\/span><strong>Refer\u00eancias<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">- Egilius L.H. Spierings, Hajime Fujii, Buxiang Sun, Thomas Walshe - 14 de mar\u00e7o de 2007 - <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18202543\" target=\"_blank\" rel=\"noreferrer noopener\">Um estudo de fase I sobre a seguran\u00e7a do suplemento nutricional, composto ativo correlacionado com hexose, AHCC, em volunt\u00e1rios saud\u00e1veis<\/a><br>- Joichi Matsui, Juna Uhara, Sohei Satoi, Masaki Kaibori, Hitoshi Yamada, Hiroaki Kitade, Atsusi Imamura, Soichiro Takai, Yusai Kawaguchi, A-Hon Kwon, Yasuo Kamiyama - 18 de mar\u00e7o de 2002 - <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/12076865\" target=\"_blank\" rel=\"noreferrer noopener\">Melhoria do progn\u00f3stico de pacientes com carcinoma hepatocelular p\u00f3s-operat\u00f3rio quando tratados com alimentos funcionais: um estudo de coorte prospetivo<\/a><br>- Kyoku Shimizu, Shinya Watanabe, Seiji Watanabe, Kenji Matsuda, Tetsuya Suga, Sabburo Nakazawa, Keiko Shiratori - Hepatogastroenterology 2009 Jan-Feb - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/19453066\/\" target=\"_blank\" rel=\"noreferrer noopener\">Efic\u00e1cia do lentinano disperso superfino administrado por via oral no cancro pancre\u00e1tico avan\u00e7ado<\/a> <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19453066\" target=\"_blank\" rel=\"noreferrer noopener\">Fonte 4<\/a><br>- <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/18670743\/\" target=\"_blank\" rel=\"noreferrer noopener\">Aplica\u00e7\u00e3o cl\u00ednica de uma terapia combinada de lentinan, RFA multi-electrodo e TACE no CHC<\/a> <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18670743\" target=\"_blank\" rel=\"noreferrer noopener\">Fonte 5<\/a><br><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Maitake_Grifola_frondosa\"><\/span><strong>Maitake (Grifola frondosa)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Rico em beta-glucanos, que&nbsp;<strong>Refor\u00e7ar a defesa imunit\u00e1ria<\/strong>&nbsp;e o&nbsp;<strong>Favorecer a regenera\u00e7\u00e3o celular<\/strong>.<br>Estudos indicam um papel na&nbsp;<strong>Regula\u00e7\u00e3o do a\u00e7\u00facar no sangue<\/strong>&nbsp;e&nbsp;<strong>Gest\u00e3o do peso<\/strong>&nbsp;aspectos importantes da nutri\u00e7\u00e3o durante e ap\u00f3s a radioterapia.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-4\"><\/span><strong>Refer\u00eancias<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">- Yanli He, Lijuan Zhang, Hua Wang - 2019 Mar 25 - <a href=\"https:\/\/www.sciencedirect.com\/science\/chapter\/bookseries\/abs\/pii\/S1877117319300316?via%3Dihub\" target=\"_blank\" rel=\"noreferrer noopener\">Actividades biol\u00f3gicas do polissac\u00e1rido antitumoral de Grifola frondosa<\/a><br>- Xirui He, Xiaoxiao Wang, Jiacheng Fang, Yu Chang, Ning Ning, Hao Guo, Linhong Huang, Xiaoqiang Huang,&nbsp;<br>Zefeng Zhao - 6 de abril de 2017 - International Journal of Biological Macromolecules - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/28366857\/\" target=\"_blank\" rel=\"noreferrer noopener\">Polissac\u00e1ridos no cogumelo Grifola frondosa e as suas propriedades promotoras de sa\u00fade: uma revis\u00e3o.<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Coriolus_Trametes_versicolor_Polyporus_umbellatus\"><\/span><strong>Coriolus (Trametes versicolor \/ Polyporus umbellatus)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Frequentemente utilizado como&nbsp;<strong>Terapia de acompanhamento para quimioterapia e radioterapia<\/strong>&nbsp;utilizado.<br>Ele&nbsp;<strong>melhora a qualidade de vida<\/strong>,&nbsp;<strong>refor\u00e7a o sistema imunit\u00e1rio<\/strong>&nbsp;e aumenta a&nbsp;<strong>Radiossensibilidade das c\u00e9lulas cancer\u00edgenas<\/strong> (a resposta \u00e0 radioterapia, - <strong>No entanto, a radiossensibilidade varia muito entre os diferentes tipos de tumores e mesmo dentro de um mesmo tumor<\/strong>.<br>O ingrediente&nbsp;<strong>PSK (polissac\u00e1rido crestina)<\/strong>&nbsp;tem sido bem estudado clinicamente.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-5\"><\/span><strong>Refer\u00eancias<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">- Habtemariam S. Biomedicines. - 2020 maio 25 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32466253\/\" target=\"_blank\" rel=\"noopener\">Polissac\u00e1ridos de Trametes versicolor (Synn. Coriolus versicolor) na terapia do cancro: alvos e efic\u00e1cia<\/a><br>- Yang CL, Chik SC, Lau AS, Chan GC, J Ethnopharmacol - 2023 Jan 30 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36208821\/\" target=\"_blank\" rel=\"noopener\">Coriolus versicolor e a sua mol\u00e9cula bioactiva s\u00e3o potenciais imunomoduladores contra a met\u00e1stase de c\u00e9lulas cancer\u00edgenas atrav\u00e9s da inativa\u00e7\u00e3o da via MAPK<\/a><br>- Pilkington K, Wieland LS, Teng L, Jin XY, Storey D, Liu JP. - Cochrane Database Syst Rev - 2022 Nov 29 -<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36445793\/\" target=\"_blank\" rel=\"noopener\">O cogumelo Coriolus (Trametes) versicolor para reduzir os efeitos adversos da quimioterapia ou da radioterapia em pessoas com cancro colorrectal<\/a><br>- Lau CB, Ho CY, Kim CF, Leung KN, Fung KP, Tse TF, Chan HH, Chow MS. - Life Sci. 2004 Jul 2 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/15183073\/\" target=\"_blank\" rel=\"noopener\">Actividades citot\u00f3xicas do extrato de Coriolus versicolor (Yunzhi) em c\u00e9lulas humanas de leucemia e linfoma por indu\u00e7\u00e3o de apoptose<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Berberin_Berberis_vulgaris\"><\/span><strong>Barb\u00e1ria<\/strong> (<strong>Berberis vulgaris<\/strong>)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Danos causados pela radioterapia<\/strong>Estudos pr\u00e9-cl\u00ednicos e cl\u00ednicos iniciais indicam que a berberina possui propriedades radioprotectoras, nomeadamente atrav\u00e9s de efeitos antioxidantes e anti-inflamat\u00f3rios. Um estudo piloto mostrou uma redu\u00e7\u00e3o dos efeitos secund\u00e1rios relacionados com a radia\u00e7\u00e3o em doentes com cancro.&nbsp;<\/li>\n<\/ul>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Linfomas<\/strong>Estudos in vitro e em animais mostram que a berberina pode inibir o crescimento de c\u00e9lulas de linfoma, por exemplo, suprimindo o mecanismo de escape imunit\u00e1rio CD47 no linfoma difuso de grandes c\u00e9lulas B. Foram igualmente observados efeitos sin\u00e9rgicos com agentes quimioterap\u00eauticos.<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-6\"><\/span><strong>Refer\u00eancias<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">- Mohammadian Haftcheshmeh S, Musavi M, Lotfi S, Soleimani A, Dodangeh M, Mohammadi A, Momtazi-Borojeni AA. - Inflammopharmacology. 2025 Ago - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40699408\/\" target=\"_blank\" rel=\"noopener\">A berberina como imunomodulador natural dos linf\u00f3citos B<\/a><br>- Cao YQ, Sun C, Li JY, Zhou X. - Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2024 Abr - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/38660879\/\" target=\"_blank\" rel=\"noopener\">Progresso da investiga\u00e7\u00e3o sobre o papel dos&nbsp;<strong>Berberina<\/strong>&nbsp;em doen\u00e7as malignas hematol\u00f3gicas e seus mecanismos relacionados -Revis\u00e3o<\/a><br>- Chang S, Li B, Xie Y, Wang Y, Xu Z, Jin S, Yu D, Wang H, Lu Y, Zhang Y, Ma R, Huang C, Lai W, Wu X, Zhu W, Shi J. - Neoplasia. 2022 Jan - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34890905\/\" target=\"_blank\" rel=\"noopener\">DCZ0014, um novo composto na terapia do linfoma difuso de grandes c\u00e9lulas B atrav\u00e9s da via de sinaliza\u00e7\u00e3o do recetor de c\u00e9lulas B<\/a><br>- Ren S, Cai Y, Hu S, Liu J, Zhao Y, Ding M, Chen X, Zhan L, Zhou X, Wang X. - Biochem Pharmacol. 2021 Jun - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33930347\/\" target=\"_blank\" rel=\"noopener\">A berberina exerce uma atividade antitumoral em grandes c\u00e9lulas B difusas&nbsp;<strong>linfoma<\/strong>&nbsp;atrav\u00e9s da modula\u00e7\u00e3o do eixo c-myc\/CD47<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Echinacea_Sonnenhut\"><\/span><strong>Equin\u00e1cea (flor de cone)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Refor\u00e7a a&nbsp;<strong>Imunidade inata<\/strong>&nbsp;estimulando os fag\u00f3citos e as c\u00e9lulas NK.<br>Frequentemente utilizado para constipa\u00e7\u00f5es e como parte de terapias para&nbsp;<strong>Defesa contra as infec\u00e7\u00f5es<\/strong>&nbsp;utilizado.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-7\"><\/span><strong>Refer\u00eancias<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">- Salama AAA, Elgohary R, Elwahab SA, Mostafa RE. - Sci Rep. 2025 Sep 2 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40897757\/\" target=\"_blank\" rel=\"noopener\">A Echinacea purpurea melhora a fibrose pulmonar induzida pela bleomicina em ratos atrav\u00e9s da modula\u00e7\u00e3o do eixo de sinaliza\u00e7\u00e3o da NADPH oxidase-4 e da endotelina-1\/fator de crescimento do tecido conjuntivo\/matriz de metaloproteinases.<\/a><br>- Mishima S, Saito K, Maruyama H, Inoue M, Yamashita T, Ishida T, Gu Y. - Biol Pharm Bull. 2004 Jul - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/15256730\/\" target=\"_blank\" rel=\"noopener\">Efeitos antioxidantes e imuno-refor\u00e7adores da Echinacea purpurea<\/a><br><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=%22Biol+Pharm+Bull%22%5Bjour%5D&amp;sort=date&amp;sort_order=desc\" target=\"_blank\" rel=\"noopener\"><\/a>- Hussien SM, Rashed ER - Resposta \u00e0 dose 2023 Jun 21 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/37359126\/\" target=\"_blank\" rel=\"noopener\">Impactos imuno-bioqu\u00edmicos da irradia\u00e7\u00e3o gama em ratos machos: um estudo de dose-resposta<\/a><br>- Joksi\u0107 G, Petrovi\u0107 S, Joksi\u0107 I, Leskovac A. - Arh Hig Rada Toksikol. 2009 Jun - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/19581209\/\" target=\"_blank\" rel=\"noopener\">Efeitos biol\u00f3gicos da Echinacea purpurea nas c\u00e9lulas sangu\u00edneas humanas<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Kurkuma_Curcumin\"><\/span><strong>A\u00e7afr\u00e3o-da-terra (curcumina)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Eficaz&nbsp;<strong>anti-inflamat\u00f3rio<\/strong>,&nbsp;<strong>antioxidante<\/strong>&nbsp;e&nbsp;<strong>protege as c\u00e9lulas do stress oxidativo<\/strong>, que \u00e9 causada pela radia\u00e7\u00e3o.<br>A curcumina pode melhorar a&nbsp;<strong>Apoiar a regenera\u00e7\u00e3o celular<\/strong>&nbsp;e o&nbsp;<strong>Refor\u00e7ar o efeito da radioterapia<\/strong>, sem danificar as c\u00e9lulas saud\u00e1veis.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-8\"><\/span><strong>Refer\u00eancias<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">- Zhang X, Cui Q, Yin L, Zhu J, Mao Y, Yin R, Shao H, Wang W, Sun X, Zhang Z, Gu C, Zhang M, Zhang R, Lu H, Cai Z, Li H, Yang Z. - Gut Microbes. 2025 Dez - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40671673\/\" target=\"_blank\" rel=\"noopener\">Nanopart\u00edculas semelhantes a ves\u00edculas derivadas do gengibre carregadas com curcumina para aliviar os danos intestinais induzidos pela radia\u00e7\u00e3o ionizante atrav\u00e9s da regula\u00e7\u00e3o do microbiota intestinal<\/a><br>- Xiu Z, Sun T, Yang Y, He Y, Yang S, Xue X, Yang W. - Oxid Med Cell Longev. 2022 Out 4 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36238646\/\" target=\"_blank\" rel=\"noopener\">A curcumina melhorou a morte celular imunog\u00e9nica induzida por radia\u00e7\u00e3o ionizante em c\u00e9lulas de glioma atrav\u00e9s das vias de sinaliza\u00e7\u00e3o do stress do ret\u00edculo endoplasm\u00e1tico<\/a><br>- Jagetia GC. - int J Radiat Biol. 2021 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33464136\/\" target=\"_blank\" rel=\"noopener\">A atividade antioxidante da curcumina protege contra a forma\u00e7\u00e3o de micron\u00facleos induzida pela radia\u00e7\u00e3o em culturas de linf\u00f3citos do sangue perif\u00e9rico humano expostos a v\u00e1rias doses de radia\u00e7\u00e3o gama<\/a><br><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Ingwer_Gingerole\"><\/span><strong>Gengibre (ginger\u00f3is)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Tem&nbsp;<strong>propriedades antimicrobianas e anti-inflamat\u00f3rias<\/strong>.<br>Apoia a digest\u00e3o e pode melhorar&nbsp;<strong>Atenuar os efeitos secund\u00e1rios das terap\u00eauticas<\/strong>.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-9\"><\/span><strong>Refer\u00eancias<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">- Zhang L, Hu R, Zhang J, Zhang H. - Colloids Surf B Biointerfaces. 2026 Fev - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41237471\/\" target=\"_blank\" rel=\"noopener\">Nanoplataforma de exossomas com duplo objetivo de co-entrega de doxorrubicina e bioactivos de Fuzi Lizhong Tang para uma terapia sin\u00e9rgica de DLBCL e gest\u00e3o da diarreia induzida por quimioterapia.<\/a><br>- Nafees S, Zafaryab M, Mehdi SH, Zia B, Rizvi MA, Khan MA. - Agentes Anticancer\u00edgenos Med Chem. 2021 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32951584\/\" target=\"_blank\" rel=\"noopener\">Efeito anti-cancer\u00edgeno do Gingerol na preven\u00e7\u00e3o e tratamento do cancro<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Zitrusfruchte_Quercetin\"><\/span><strong>Citrinos e quercetina<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">A quercetina das cebolas e dos citrinos apresenta&nbsp;<strong>Efeito antiviral e imunomodulador<\/strong>.<br>Os estudos est\u00e3o a investigar o seu papel na&nbsp;<strong>Refor\u00e7o da defesa imunit\u00e1ria<\/strong> (tamb\u00e9m no contexto de&nbsp;<strong>COVID-19<\/strong>).<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-10\"><\/span><strong>Refer\u00eancias<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">- Han P, Chu S, Shen J, Li L, Zhang Y, Wang S, Chen Y, Ma Y, Tang X, Gao C, Zheng X, Xu B, Wang Q, Yuan D, Li S. - Cell Metab. 2025 Dec 2 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41138722\/\" target=\"_blank\" rel=\"noopener\">O DOPAC, um metabolito microbiano derivado da quercetina, potencia a imunidade antitumoral das c\u00e9lulas T CD8(+) atrav\u00e9s da mitofagia mediada por NRF2<\/a><br>- Soofiyani SR, Hosseini K, Forouhandeh H, Ghasemnejad T, Tarhriz V, Asgharian P, Reiner \u017d, Sharifi-Rad J, Cho WC. - \u00d3xido Med C\u00e9lula Longev. 2021 agosto 2 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34381559\/\" target=\"_blank\" rel=\"noopener\">A quercetina como uma nova abordagem terap\u00eautica para o linfoma<\/a><br>- Granato M, Rizzello C, Gilardini Montani MS, Cuomo L, Vitillo M, Santarelli R, Gonnella R, D'Orazi G, Faggioni A, Cirone M. - J Nutr Biochem. 2017 Mar - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/28092744\/\" target=\"_blank\" rel=\"noopener\">A quercetina induz a apoptose e a autofagia em c\u00e9lulas de linfoma de efus\u00e3o prim\u00e1ria atrav\u00e9s da inibi\u00e7\u00e3o das vias de sinaliza\u00e7\u00e3o PI3K\/AKT\/mTOR e STAT3<\/a><br>- Li X, Wang X, Zhang M, Li A, Sun Z, Yu Q. - Cell Biochem Biophys. 2014 Nov - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/24902540\/\" target=\"_blank\" rel=\"noopener\">A quercetina potencia a atividade antitumoral do rituximab no linfoma difuso de grandes c\u00e9lulas B atrav\u00e9s da inibi\u00e7\u00e3o da via STAT3<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Schwarzkummelol_Nigella_sativa\"><\/span><strong>\u00d3leo de sementes de cominho preto (Nigella sativa)<\/strong><br><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Tem sido usado como um refor\u00e7o imunit\u00e1rio desde tempos imemoriais.<br>O contido&nbsp;<strong>Timoquinonas<\/strong>&nbsp;trabalho&nbsp;<strong>Antioxidante, anti-inflamat\u00f3rio e imunomodulador<\/strong>.<br>Apresenta efeitos positivos sobre o a\u00e7\u00facar no sangue, os n\u00edveis de l\u00edpidos no sangue e o sistema imunit\u00e1rio.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-11\"><\/span><strong>Refer\u00eancias<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">- Arslan BA, Isik FB, Gur H, Ozen F, Catal T. - Pharmacogn Mag. 2017 Oct - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/29142424\/\" target=\"_blank\" rel=\"noopener\">Efeito apopt\u00f3tico da Nigella sativa em c\u00e9lulas de linfoma humano U937<\/a><br>- Salomi NJ, Nair SC, Jayawardhanan KK, Varghese CD, Panikkar KR. - Cancer Lett. 1992 Mar 31 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/1555206\/\" target=\"_blank\" rel=\"noopener\">Princ\u00edpios antitumorais das sementes de Nigella sativa<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Ginseng_Panax_ginseng\"><\/span><strong>Ginseng (Panax ginseng)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Actua como&nbsp;<strong>Adaptog\u00e9nio<\/strong>, melhora a&nbsp;<strong>Resist\u00eancia ao stress<\/strong>&nbsp;e apoia o&nbsp;<strong>Produ\u00e7\u00e3o de energia<\/strong>&nbsp;ap\u00f3s as terapias.<br>Pode o&nbsp;<strong>Estabilizar a fun\u00e7\u00e3o imunit\u00e1ria<\/strong>&nbsp;e o&nbsp;<strong>Promover a regenera\u00e7\u00e3o<\/strong>.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-12\"><\/span><strong>Refer\u00eancias<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">- Li Q, Chen Y, Zhao X, Lu B, Qu T, Tang L, Zheng Q. - PLoS One. 2023 maio 19 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/37205671\/\" target=\"_blank\" rel=\"noopener\">Ginsen\u00f3sido 24-OH-PD do vermelho&nbsp;<strong>ginseng<\/strong>&nbsp;inibe a leucemia linfoc\u00edtica T aguda activando a via mitocondrial<\/a><br>- Pradhan P, Wen W, Cai H, Gao YT, Shu XO, Zheng W. - J Nutr. 2023 Apr - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36863482\/\" target=\"_blank\" rel=\"noopener\">Estudo de coorte prospetivo sobre o consumo de ginseng em associa\u00e7\u00e3o com o risco de cancro: Estudo sobre a sa\u00fade das mulheres de Xangai<\/a><br>- Lee SY, Shin YW, Hahm KB. - J Dig Dis. 2008 Ago - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/18956590\/\" target=\"_blank\" rel=\"noopener\">Fitoc\u00eauticos: armas poderosas mas ignoradas contra a infe\u00e7\u00e3o por Helicobacter pylori<\/a><\/p>\n\n\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Phyto-Therapeutika_%E2%80%93_Signalwege\"><\/span>Fito-terap\u00eautica - vias de sinaliza\u00e7\u00e3o<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Huaier_Trametes_robiniophila_Murr\"><\/span><strong>Huaier (Trametes robiniophila Murr.)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Os princ\u00edpios activos do cogumelo Huaier - nomeadamente os polissac\u00e1ridos, os proteoglicanos e os flavon\u00f3ides - interv\u00eam em v\u00e1rias vias de sinaliza\u00e7\u00e3o centrais:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>PI3K\/Akt\/mTOR<\/strong><br>A inibi\u00e7\u00e3o desta via de crescimento e de sobreviv\u00eancia \u2192 reduz a prolifera\u00e7\u00e3o e a indu\u00e7\u00e3o da apoptose nas c\u00e9lulas cancerosas<\/li>\n\n\n\n<li><strong>MAPK\/ERK e p38<\/strong><br>A modula\u00e7\u00e3o destas vias \u2192 influencia a prolifera\u00e7\u00e3o celular, a diferencia\u00e7\u00e3o e a resposta ao stress<\/li>\n\n\n\n<li><strong>TLR4\/NF-\u03baB<\/strong><br>Ativa\u00e7\u00e3o atrav\u00e9s de polissac\u00e1ridos \u2192 estimula as c\u00e9lulas imunit\u00e1rias (por exemplo, c\u00e9lulas dendr\u00edticas, macr\u00f3fagos) \u2192 melhora a resposta imunit\u00e1ria<\/li>\n\n\n\n<li><strong>AMPK<\/strong><br>Ativa\u00e7\u00e3o \u2192 promove o equil\u00edbrio energ\u00e9tico celular e inibe os processos anab\u00f3licos<\/li>\n\n\n\n<li><strong>YAP1 e Wnt\/\u03b2-catenina<\/strong><br>Inibi\u00e7\u00e3o das vias de sinaliza\u00e7\u00e3o oncog\u00e9nica \u2192 reduz o crescimento do tumor e as propriedades das c\u00e9lulas estaminais tumorais<\/li>\n\n\n\n<li><strong>TGF-\u03b2\/Smad<\/strong><br>Modula\u00e7\u00e3o \u2192 inibe os processos fibr\u00f3ticos nos \u00f3rg\u00e3os<\/li>\n\n\n\n<li><strong>Apoptose<\/strong>-<br>Indu\u00e7\u00e3o atrav\u00e9s de&nbsp;<strong>Caspase-3\/9<\/strong>,&nbsp;<strong>Aumento dos ERO<\/strong>&nbsp;e&nbsp;<strong>inibi\u00e7\u00e3o de mTOR<\/strong><\/li>\n\n\n\n<li><strong>Autofagia<\/strong><br>Promo\u00e7\u00e3o atrav\u00e9s da inibi\u00e7\u00e3o da mTOR e dos ERO \u2192 contribui para a desintoxica\u00e7\u00e3o (por exemplo, de prote\u00ednas de pico)<\/li>\n\n\n\n<li><strong>EMT (Transi\u00e7\u00e3o Epitelial-Mesenquimal)<\/strong><br>Escapamento via&nbsp;<strong>Regula\u00e7\u00e3o negativa de Snail e MMP-9<\/strong>&nbsp;\u2192 Reduz as met\u00e1stases<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Reishi_Ganoderma_lucidum-2\"><\/span><strong>Reishi (Ganoderma lucidum)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Imunomodula\u00e7\u00e3o<\/strong><br>Os polissac\u00e1ridos (por exemplo, \u03b2-glucanos) ligam-se a&nbsp;<strong>Dectina-1<\/strong>,&nbsp;<strong>TLRs<\/strong>&nbsp;e&nbsp;<strong>Recetor do complemento 3<\/strong>&nbsp;\u2192 ativar&nbsp;<strong>NF-\u03baB<\/strong>&nbsp;e&nbsp;<strong>MAPK<\/strong>&nbsp;\u2192 promovem a diferencia\u00e7\u00e3o e a ativa\u00e7\u00e3o de macr\u00f3fagos, c\u00e9lulas dendr\u00edticas e c\u00e9lulas NK<\/li>\n\n\n\n<li><strong>Inibi\u00e7\u00e3o da inflama\u00e7\u00e3o<\/strong><br>Os triterpenos inibem&nbsp;<strong>NF-\u03baB<\/strong>&nbsp;e isso&nbsp;<strong>NLRP3-Inflamassoma<\/strong>&nbsp;\u2192 reduzir a produ\u00e7\u00e3o de citocinas pr\u00f3-inflamat\u00f3rias (TNF-\u03b1, IL-1\u03b2, IL-6)<\/li>\n\n\n\n<li><strong>Neuroprotec\u00e7\u00e3o<\/strong><br>Inibi\u00e7\u00e3o da neuroinflama\u00e7\u00e3o, modula\u00e7\u00e3o da microglia, regula\u00e7\u00e3o positiva de&nbsp;<strong>BDNF<\/strong>&nbsp;\u2192 promove a neuroplasticidade; ativa\u00e7\u00e3o da&nbsp;<strong>Via de sinaliza\u00e7\u00e3o FGFR1<\/strong>&nbsp;\u2192 Aumenta a neurog\u00e9nese no hipocampo<\/li>\n\n\n\n<li><strong>Eixo intestino-c\u00e9rebro<\/strong><br>O Reishi modula o microbioma \u2192 aumenta&nbsp;<strong>Bifidobact\u00e9rias<\/strong>&nbsp;\u2192 melhora o metabolismo do triptofano \u2192 aumenta&nbsp;<strong>Serotonina (5-HT)<\/strong>&nbsp;no hipot\u00e1lamo \u2192 promotor do sono e regulador do humor<\/li>\n\n\n\n<li><strong>Ativa\u00e7\u00e3o da AMPK<\/strong><br>Regula o metabolismo energ\u00e9tico, promove a absor\u00e7\u00e3o de glucose, melhora a sensibilidade \u00e0 insulina (an\u00e1logo da metformina)<\/li>\n\n\n\n<li><strong>Anti-hipertensivo<\/strong><br>Inibir os p\u00e9ptidos&nbsp;<strong>ACE<\/strong>&nbsp;e ativar o&nbsp;<strong>Via de sinaliza\u00e7\u00e3o eNOS\/NO\/cGMP<\/strong>&nbsp;\u2192 leva \u00e0 vasodilata\u00e7\u00e3o<\/li>\n\n\n\n<li><strong>Antidiab\u00e9tico<\/strong><br>Ativado&nbsp;<strong>AMPK<\/strong>, melhora a fosforila\u00e7\u00e3o de&nbsp;<strong>RI<\/strong>,&nbsp;<strong>IRS1<\/strong>&nbsp;e&nbsp;<strong>Ato<\/strong>&nbsp;\u2192 Aumenta a sensibilidade \u00e0 insulina; inibe&nbsp;<strong>SREBP1c<\/strong>,&nbsp;<strong>FAS<\/strong>,&nbsp;<strong>SCD1<\/strong>&nbsp;\u2192 Suprime a lipog\u00e9nese<\/li>\n\n\n\n<li><strong>Antioxidante<\/strong><br>Reduz os ERO atrav\u00e9s da ativa\u00e7\u00e3o dos sistemas antioxidantes end\u00f3genos<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Shiitake_Lentinula_edodes-2\"><\/span><strong>Shiitake (Lentinula edodes)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Imunomodula\u00e7\u00e3o<\/strong><br>O polissac\u00e1rido&nbsp;<strong>Lentinan<\/strong>&nbsp;liga-se a&nbsp;<strong>Dectina-1<\/strong>,&nbsp;<strong>TLRs<\/strong>&nbsp;e&nbsp;<strong>Recetor do complemento 3<\/strong>&nbsp;\u2192 ativado&nbsp;<strong>NF-\u03baB<\/strong>&nbsp;e&nbsp;<strong>MAPK<\/strong>&nbsp;\u2192 Estimula macr\u00f3fagos, c\u00e9lulas dendr\u00edticas e c\u00e9lulas NK<\/li>\n\n\n\n<li><strong>Produ\u00e7\u00e3o de citocinas<\/strong><br>Lentinano induzido&nbsp;<strong>Interleucina-1 (IL-1)<\/strong>,&nbsp;<strong>Interleucina-2 (IL-2)<\/strong>,&nbsp;<strong>Interfer\u00e3o-\u03b3<\/strong>&nbsp;e&nbsp;<strong>TNF-\u03b1<\/strong>&nbsp;\u2192 Aumenta a resposta imunit\u00e1ria celular e a apoptose das c\u00e9lulas tumorais<\/li>\n\n\n\n<li><strong>Efeito antitumoral<\/strong><br>A Lentinan tem&nbsp;<strong>Sem citotoxicidade direta<\/strong>, mas refor\u00e7a indiretamente a luta contra os tumores atrav\u00e9s da ativa\u00e7\u00e3o imunit\u00e1ria \u2192 aumenta&nbsp;<strong>Produ\u00e7\u00e3o de anticorpos<\/strong>&nbsp;e&nbsp;<strong>interfer\u00e3o end\u00f3geno<\/strong><\/li>\n\n\n\n<li><strong>Indu\u00e7\u00e3o de apoptose<\/strong><br>Favorece a apoptose das c\u00e9lulas cancerosas atrav\u00e9s de&nbsp;<strong>Caspase-3\/8\/9<\/strong>-Ativa\u00e7\u00e3o e vias de sinaliza\u00e7\u00e3o mitocondrial<\/li>\n\n\n\n<li><strong>Antivirais<\/strong><br>Aumenta a resist\u00eancia aos v\u00edrus (por exemplo, da gripe) atrav\u00e9s da indu\u00e7\u00e3o de interfer\u00e3o<\/li>\n\n\n\n<li><strong>Metabolismo lip\u00eddico<\/strong><br>O ingrediente&nbsp;<strong>Eritadenina<\/strong>&nbsp;ativado&nbsp;<strong>Receptores de lipoprote\u00ednas no f\u00edgado<\/strong>&nbsp;\u2192 aumenta a absor\u00e7\u00e3o de LDL \u2192 reduz o colesterol LDL e VLDL<\/li>\n\n\n\n<li><strong>Anti-inflamat\u00f3rio<\/strong><br>Inibe&nbsp;<strong>NF-\u03baB<\/strong>&nbsp;e&nbsp;<strong>NLRP3-Inflamassoma<\/strong>&nbsp;\u2192 Reduz a inflama\u00e7\u00e3o<\/li>\n\n\n\n<li><strong>Regula\u00e7\u00e3o do microbioma<\/strong><br>Promove o crescimento de&nbsp;<strong>Bifidobact\u00e9rias<\/strong>&nbsp;e&nbsp;<strong>Lactobact\u00e9rias<\/strong>&nbsp;\u2192 Melhora a barreira intestinal e a regula\u00e7\u00e3o imunol\u00f3gica<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Maitake_Grifola_frondosa-2\"><\/span><strong>Maitake (Grifola frondosa)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Imunomodula\u00e7\u00e3o<\/strong><br>Os polissac\u00e1ridos (por exemplo, fra\u00e7\u00e3o D, Grifolan) ligam-se a&nbsp;<strong>TLR4<\/strong>,&nbsp;<strong>Dectina-1<\/strong>&nbsp;e&nbsp;<strong>Recetor do complemento 3<\/strong>&nbsp;\u2192 ativar&nbsp;<strong>TLR4-MyD88-IKK\u03b2-NF-\u03baB p65-Signalweg<\/strong>&nbsp;\u2192 Estimular macr\u00f3fagos, c\u00e9lulas dendr\u00edticas, c\u00e9lulas NK e c\u00e9lulas T citot\u00f3xicas<\/li>\n\n\n\n<li><strong>Equil\u00edbrio TH1\/TH2<\/strong><br>Mudan\u00e7a da resposta TH2 para TH1 \u2192 aumento da produ\u00e7\u00e3o de&nbsp;<strong>Interfer\u00e3o-\u03b3<\/strong>,&nbsp;<strong>IL-12<\/strong>,&nbsp;<strong>IL-18<\/strong>&nbsp;\u2192 Refor\u00e7a a defesa imunit\u00e1ria celular<\/li>\n\n\n\n<li><strong>Efeito antitumoral<\/strong><br>Indu\u00e7\u00e3o de&nbsp;<strong>Apoptose<\/strong>&nbsp;sobre o&nbsp;<strong>via de sinaliza\u00e7\u00e3o mitocondrial<\/strong>&nbsp;(Ativa\u00e7\u00e3o da caspase-3\/9) \u2192 Morte das c\u00e9lulas tumorais<\/li>\n\n\n\n<li><strong>Via de sinaliza\u00e7\u00e3o MAPK<\/strong><br>Ativar os polissac\u00e1ridos do maitake&nbsp;<strong>p38 MAPK<\/strong>&nbsp;e&nbsp;<strong>JNK<\/strong>&nbsp;\u2192 Promover a resposta imunit\u00e1ria e proteger contra a imunossupress\u00e3o<\/li>\n\n\n\n<li><strong>Regula\u00e7\u00e3o do a\u00e7\u00facar no sangue<\/strong><br>Inibi\u00e7\u00e3o da&nbsp;<strong>Alfa-glucosidase<\/strong>&nbsp;\u2192 Diminui a liberta\u00e7\u00e3o de glicose; aumenta a&nbsp;<strong>Sensibilidade \u00e0 insulina<\/strong>&nbsp;atrav\u00e9s dos polissac\u00e1ridos F2\/F3 e da glicoprote\u00edna SX.&nbsp;<\/li>\n\n\n\n<li><strong>Metabolismo<\/strong><br>Ativa\u00e7\u00e3o de&nbsp;<strong>PPAR\u03b4<\/strong>&nbsp;e vias de sinaliza\u00e7\u00e3o independentes da insulina \u2192 melhoram a toler\u00e2ncia \u00e0 glicose, reduzem os triglic\u00e9ridos e o colesterol<\/li>\n\n\n\n<li><strong>Regula\u00e7\u00e3o da tens\u00e3o arterial<\/strong><br>Influ\u00eancia na&nbsp;<strong>Sistema renina-angiotensina<\/strong>&nbsp;\u2192 Diminui\u00e7\u00e3o da press\u00e3o arterial sist\u00f3lica<\/li>\n\n\n\n<li><strong>Sa\u00fade intestinal<\/strong><br>Modula\u00e7\u00e3o do&nbsp;<strong>Microbiota intestinal<\/strong>&nbsp;\u2192 Aumento de&nbsp;<strong>Bifidobact\u00e9rias<\/strong>&nbsp;e&nbsp;<strong>\u00e1cidos gordos de cadeia curta<\/strong>&nbsp;\u2192 Anti-inflamat\u00f3rio e estabilizador do metabolismo<\/li>\n\n\n\n<li><strong>Antioxidante<\/strong><br>Ativa\u00e7\u00e3o de enzimas end\u00f3genas (SOD, glutati\u00e3o peroxidase) \u2192 reduz o stress oxidativo<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Coriolus_Trametes_versicolor_Polyporus_umbellatus-2\"><\/span><strong>Coriolus (Trametes versicolor \/ Polyporus umbellatus)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Imunomodula\u00e7\u00e3o<\/strong><br>Os p\u00e9ptidos polissac\u00e1ridos (PSP, PSK) ligam-se a&nbsp;<strong>TLRs<\/strong>&nbsp;(por exemplo, TLR2, TLR4),&nbsp;<strong>Dectina-1<\/strong>&nbsp;e&nbsp;<strong>Recetor do complemento 3<\/strong>&nbsp;\u2192 ativar&nbsp;<strong>NF-\u03baB<\/strong>&nbsp;e&nbsp;<strong>p38 MAPK<\/strong>&nbsp;\u2192 Estimular macr\u00f3fagos, c\u00e9lulas dendr\u00edticas, c\u00e9lulas NK e c\u00e9lulas T&nbsp;<\/li>\n\n\n\n<li><strong>Produ\u00e7\u00e3o de citocinas<\/strong><br>Indu\u00e7\u00e3o de&nbsp;<strong>IL-2<\/strong>,&nbsp;<strong>IFN-\u03b3<\/strong>,&nbsp;<strong>TNF-\u03b1<\/strong>&nbsp;e&nbsp;<strong>IL-6<\/strong>&nbsp;\u2192 refor\u00e7a a resposta imunit\u00e1ria celular<\/li>\n\n\n\n<li><strong>Efeito antitumoral<\/strong><br>Indiretamente atrav\u00e9s da ativa\u00e7\u00e3o imunit\u00e1ria; diretamente atrav\u00e9s de&nbsp;<strong>Paragem do ciclo celular<\/strong>&nbsp;e&nbsp;<strong>Indu\u00e7\u00e3o de apoptose<\/strong>&nbsp;nas c\u00e9lulas tumorais (por exemplo, atrav\u00e9s da ativa\u00e7\u00e3o da caspase)<\/li>\n\n\n\n<li><strong>Anti-inflamat\u00f3rio<\/strong><br>Modula\u00e7\u00e3o do&nbsp;<strong>Via de sinaliza\u00e7\u00e3o TLR4-MyD88-NF-\u03baB<\/strong>&nbsp;\u2192 Regula a resposta inflamat\u00f3ria<\/li>\n\n\n\n<li><strong>Inibi\u00e7\u00e3o de met\u00e1stases<\/strong><br>O PSK inibe&nbsp;<strong>Metaloproteinases (MMPs)<\/strong>&nbsp;\u2192 Reduz a invas\u00e3o tumoral<\/li>\n\n\n\n<li><strong>Prote\u00e7\u00e3o do f\u00edgado<\/strong><br>A PSP aumentou&nbsp;<strong>R\u00e1cio GSH\/GSSG<\/strong>&nbsp;\u2192 Prote\u00e7\u00e3o antioxidante contra danos hepatot\u00f3xicos<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Berberin_Berberis_vulgaris-2\"><\/span><strong>Barb\u00e1ria<\/strong> (<strong>Berberis vulgaris<\/strong>)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Indu\u00e7\u00e3o de apoptose<\/strong><br>Ativado&nbsp;<strong>p53<\/strong>,&nbsp;<strong>Caspase-3\/9<\/strong>,&nbsp;<strong>Citocromo c<\/strong>; inibe as prote\u00ednas anti-apopt\u00f3ticas, tais como&nbsp;<strong>Bcl-2<\/strong>&nbsp;e&nbsp;<strong>Mcl-1<\/strong><\/li>\n\n\n\n<li><strong>Paragem do ciclo celular<\/strong><br>Bloqueia as fases G1 e G2\/M atrav\u00e9s da regula\u00e7\u00e3o positiva de&nbsp;<strong>p21<\/strong>&nbsp;e&nbsp;<strong>GADD153<\/strong><\/li>\n\n\n\n<li><strong>Inibi\u00e7\u00e3o das vias de crescimento<\/strong><br>Inibido&nbsp;<strong>PI3K\/Akt\/mTOR<\/strong>,&nbsp;<strong>MAPK<\/strong>,&nbsp;<strong>NF-\u03baB<\/strong>,&nbsp;<strong>STAT3<\/strong>&nbsp;e&nbsp;<strong>Wnt\/\u03b2-catenina<\/strong><\/li>\n\n\n\n<li><strong>Efeito mitocondrial<\/strong><br>Perturba\u00e7\u00e3o do potencial de membrana \u2192&nbsp;<strong>Aumento dos ERO<\/strong>&nbsp;\u2192 Crise energ\u00e9tica nas c\u00e9lulas tumorais<\/li>\n\n\n\n<li><strong>Intera\u00e7\u00e3o do ADN<\/strong><br>Liga-se diretamente ao ADN e inibe&nbsp;<strong>Topoisomerase I<\/strong><\/li>\n\n\n\n<li><strong>Inibi\u00e7\u00e3o da inflama\u00e7\u00e3o<\/strong><br>Inibe&nbsp;<strong>NF-\u03baB<\/strong>&nbsp;e citocinas pr\u00f3-inflamat\u00f3rias (TNF-\u03b1, IL-6)<\/li>\n\n\n\n<li><strong>Antioxidante<\/strong><br>Ativado&nbsp;<strong>Nrf2\/HO-1<\/strong>- e&nbsp;<strong>AMPK<\/strong>-vias de sinaliza\u00e7\u00e3o \u2192 protege as c\u00e9lulas saud\u00e1veis<\/li>\n\n\n\n<li><strong>Imunomodula\u00e7\u00e3o<\/strong><br>Suprimido&nbsp;<strong>CD47<\/strong>&nbsp;(sinal \u201en\u00e3o me comas\u201c) \u2192 promove a fagocitose das c\u00e9lulas tumorais<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Echinacea_Sonnenhut-2\"><\/span><strong>Equin\u00e1cea (flor de cone)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Ativa\u00e7\u00e3o do recetor CB2<\/strong><br>As alquilamidas ligam-se ao recetor canabin\u00f3ide 2 (CB2) nas c\u00e9lulas imunit\u00e1rias \u2192 modulam a resposta imunit\u00e1ria sem efeitos psicoactivos<\/li>\n\n\n\n<li><strong>Via de sinaliza\u00e7\u00e3o cAMP-PKA<\/strong><br>A ativa\u00e7\u00e3o do CB2 aumenta o AMPc \u2192 ativa a PKA \u2192 regula o NF-\u03baB e a produ\u00e7\u00e3o de citocinas<\/li>\n\n\n\n<li><strong>Vias de sinaliza\u00e7\u00e3o MAPK<\/strong><br>Ativa\u00e7\u00e3o de&nbsp;<strong>p38\/MAPK<\/strong>,&nbsp;<strong>JNK<\/strong>&nbsp;e&nbsp;<strong>ERK1<\/strong>&nbsp;\u2192 Influencia a prolifera\u00e7\u00e3o celular, a diferencia\u00e7\u00e3o e a resposta inflamat\u00f3ria<\/li>\n\n\n\n<li><strong>Inibi\u00e7\u00e3o do NF-\u03baB<\/strong><br>Atrav\u00e9s da modula\u00e7\u00e3o de CB2 e TLR4 \u2192 reduz as citocinas pr\u00f3-inflamat\u00f3rias (TNF-\u03b1, IL-1\u03b2, IL-6)<\/li>\n\n\n\n<li><strong>Antagonismo do TLR4<\/strong><br>Suprime as vias de sinaliza\u00e7\u00e3o dependentes de MyD88\/TRIF \u2192 reduz a inflama\u00e7\u00e3o<\/li>\n\n\n\n<li><strong>Via de sinaliza\u00e7\u00e3o JAK1\/STAT1<\/strong><br>Indu\u00e7\u00e3o de genes dependentes do interfer\u00e3o \u2192 refor\u00e7a a defesa antiviral<\/li>\n\n\n\n<li><strong>Modula\u00e7\u00e3o de citocinas<\/strong><br>Aumento da IL-10 (anti-inflamat\u00f3ria), inibi\u00e7\u00e3o da IL-12 (pr\u00f3-inflamat\u00f3ria) \u2192 promove o equil\u00edbrio TH1\/TH2<\/li>\n\n\n\n<li><strong>Regula\u00e7\u00e3o das c\u00e9lulas T<\/strong><br>Promovido&nbsp;<strong>Express\u00e3o de Foxp3<\/strong>&nbsp;em c\u00e9lulas T reguladoras \u2192 efeito imunomodulador<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Kurkuma_Curcumin-2\"><\/span><strong>A\u00e7afr\u00e3o-da-terra (curcumina)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Inibi\u00e7\u00e3o do NF-\u03baB<\/strong><br>Suprime este fator de transcri\u00e7\u00e3o central \u2192 reduz a inflama\u00e7\u00e3o, a prolifera\u00e7\u00e3o celular e a inibi\u00e7\u00e3o da apoptose \u2192 diminui a express\u00e3o de COX-2, TNF-\u03b1, IL-6, IL-8, MMP-9<\/li>\n\n\n\n<li><strong>Ativa\u00e7\u00e3o do p53<\/strong><br>Aumenta o supressor de tumores p53 \u2192 favorece a repara\u00e7\u00e3o do ADN e a apoptose<\/li>\n\n\n\n<li><strong>Regula\u00e7\u00e3o do r\u00e1cio Bax\/Bcl-2<\/strong><br>Aumenta o Bax pr\u00f3-apopt\u00f3tico, diminui o Bcl-2 anti-apopt\u00f3tico \u2192 promove a apoptose mediada por mitoc\u00f4ndrias<\/li>\n\n\n\n<li><strong>Inibi\u00e7\u00e3o de mTOR<\/strong><br>Inibe o crescimento e a prolifera\u00e7\u00e3o \u2192 efeito anticarcinog\u00e9nico<\/li>\n\n\n\n<li><strong>Antiangiog\u00e9nese<\/strong><br>Inibe o VEGF \u2192 impede a forma\u00e7\u00e3o de novos vasos tumorais<\/li>\n\n\n\n<li><strong>Inibi\u00e7\u00e3o da MMP-9<\/strong><br>Reduz a degrada\u00e7\u00e3o dos tecidos \u2192 inibe a invas\u00e3o e as met\u00e1stases<\/li>\n\n\n\n<li><strong>Inibi\u00e7\u00e3o de mol\u00e9culas de ades\u00e3o (por exemplo, CD44)<\/strong><br>Impede a ades\u00e3o e a invas\u00e3o das c\u00e9lulas tumorais<\/li>\n\n\n\n<li><strong>Ativa\u00e7\u00e3o da via de sinaliza\u00e7\u00e3o Nrf2<\/strong><br>Aumenta os antioxidantes do pr\u00f3prio organismo \u2192 protege contra o stress oxidativo<\/li>\n\n\n\n<li><strong>Modula\u00e7\u00e3o das prote\u00ednas do ciclo celular<\/strong><br>Inibe a ciclina D1, p16, inibidores de CDK \u2192 paragem no ciclo celular<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Ingwer_Gingerole-2\"><\/span><strong>Gengibre (ginger\u00f3is)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Ativa\u00e7\u00e3o do recetor TRPV1<\/strong><br>Os gengibir\u00f3is ligam-se ao canal i\u00f3nico TRPV1 das c\u00e9lulas imunit\u00e1rias \u2192 p\u00f5em os granul\u00f3citos neutr\u00f3filos em alerta m\u00e1ximo \u2192 aumentam a produ\u00e7\u00e3o de ROS e a secre\u00e7\u00e3o de CXCL8 durante a estimula\u00e7\u00e3o bacteriana<\/li>\n\n\n\n<li><strong>Inibi\u00e7\u00e3o da inflama\u00e7\u00e3o<\/strong><br>Inibi\u00e7\u00e3o de&nbsp;<strong>NF-\u03baB<\/strong>,&nbsp;<strong>p38 MAPK<\/strong>&nbsp;e&nbsp;<strong>JNK<\/strong>&nbsp;\u2192 reduz a express\u00e3o de citocinas pr\u00f3-inflamat\u00f3rias (TNF-\u03b1, IL-1\u03b2, IL-6, IL-8), COX-2 e PGE2<\/li>\n\n\n\n<li><strong>Antioxidante<\/strong><br>Aumento das enzimas antioxidantes (por exemplo, SOD), prote\u00e7\u00e3o contra os danos mitocondriais<\/li>\n\n\n\n<li><strong>Antiem\u00e9tico<\/strong><br>Efeito atrav\u00e9s de vias de sinaliza\u00e7\u00e3o serotonin\u00e9rgicas e colin\u00e9rgicas no centro do v\u00f3mito \u2192 alivia as n\u00e1useas<\/li>\n\n\n\n<li><strong>Efeito metab\u00f3lico<\/strong><br>Melhora a sensibilidade \u00e0 insulina, promove a capta\u00e7\u00e3o de glicose mediada por GLUT4 \u2192 \u00fatil para a diabetes<\/li>\n\n\n\n<li><strong>Prote\u00e7\u00e3o da cartilagem<\/strong><br>A inibi\u00e7\u00e3o da via de sinaliza\u00e7\u00e3o p38\/JNK \u2192 reduz a degrada\u00e7\u00e3o da cartilagem na osteoartrite<\/li>\n\n\n\n<li><strong>Indu\u00e7\u00e3o de apoptose<\/strong><br>O 6-Shogaol induz a apoptose nas c\u00e9lulas sinoviais inflamadas \u2192 efeito anti-inflamat\u00f3rio<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Zitrusfruchte_Quercetin-2\"><\/span><strong>Citrinos e quercetina<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Inibi\u00e7\u00e3o do NF-\u03baB<\/strong><br>Bloqueia este interrutor inflamat\u00f3rio central \u2192 reduz o TNF-\u03b1, a IL-6, a IL-1\u03b2, a COX-2 e a iNOS<\/li>\n\n\n\n<li><strong>Ativa\u00e7\u00e3o de Nrf2<\/strong><br>Liga-se aos elementos de resposta antioxidante (ARE) \u2192 aumenta a express\u00e3o de HO-1, NQO1, GCLC \u2192 refor\u00e7a a defesa antioxidante end\u00f3gena<\/li>\n\n\n\n<li><strong>Modula\u00e7\u00e3o de MAPK<\/strong><br>Inibe a p38, a JNK e a ERK \u2192 regula a inflama\u00e7\u00e3o, a prolifera\u00e7\u00e3o e a apoptose<\/li>\n\n\n\n<li><strong>Inibi\u00e7\u00e3o de JAK\/STAT<\/strong><br>Suprime a sinaliza\u00e7\u00e3o pr\u00f3-inflamat\u00f3ria<\/li>\n\n\n\n<li><strong>Inibi\u00e7\u00e3o da COX-1\/2 e da LOX<\/strong><br>Reduz a forma\u00e7\u00e3o de prostaglandinas e leucotrienos \u2192 Anti-inflamat\u00f3rio<\/li>\n\n\n\n<li><strong>Ativa\u00e7\u00e3o da AMPK\/SIRT1<\/strong><br>Melhora o metabolismo mitocondrial, promove a autofagia, protege contra o stress oxidativo<\/li>\n\n\n\n<li><strong>Estabiliza\u00e7\u00e3o dos mast\u00f3citos<\/strong><br>Inibe a liberta\u00e7\u00e3o de histamina e de citocinas (por exemplo, IL-8, TNF) \u2192 anti-al\u00e9rgico<\/li>\n\n\n\n<li><strong>Atenua\u00e7\u00e3o do inflamassoma NLRP3<\/strong><br>Suprime a produ\u00e7\u00e3o de IL-1\u03b2<\/li>\n\n\n\n<li><strong>Efeito senol\u00edtico<\/strong><br>Promove a elimina\u00e7\u00e3o de c\u00e9lulas velhas e disfuncionais (senesc\u00eancia)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Schwarzkummelol_Nigella_sativa-2\"><\/span><strong>\u00d3leo de sementes de cominho preto (Nigella sativa)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Ativa\u00e7\u00e3o Nrf2\/ARE<\/strong><br>Aumenta as enzimas antioxidantes (HO-1, SOD, CAT) \u2192 protege contra o stress oxidativo<\/li>\n\n\n\n<li><strong>Inibi\u00e7\u00e3o do NF-\u03baB<\/strong><br>Suprime a inflama\u00e7\u00e3o \u2192 reduz o TNF-\u03b1, IL-6, IL-1\u03b2, COX-2, iNOS<\/li>\n\n\n\n<li><strong>Inibi\u00e7\u00e3o da PI3K\/Akt\/mTOR<\/strong><br>Inibe o crescimento e a prolifera\u00e7\u00e3o \u2192 efeito anti-carcinog\u00e9nico<\/li>\n\n\n\n<li><strong>Modula\u00e7\u00e3o de MAPK<\/strong><br>Inibe a p38, a JNK e a ERK \u2192 regula a inflama\u00e7\u00e3o e a apoptose<\/li>\n\n\n\n<li><strong>Ativa\u00e7\u00e3o da AMPK\/SIRT1<\/strong><br>Melhora o metabolismo mitocondrial, promove a autofagia<\/li>\n\n\n\n<li><strong>Indu\u00e7\u00e3o de apoptose<\/strong><br>Ativa p53, rela\u00e7\u00e3o Bax\/Bcl-2, caspases \u2192 morte celular do tumor<\/li>\n\n\n\n<li><strong>Inibi\u00e7\u00e3o da COX-2<\/strong><br>Reduz os mediadores inflamat\u00f3rios<\/li>\n\n\n\n<li><strong>Inibi\u00e7\u00e3o de JAK\/STAT<\/strong><br>Suprime a sinaliza\u00e7\u00e3o pr\u00f3-inflamat\u00f3ria<\/li>\n\n\n\n<li><strong>Aumento do GABA<\/strong><br>Aumenta os n\u00edveis cerebrais de GABA \u2192 anticonvulsivo, neuroprotector<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Ginseng_Panax_ginseng-2\"><\/span><strong>Ginseng (Panax ginseng)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Modula\u00e7\u00e3o do eixo HPA<\/strong><br>Ginsen\u00f3sidos (por exemplo.&nbsp;<strong>Estrada<\/strong>) atenuam a tens\u00e3o induzida&nbsp;<strong>Produ\u00e7\u00e3o de cortisol<\/strong>&nbsp;\u2192 efeito adaptog\u00e9nico para a exaust\u00e3o e o stress<\/li>\n\n\n\n<li><strong>Sistemas de neurotransmissores<\/strong><br>Ativar&nbsp;<strong>colin\u00e9rgico<\/strong>&nbsp;e&nbsp;<strong>vias de sinaliza\u00e7\u00e3o dopamin\u00e9rgicas<\/strong>&nbsp;\u2192 melhoram o desempenho cognitivo, a concentra\u00e7\u00e3o e o humor (por exemplo, atrav\u00e9s do ginsen\u00f3sido&nbsp;<strong>Rg1<\/strong>)<\/li>\n\n\n\n<li><strong>Inibi\u00e7\u00e3o da inflama\u00e7\u00e3o<\/strong><br>Inibi\u00e7\u00f5es&nbsp;<strong>NF-\u03baB<\/strong>&nbsp;e citocinas pr\u00f3-inflamat\u00f3rias \u2192 reduzir os processos neuroinflamat\u00f3rios<\/li>\n\n\n\n<li><strong>Efeito antioxidante<\/strong><br>Ativar&nbsp;<strong>Nrf2<\/strong>-via de sinaliza\u00e7\u00e3o \u2192 aumento dos antioxidantes end\u00f3genos (HO-1, SOD) \u2192 prote\u00e7\u00e3o contra o stress oxidativo<\/li>\n\n\n\n<li><strong>Neuroprotec\u00e7\u00e3o<\/strong><br>Transportar&nbsp;<strong>BDNF<\/strong>&nbsp;(fator neurotr\u00f3fico derivado do c\u00e9rebro) \u2192 favorece a regenera\u00e7\u00e3o neuronal e a plasticidade sin\u00e1ptica<\/li>\n\n\n\n<li><strong>Inibi\u00e7\u00e3o do amiloide \u03b2<\/strong><br>Suprimir a forma\u00e7\u00e3o de&nbsp;<strong>Placas amiloide-\u03b2<\/strong>&nbsp;\u2192 Potencialmente neuroprotector na doen\u00e7a de Alzheimer<\/li>\n\n\n\n<li><strong>Favorecer a circula\u00e7\u00e3o sangu\u00ednea<\/strong><br>Aumentar a produ\u00e7\u00e3o de&nbsp;<strong>\u00d3xido n\u00edtrico (NO)<\/strong>&nbsp;\u2192 Vasodilata\u00e7\u00e3o, melhoria da perfus\u00e3o cerebral e perif\u00e9rica<\/li>\n\n\n\n<li><strong>Imunomodula\u00e7\u00e3o<\/strong><br>Regulam a atividade dos macr\u00f3fagos e das c\u00e9lulas NK atrav\u00e9s de&nbsp;<strong>TLR4<\/strong>&nbsp;e&nbsp;<strong>MAPK<\/strong>&nbsp;\u2192 Refor\u00e7ar a defesa imunit\u00e1ria<\/li>\n<\/ul>\n\n\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"hier\"><span class=\"ez-toc-section\" id=\"Rituximab_%E2%80%93_die_Entwicklungsgeschichte\"><\/span>Rituximab - a hist\u00f3ria do desenvolvimento<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"1975_%E2%80%93_Entwicklung_der_Hybridoma-Technologie\"><\/span>1975 - Desenvolvimento do <strong>Tecnologia de hibridoma<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Antes de 1975, os investigadores n\u00e3o conseguiam encontrar grandes quantidades de <strong>anticorpo id\u00eantico<\/strong> produzir anticorpos. Quando imunizaram um rato com um antig\u00e9nio, o rato produziu um n\u00famero limitado de anticorpos diferentes contra diferentes partes do antig\u00e9nio (policlonais).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Georges K\u00f6hler<\/strong> e <strong>C\u00e9sar Milstein<\/strong> desenvolveu o <strong>Tecnologia de hibridoma<\/strong> por<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Os linf\u00f3citos B do ba\u00e7o de um rato imunizado tomaram<\/li>\n\n\n\n<li>estes com <strong>c\u00e9lulas de mieloma imortais<\/strong> (c\u00e9lulas cancerosas que se podem dividir indefinidamente) imunizados com<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Isso foi revolucion\u00e1rio<\/strong>, \u00c9 por isso que, em 1984, ambos <strong>Pr\u00e9mio Nobel da Fisiologia ou Medicina<\/strong> recebido.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Wie_konnen_Zellen_unsterblich_sein\"><\/span>Como \u00e9 que as c\u00e9lulas podem ser imortais?<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">As c\u00e9lulas tumorais s\u00e3o sempre imortais porque utilizam um truque para estimular a c\u00e9lula a dividir-se repetidamente e mant\u00eam esta capacidade de divis\u00e3o. As c\u00e9lulas normais, pelo contr\u00e1rio, morrem automaticamente, como se explica a seguir.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Plasmozytom_bei_Mausen_%E2%80%93_die_ursprungliche_Quelle\"><\/span>Plasmocitoma em ratos - a fonte original<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">As c\u00e9lulas imortais do mieloma m\u00faltiplo t\u00eam origem em plasmocitomas naturais (tumores linfomatosos) de ratinhos de ra\u00e7a pura, em particular das estirpes de ratinhos BALB\/c. Estes tumores desenvolveram-se espontaneamente ou foram induzidos por injec\u00e7\u00f5es de \u00f3leo.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Die_erste_gangige_Zelllinie_%E2%80%93_SP20\"><\/span>A primeira linha celular comum - SP2\/0<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">A primeira linha celular comum foi a SP2\/0 e foi criada em 1979. Estas c\u00e9lulas foram utilizadas por K\u00f6hler e Milstein para desenvolver a primeira tecnologia de hibridoma.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Outras linhas celulares importantes s\u00e3o<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>NSO (mieloma do rato NSO\/U)<\/li>\n\n\n\n<li>Ag8 (um mieloma de ratinho)<\/li>\n\n\n\n<li>P3\/NS1\/1-Ag4-1 (tamb\u00e9m mieloma do ratinho)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Warum_sind_Myelomzellen_unsterblich\"><\/span>Porque \u00e9 que as c\u00e9lulas do mieloma s\u00e3o imortais?<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Normale_Zellen_%E2%80%93_Das_Hayflick-Limit\"><\/span>C\u00e9lulas normais - O limite de Hayflick<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">As c\u00e9lulas normais s\u00f3 se podem dividir 50-70 vezes (limite de Hayflick, descoberto em 1961). Depois, a divis\u00e3o p\u00e1ra e a c\u00e9lula morre. A raz\u00e3o para isto \u00e9 que os tel\u00f3meros (extremidades dos cromossomas) se tornam mais curtos em cada divis\u00e3o e, ap\u00f3s um certo encurtamento, a c\u00e9lula morre (senesc\u00eancia), ou apoptose.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Visual:<\/strong><\/p>\n\n\n\n<pre class=\"wp-block-code\"><code>C\u00e9lula normal (jovem)\nTel\u00f3meros longos\n\u251c\u2500 A c\u00e9lula divide-se 1x \u2192 tel\u00f3meros mais curtos\n\u251c\u2500 A c\u00e9lula divide-se 2x \u2192 ainda mais curtos\n\u251c\u2500 ...\n\u251c\u2500 c\u00e9lula divide-se 50x \u2192 tel\u00f3meros CRITICAMENTE curtos\n\u2514\u2500 PARAR: a c\u00e9lula morre (senesc\u00eancia)<\/code><\/pre>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Krebszellen_sind_erfinderisch_%E2%80%93_aktivieren_Telomerase\"><\/span>As c\u00e9lulas cancerosas s\u00e3o inventivas - activam a telomerase<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">As c\u00e9lulas cancerosas (como as c\u00e9lulas do mieloma) libertam-se deste sistema:<\/p>\n\n\n\n<ol class=\"wp-block-list\">\n<li>Ativa\u00e7\u00e3o da telomerase, que reconstr\u00f3i os tel\u00f3meros<\/li>\n\n\n\n<li>Muta\u00e7\u00f5es no TP53 (inativa\u00e7\u00e3o do p53) que desligam o supressor de tumores<\/li>\n\n\n\n<li>outros sinais de sobreviv\u00eancia.<\/li>\n<\/ol>\n\n\n\n<pre class=\"wp-block-code\"><code>C\u00e9lula de mieloma (tumor)\n\u251c\u2500 Telomerase activada \u2190 (esta \u00e9 a chave!)\n\u251c\u2500 A c\u00e9lula divide-se 1x \u2192 Os tel\u00f3meros s\u00e3o REPARADOS\n\u251c\u2500 A c\u00e9lula divide-se 2x \u2192 Os tel\u00f3meros s\u00e3o reparados novamente\n\u251c\u2500 A c\u00e9lula divide-se 50x \u2192 Os tel\u00f3meros ainda s\u00e3o longos\n\u251c\u2500 A c\u00e9lula divide-se 1000x \u2192 ainda est\u00e1 viva\nPossibilidade de divis\u00f5es ILIMITADAS<\/code><\/pre>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Warum_Telomerase\"><\/span>Porqu\u00ea a telomerase?<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">A telomerase \u00e9 uma enzima ribonucleoproteica (constitu\u00edda por TERT = Telomerase Reverse Transcriptase e TERC = Telomerase RNA Component). Adiciona repetidamente a sequ\u00eancia TTAGGG \u00e0s extremidades dos tel\u00f3meros e repara assim o encurtamento causado pelo processo de divis\u00e3o, o que leva \u00e0 imortalidade da c\u00e9lula.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Normal:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>A telomerase est\u00e1 presente nas c\u00e9lulas normais <strong>DESLIGADO<\/strong><\/li>\n\n\n\n<li>Apenas fracamente presente nas c\u00e9lulas germinativas (espermatoz\u00f3ides, \u00f3vulos) e nas c\u00e9lulas estaminais<\/li>\n\n\n\n<li>Por conseguinte: As c\u00e9lulas normais envelhecem e morrem<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Para o cancro:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>A telomerase \u00e9 <strong>AN<\/strong> (85-95% de todas as c\u00e9lulas cancer\u00edgenas)<\/li>\n\n\n\n<li>Repara\u00e7\u00e3o constante dos tel\u00f3meros<\/li>\n\n\n\n<li>A c\u00e9lula torna-se \u201eimortal\u201c<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"TP53-Mutation_%E2%80%93_das_andere_Puzzle-Teil\"><\/span>Muta\u00e7\u00e3o TP53 - a outra pe\u00e7a do puzzle<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Mas a telomerase, por si s\u00f3, n\u00e3o \u00e9 suficiente, pois a c\u00e9lula desencadearia um ponto de controlo de senesc\u00eancia:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Quando os tel\u00f3meros se tornam criticamente curtos, o TP53 (o \u201eguardi\u00e3o do genoma\u201c) \u00e9 normalmente ativado, dizendo: \u201eParem, a c\u00e9lula est\u00e1 danificada, vamos morrer\u201c. Nas c\u00e9lulas cancerosas, o TP53 <strong>mutado<\/strong> <strong>ou inactivado<\/strong>, pelo que a c\u00e9lula ignora este comando.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Isto significa:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Tel\u00f3meros curtos \u2192 normal: p53 ativado \u2192 morte celular<\/li>\n\n\n\n<li>C\u00e9lula do mieloma m\u00faltiplo: tel\u00f3meros curtos \u2192 p53 est\u00e1 INACTIVO \u2192 a c\u00e9lula diz: \u201eN\u00e3o importa\u201c \u2192 continuar<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Wie_Myelomzellen_unsterblich_wurden\"><\/span>Como \u00e9 que as c\u00e9lulas do mieloma se tornaram imortais<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">As c\u00e9lulas do mieloma em ratinhos desenvolveram-se em v\u00e1rias etapas ao longo de d\u00e9cadas: <\/p>\n\n\n\n<ol class=\"wp-block-list\">\n<li>Um plasm\u00f3cito normal sofreu uma transloca\u00e7\u00e3o t(12;15) ou outros erros gen\u00e9ticos<\/li>\n\n\n\n<li>O gene MYC foi sobreexpresso (condutor do cancro)<\/li>\n\n\n\n<li>p53 com muta\u00e7\u00e3o<\/li>\n\n\n\n<li>A telomerase foi activada,<\/li>\n\n\n\n<li>Ap\u00f3s v\u00e1rios ciclos de impress\u00e3o selectiva, foram criadas c\u00e9lulas verdadeiramente imortais.<\/li>\n<\/ol>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Die_erste_SP20_Hybridoma-Zelle\"><\/span>A primeira c\u00e9lula de hibridoma SP2\/0<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O SP2\/0 \u00e9 origin\u00e1rio de um mieloma de ratinho. O mieloma foi isolado de um rato BALB\/c (provavelmente ap\u00f3s inje\u00e7\u00e3o de \u00f3leo). As c\u00e9lulas foram depois cultivadas e estabelecidas. T\u00eam TELOMERASE ativa e p53 defeituoso.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">O nome \u00e9 explicado por:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>SP<\/strong>&nbsp;significa&nbsp;<em>Ba\u00e7o<\/em>&nbsp;(ba\u00e7o), uma vez que as c\u00e9lulas s\u00e3o origin\u00e1rias de c\u00e9lulas do ba\u00e7o.&nbsp;<\/li>\n\n\n\n<li><strong>2<\/strong>&nbsp;refere-se \u00e0 segunda gera\u00e7\u00e3o da linha celular.&nbsp;<\/li>\n\n\n\n<li><strong>0<\/strong>&nbsp;simboliza o&nbsp;<strong>Perda da fun\u00e7\u00e3o HGPRT<\/strong>&nbsp;(atividade \u201ezero\u201c), o que causa sensibilidade HAT*.<br>* Sensibilidade das c\u00e9lulas a um&nbsp;<strong>HAT m\u00e9dio<\/strong>&nbsp;(hipoxantina-aminopterina-timidina), que \u00e9 utilizada para a sele\u00e7\u00e3o de hibridomas<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>A cr\u00edtica na altura:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Estas c\u00e9lulas s\u00e3o as pr\u00f3prias c\u00e9lulas cancerosas!<\/li>\n\n\n\n<li>Por outras palavras, as \u201ec\u00e9lulas tumorais\u201c fundem-se com as c\u00e9lulas B normais<\/li>\n\n\n\n<li>Valeu a pena considerar isso do ponto de vista \u00e9tico\/pr\u00e1tico<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>A solu\u00e7\u00e3o:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>As c\u00e9lulas foram <strong>deliberadamente erradicado<\/strong> para a produ\u00e7\u00e3o de anticorpos<\/li>\n\n\n\n<li>Produzem imunoglobulinas (porque parte da c\u00e9lula B est\u00e1 no seu interior), mas n\u00e3o produzem outros genes \u201enocivos\u201c<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Warum_keine_normale_B-Zellen\"><\/span>Porqu\u00ea a aus\u00eancia de c\u00e9lulas B normais?<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">As c\u00e9lulas B do ba\u00e7o (ou do sangue) s\u00f3 se podem dividir at\u00e9 um certo limite (limite de Hayflick). Ap\u00f3s a fus\u00e3o com as c\u00e9lulas do mieloma m\u00faltiplo, os novos \u201ehibridomas\u201c devem tamb\u00e9m poder dividir-se indefinidamente, caso contr\u00e1rio s\u00e3o in\u00fateis.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Isto significa:<\/strong><\/p>\n\n\n\n<pre class=\"wp-block-code\"><code>Experi\u00eancia 1: Apenas c\u00e9lulas B do ba\u00e7o\nProduzem anticorpos (+)\nDividem-se apenas 50x, depois morrem (-)\n\nExperi\u00eancia 2: Apenas c\u00e9lulas do mieloma m\u00faltiplo\n\u251c\u2500 Dividir-se indefinidamente (+)\nN\u00e3o produzem anticorpos espec\u00edficos (-)\n\nExperi\u00eancia 3: HIBRIDOMA (fus\u00e3o)\n\u251c\u2500 Dividir-se indefinidamente (+) (do mieloma)\nProduzir anticorpos (+) (a partir da c\u00e9lula B)\nPerfeito!  (+)<\/code><\/pre>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Die_Fusion_%E2%80%93_der_Hybridoma-Prozess\"><\/span>A fus\u00e3o - o processo de hibridoma<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">A fus\u00e3o \u00e9 feita com polietilenoglicol (PEG) ou com impulsos el\u00e9ctricos (electrofus\u00e3o). O PEG refor\u00e7a a ades\u00e3o das membranas: duas c\u00e9lulas fundem-se para formar uma c\u00e9lula com dois n\u00facleos. Ap\u00f3s a citocinese (a citocinese assegura que cada c\u00e9lula filha recebe organelos e citoplasma e pode funcionar como uma c\u00e9lula independente): Uma c\u00e9lula com material gen\u00e9tico de ambas as c\u00e9lulas progenitoras.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Visual:<\/strong><\/p>\n\n\n\n<pre class=\"wp-block-code\"><code>C\u00e9lula B (produtora de anticorpos)\n    +\nC\u00e9lula de mieloma (imortal)\n    \u2193 (PEG ou electrofus\u00e3o)\nHibridoma (ambos!)\n    \u251c\u2500 Imortalizada (a partir do mieloma)\n    \u2514\u2500 Produz anticorpos (a partir de c\u00e9lula B)<\/code><\/pre>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Warum_Zellen_eines_Myeloms_und_nicht_anderer_Tumore\"><\/span>Porqu\u00ea c\u00e9lulas de mieloma e n\u00e3o de outros tumores?<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">As c\u00e9lulas de mieloma (linfomas de c\u00e9lulas plasm\u00e1ticas) foram escolhidas porque:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>dividem-se rapidamente (elevada taxa de prolifera\u00e7\u00e3o)<\/li>\n\n\n\n<li>s\u00e3o geneticamente est\u00e1veis (sem muitas outras muta\u00e7\u00f5es)<\/li>\n\n\n\n<li>pode rejeitar anticorpos n\u00e3o produtivos (press\u00e3o de sele\u00e7\u00e3o)<\/li>\n\n\n\n<li>j\u00e1 s\u00e3o especializados na secre\u00e7\u00e3o de prote\u00ednas (produzem anticorpos)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Outros tipos de cancro n\u00e3o teriam funcionado, por exemplo<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Cancro da pr\u00f3stata - N\u00e3o especializado na secre\u00e7\u00e3o de prote\u00ednas<\/li>\n\n\n\n<li>Melanoma - demasiadas outras muta\u00e7\u00f5es<\/li>\n\n\n\n<li>Carcinoma hepatocelular - sem produ\u00e7\u00e3o de anticorpos<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Das_Paradoxe_%E2%80%93_Krebszellen_als_Mittel_gegen_Krebs\"><\/span>O paradoxo - as c\u00e9lulas cancerosas como rem\u00e9dio para o cancro<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">A beleza e o paradoxo da tecnologia dos hibridomas: <strong>As c\u00e9lulas cancerosas (mieloma) s\u00e3o utilizadas para produzir medicamentos contra o cancro (linfoma)!<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">As c\u00e9lulas do mieloma s\u00e3o, elas pr\u00f3prias, um tipo de cancro, mas ao fundirem-se com as c\u00e9lulas B tornam-se um local de produ\u00e7\u00e3o terap\u00eautica de anticorpos monoclonais.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Neuere_Alternativen\"><\/span>Novas alternativas<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Atualmente, as c\u00e9lulas do mieloma s\u00e3o utilizadas com menos frequ\u00eancia, mas sim<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Linhas celulares humanizadas (por exemplo, CHO = c\u00e9lulas de ov\u00e1rio de hamster chin\u00eas)<\/li>\n\n\n\n<li>Tecnologias de visualiza\u00e7\u00e3o (visualiza\u00e7\u00e3o de fagos, visualiza\u00e7\u00e3o de leveduras)<\/li>\n\n\n\n<li>Mutag\u00e9nese in vitro em vez de imuniza\u00e7\u00e3o animal.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Porqu\u00ea a mudan\u00e7a?<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li> (+) Sem contamina\u00e7\u00e3o de c\u00e9lulas de mieloma<\/li>\n\n\n\n<li> (+) Mais direto do que os anticorpos quim\u00e9ricos<\/li>\n\n\n\n<li> (+) Eticamente mais limpo<\/li>\n\n\n\n<li> (+) Mais r\u00e1pido<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Em 1990, a tecnologia de hibridoma com c\u00e9lulas de mieloma para rituximab foi a <strong>\u00fanica solu\u00e7\u00e3o pr\u00e1tica dispon\u00edvel<\/strong>.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Zusammenfassung-2\"><\/span>Resumo<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><thead><tr><th>Quest\u00e3o<\/th><th>Resposta<\/th><\/tr><\/thead><tbody><tr><td><strong>De onde vieram as c\u00e9lulas do mieloma m\u00faltiplo?<\/strong><\/td><td>Linfomas espont\u00e2neos ou induzidos por \u00f3leo em ratinhos<\/td><\/tr><tr><td><strong>Que linha?<\/strong><\/td><td>SP2\/0, NSO, Ag8 (todas as linhas celulares de mieloma de ratinho)<\/td><\/tr><tr><td><strong>Porqu\u00ea imortal?<\/strong><\/td><td>Telomerase ativa + p53 com muta\u00e7\u00e3o = limite de Hayflick ultrapassado<\/td><\/tr><tr><td><strong>Como \u00e9 que a telomerase funciona?<\/strong><\/td><td>As enzimas TERT + TERC reparam incessantemente os tel\u00f3meros<\/td><\/tr><tr><td><strong>Porque n\u00e3o apenas c\u00e9lulas B?<\/strong><\/td><td>Morreria ao fim de 50 divis\u00f5es (limite de Hayflick)<\/td><\/tr><tr><td><strong>Porque n\u00e3o apenas o mieloma m\u00faltiplo?<\/strong><\/td><td>N\u00e3o produziria anticorpos<\/td><\/tr><tr><td><strong>Porqu\u00ea a fus\u00e3o?<\/strong><\/td><td>O melhor de dois mundos: imortalidade + produ\u00e7\u00e3o de anticorpos<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"1980_%E2%80%93_Entdeckung_des_Oberflachenproteins_CD20\"><\/span>1980 - Descoberta da prote\u00edna de superf\u00edcie CD20<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Lee Nadler<\/strong> do <strong>Instituto do Cancro Dana Farber<\/strong> em Boston, descobriu a prote\u00edna de superf\u00edcie CD20 como um marcador de superf\u00edcie dos linf\u00f3citos B.<br>Utilizou a nova tecnologia de hibridoma para produzir anticorpos contra marcadores de c\u00e9lulas B. Identificou o CD20 como:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Uma prote\u00edna na superf\u00edcie de todas as c\u00e9lulas B<\/li>\n\n\n\n<li>Tamb\u00e9m presente em c\u00e9lulas de linfoma de c\u00e9lulas B<\/li>\n\n\n\n<li>Um potencial alvo terap\u00eautico<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Erstes_Experiment\"><\/span>Primeira experi\u00eancia<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Testou um anticorpo anti-CD20 de murino (rato) em doentes com linfoma. O resultado foi fraco, mas constituiu a primeira prova de conceito de que \u00e9 poss\u00edvel selecionar o CD20.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Das_chimare_Antikorper-Problem\"><\/span>O problema dos anticorpos quim\u00e9ricos<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O anticorpo de Nadler e outras equipas de investiga\u00e7\u00e3o tinham anticorpos murinos (de ratinho) contra o CD20, mas havia dois problemas cr\u00edticos:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Problema 1: HAMA (Human Anti-Mouse Antibodies)<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>O corpo humano reconheceu o anticorpo do rato como \u201eestranho\u201c<\/li>\n\n\n\n<li>O doente formou anticorpos contra o anticorpo<\/li>\n\n\n\n<li>O anticorpo do rato foi neutralizado ap\u00f3s algumas infus\u00f5es<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Problema 2: Fraca efic\u00e1cia<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>A parte Fc do rato (regi\u00e3o constante) activou o sistema imunit\u00e1rio humano de forma insuficiente<\/li>\n\n\n\n<li>A IgG de ratinho n\u00e3o se liga de forma \u00f3ptima aos receptores Fc humanos<\/li>\n\n\n\n<li>A IgG de ratinho n\u00e3o ativa de forma \u00f3ptima o complemento humano<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>A solu\u00e7\u00e3o<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Os geneticistas tiveram a ideia<strong> para combinar a parte do rato (regi\u00e3o vari\u00e1vel) com a regi\u00e3o humana (regi\u00e3o constante):<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Regi\u00e3o vari\u00e1vel (parte Fab)<\/strong> - Rato<br>Esta \u00e9 a parte que reconhece o CD20<br>Os anticorpos de ratinho t\u00eam segmentos de genes especiais que podem reconhecer o CD20 muito especificamente<\/li>\n\n\n\n<li><strong>Regi\u00e3o constante (parte Fc)<\/strong> - Humano<br>Esta \u00e9 a parte que ativa o sistema imunit\u00e1rio<br>As regi\u00f5es Fc humanas ligam-se perfeitamente aos receptores Fc humanos<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Resultado: o anticorpo monoclonal quim\u00e9rico<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Suficientemente espec\u00edfico (devido \u00e0 parte do reconhecimento do rato)<\/li>\n\n\n\n<li>Suficientemente eficaz (devido \u00e0 fun\u00e7\u00e3o efectora humana)<\/li>\n\n\n\n<li>Menos problemas HAMA (porque mais humanos)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"1990-1992_%E2%80%93_Rituximab-Entwicklung\"><\/span>1990-1992 - Desenvolvimento do Rituximab<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Das_IDEC-Team\"><\/span>A equipa do IDEC<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Uma empresa de biotecnologia chamada <strong>Produtos farmac\u00eauticos IDEC<\/strong> (fundada em 1990) come\u00e7ou a trabalhar em anticorpos CD20. Pretendiam<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Procurar anticorpos murinos contra CD20<\/li>\n\n\n\n<li>em anticorpos quim\u00e9ricos<\/li>\n\n\n\n<li>testar se funcionam melhor do que as tentativas anteriores de Nadler<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Entwicklung\"><\/span>Desenvolvimento<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>1. imuniza\u00e7\u00e3o de ratinhos<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Os ratinhos foram imunizados com linhas de c\u00e9lulas B humanas<\/li>\n\n\n\n<li>O sistema imunit\u00e1rio do rato reconheceu: \u201eEstas s\u00e3o c\u00e9lulas estranhas, produzam anticorpos contra elas!\u2018<\/li>\n\n\n\n<li>Os hibridomas foram obtidos a partir das c\u00e9lulas de splice do ratinho por fus\u00e3o com as c\u00e9lulas do mieloma<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>2. rastreio<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>O melhor foi selecionado entre milhares de hibridomas<\/li>\n\n\n\n<li>Qual deles reconhece o CD20 de forma muito selectiva?<\/li>\n\n\n\n<li>Deve ser um anticorpo IgG1 forte (o melhor is\u00f3tipo para ADCC e CDC)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>3. quimeriza\u00e7\u00e3o<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>O melhor gene de anticorpo murino foi obtido<\/li>\n\n\n\n<li>A regi\u00e3o vari\u00e1vel (que reconhece o antig\u00e9nio) permaneceu murina<\/li>\n\n\n\n<li>A regi\u00e3o constante (IgG1-Fc) foi substitu\u00edda por<\/li>\n\n\n\n<li>Resultado: <strong>C2B8<\/strong> (anticorpo quim\u00e9rico #2, antig\u00e9nio de c\u00e9lulas B #8)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>4. produ\u00e7\u00e3o<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>O gene do rituximab foi encontrado em <strong>C\u00e9lulas CHO<\/strong> (Ov\u00e1rio de hamster chin\u00eas) inserido<\/li>\n\n\n\n<li>Estas c\u00e9lulas produziram Rituximab em bioreactores<\/li>\n\n\n\n<li>Os lotes podem ser limpos para garantir a qualidade m\u00e9dica<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"1993-1997_%E2%80%93_Klinische_Tests\"><\/span>1993-1997 - Ensaios cl\u00ednicos<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"1994_%E2%80%93_Phase-I-Studie\"><\/span>1994 - Estudo de fase I<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">O primeiro documento sobre os ensaios cl\u00ednicos do Rituximab:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Reff, M. E., et al. (1994).<\/strong> \u201e<a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S000649712077669X?via%3Dihub\" target=\"_blank\" rel=\"noreferrer noopener\">Deple\u00e7\u00e3o de c\u00e9lulas B in vivo por um anticorpo monoclonal humano de ratinho quim\u00e9rico para CD20<\/a>\u201e<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Este estudo mostrou:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>15 doentes com linfoma de c\u00e9lulas B refrat\u00e1rio (que n\u00e3o responde \u00e0 quimioterapia padr\u00e3o)<\/li>\n\n\n\n<li>O rituximab foi administrado em doses de 10 a 500 mg\/m\u00b2<\/li>\n\n\n\n<li><strong>Resultado:<\/strong> 6 de 15 doentes (40%) tiveram remiss\u00f5es objectivas<\/li>\n\n\n\n<li><strong>Efeitos secund\u00e1rios:<\/strong> Surpreendentemente suave para uma terapia t\u00e3o eficaz<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Foi sensacional<\/strong> - um anticorpo SOZINHO (sem quimioterapia!) foi eficaz contra o linfoma!<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"1997_%E2%80%93_Phase-II-Studie\"><\/span>1997 - Estudo de fase II<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Um estudo maior de 166 doentes com linfoma refrat\u00e1rio:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>McLaughlin, P., et al. (1998).<\/strong> \u201e<a href=\"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.1998.16.8.2825\" target=\"_blank\" rel=\"noreferrer noopener\">Terapia com anticorpo monoclonal anti-CD20 quim\u00e9rico rituximab para linfomas indolentes recidivantes: metade dos doentes responde a um programa de tratamento de quatro doses<\/a>\u201e<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Resultado:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>48% dos doentes tiveram uma remiss\u00e3o objetiva<\/li>\n\n\n\n<li>Alguns tiveram remiss\u00f5es completas que duraram muito tempo<\/li>\n\n\n\n<li>A taxa de resposta foi mais elevada do que nos dados hist\u00f3ricos com quimioterapia isolada<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"1997_%E2%80%93_FDA-Zulassung_November\"><\/span>1997 - Aprova\u00e7\u00e3o da FDA (novembro)<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Com base nos dados da Fase I e da Fase II, o IDEC apresentou um <strong>Pedido de licen\u00e7a biol\u00f3gica (BLA)<\/strong> \u00e0 FDA. Em <strong>26 de novembro de 1997<\/strong> Rituximab (com o nome <strong>Rituxan<\/strong>) aprovado pela FDA.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Foi um marco importante:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Primeiro anticorpo monoclonal para oncologia<\/strong><\/li>\n\n\n\n<li>Outros vieram mais tarde (trastuzumab para o cancro da mama em 1998, etc.).<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Warum_genau_dieser_Maus-Antikorper\"><\/span>Porqu\u00ea exatamente este anticorpo de rato?<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">O CD20 \u00e9 uma prote\u00edna de superf\u00edcie com uma estrutura 3D reconhecida pelo anticorpo de hibridoma IDEC. Os sistemas imunit\u00e1rios dos ratos t\u00eam genes V (genes de regi\u00e3o vari\u00e1vel) diferentes dos humanos. Isto significa que os anticorpos de ratinho podem, por vezes, reconhecer estruturas que os anticorpos humanos n\u00e3o reconhecem.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Por que raz\u00e3o n\u00e3o foi desenvolvido diretamente um anticorpo humanizado?<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Em 1990, isso era tecnicamente muito dif\u00edcil:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>A humaniza\u00e7\u00e3o requer o transplante de CDRs (regi\u00f5es determinantes da complementaridade) murinas para regi\u00f5es-quadro humanas<\/li>\n\n\n\n<li>Isso era poss\u00edvel, mas complexo<\/li>\n\n\n\n<li>Os anticorpos quim\u00e9ricos eram mais r\u00e1pidos e pr\u00e1ticos<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>A fus\u00e3o combina o melhor:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Da c\u00e9lula B: capacidade de produzir anticorpos espec\u00edficos<\/li>\n\n\n\n<li>Do mieloma m\u00faltiplo: capacidade ilimitada de divis\u00e3o<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Seit_1997\"><\/span>Desde 1997<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>O rituximab tornou-se o tratamento padr\u00e3o para o linfoma n\u00e3o-Hodgkin<\/li>\n\n\n\n<li>Posteriormente aprovado para a artrite reumatoide e outras indica\u00e7\u00f5es<\/li>\n\n\n\n<li>Os bi\u00f3logos chamaram-lhe \u201e<strong>O primeiro milagre anticorpo da medicina moderna<\/strong>\u201e<\/li>\n<\/ul>\n\n\n\n<div style=\"height:100px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Dosierungsempfehlungen\"><\/span>Recomenda\u00e7\u00f5es de dosagem<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\">Todas as recomenda\u00e7\u00f5es devem ser consideradas exclusivamente como uma base para discuss\u00e3o com os m\u00e9dicos respons\u00e1veis pelo tratamento, em particular os oncologistas, e n\u00e3o representam uma indica\u00e7\u00e3o de dosagem geralmente v\u00e1lida.<\/p>\n<\/blockquote>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Fur_ABC-DLBCL\"><\/span>Para DLBCL-ABC<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">As dosagens de Huaier N\u00c3O dependem fundamentalmente do peso corporal e, como tal, geralmente n\u00e3o requerem ajuste, uma vez que o efeito n\u00e3o depende da concentra\u00e7\u00e3o no sangue (como os antibi\u00f3ticos) mas sim de vias de sinaliza\u00e7\u00e3o que induzem os efeitos pretendidos.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>FL com t(14;18)<\/strong><br>PI3K\/AKT-dominante \u2192 Huaier ideal <\/li>\n\n\n\n<li><strong>DLBCL ABC<\/strong><br>NF-\u03baB-dominante \u2192 Huaier + curcumina ideal <\/li>\n\n\n\n<li><strong>DLBCL-GCB<\/strong><br>BCL2-dominante \u2192 semelhante \u00e0 FL <\/li>\n\n\n\n<li><strong>Burkitt<\/strong><br>Inibidores de MYC \u2192 mTOR (sulforafano, berberina)<\/li>\n<\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img decoding=\"async\" width=\"1024\" height=\"457\" src=\"https:\/\/csiag.de\/wp-content\/uploads\/2026\/03\/image-1024x457.png\" alt=\"\" class=\"wp-image-13116\" srcset=\"https:\/\/csiag.de\/wp-content\/uploads\/2026\/03\/image-1024x457.png 1024w, https:\/\/csiag.de\/wp-content\/uploads\/2026\/03\/image-300x134.png 300w, https:\/\/csiag.de\/wp-content\/uploads\/2026\/03\/image-768x343.png 768w, https:\/\/csiag.de\/wp-content\/uploads\/2026\/03\/image-18x8.png 18w, https:\/\/csiag.de\/wp-content\/uploads\/2026\/03\/image.png 1280w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">... ser\u00e1 continuado ...<\/p>","protected":false},"excerpt":{"rendered":"<p>Es gibt dutzende Arten Lymphome. Nicht jede Art spricht auf jede Therapie an, u.U. kann eine Therapie f\u00fcr eine bestimmte Lymphomart sogar kontraproduktiv sein. Diese \u00dcbersicht soll einerseits eine solide Diagnostik unterst\u00fctzen, andererseits auch spezifische, je nach Lymphomart und Subtyp geeignete &#8211; pflanzlich ausgerichtete &#8211; Therapiem\u00f6glichkeiten zur Diskussion stellen. Soweit klinische Studien zu einer adjuvanten&hellip;&nbsp;<a href=\"https:\/\/csiag.de\/pt\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/\" rel=\"bookmark\">Ler mais \"<span class=\"screen-reader-text\">Linfoma - op\u00e7\u00f5es terap\u00eauticas<\/span><\/a><\/p>","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_lmt_disableupdate":"","_lmt_disable":"","neve_meta_sidebar":"","neve_meta_container":"","neve_meta_enable_content_width":"","neve_meta_content_width":0,"neve_meta_title_alignment":"","neve_meta_author_avatar":"","neve_post_elements_order":"","neve_meta_disable_header":"","neve_meta_disable_footer":"","neve_meta_disable_title":"","footnotes":""},"categories":[5584,1078,354],"tags":[],"class_list":["post-12877","post","type-post","status-publish","format-standard","hentry","category-krebs","category-medizin","category-medizin-gesundheit"],"acf":[],"modified_by":"Achim Goerner","_links":{"self":[{"href":"https:\/\/csiag.de\/pt\/wp-json\/wp\/v2\/posts\/12877","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/csiag.de\/pt\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csiag.de\/pt\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csiag.de\/pt\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/csiag.de\/pt\/wp-json\/wp\/v2\/comments?post=12877"}],"version-history":[{"count":1,"href":"https:\/\/csiag.de\/pt\/wp-json\/wp\/v2\/posts\/12877\/revisions"}],"predecessor-version":[{"id":13625,"href":"https:\/\/csiag.de\/pt\/wp-json\/wp\/v2\/posts\/12877\/revisions\/13625"}],"wp:attachment":[{"href":"https:\/\/csiag.de\/pt\/wp-json\/wp\/v2\/media?parent=12877"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csiag.de\/pt\/wp-json\/wp\/v2\/categories?post=12877"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csiag.de\/pt\/wp-json\/wp\/v2\/tags?post=12877"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}