{"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":"lymphoma-treatment-options","status":"publish","type":"post","link":"https:\/\/csiag.de\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/","title":{"rendered":"Lymphoma - treatment options"},"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\">Table of contents<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Wie_entstehen_Lymphom-Erkrankungen\" >How do lymphoma diseases develop?<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Einleitung\" >Introduction<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Ubersicht_der_Lymphomarten\" >Overview of lymphoma types<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Hodgkin-Lymphom_ca_10-15_aller_Lymphome\" >Hodgkin's lymphoma (approx. 10-15% of all lymphomas)<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klassisches_Hodgkin-Lymphom_cHL\" >Classical Hodgkin's lymphoma (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Nodulares_Lymphozyten-dominantes_HL_NLPHL\" >Nodular lymphocyte-dominant HL (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Non-Hodgkin-Lymphome_NHL_ca_85-90\" >Non-Hodgkin's lymphoma (NHL, approx. 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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#B-Zell-Lymphome_80_aller_NHL\" >B-cell lymphomas (80% of all NHL)<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Indolente_niedrig-maligne_B-Zell-Lymphome\" >Indolent (low-malignant) B-cell lymphomas:<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Aggressive_B-Zell-Lymphome\" >Aggressive B-cell lymphomas:<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#GrauzonenGrenzfalle\" >Gray areas\/borderline cases:<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Spezielle_extranoduale_Lymphome\" >Special extranodal lymphomas:<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#T-Zell-_und_NK-Zell-Lymphome_20_aller_NHL\" >T-cell and NK-cell lymphomas (20% of all NHL)<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Periphere_T-Zell-Lymphome_PTCL\" >Peripheral T-cell lymphomas (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Kutane_T-Zell-Lymphome\" >Cutaneous T-cell lymphomas:<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Lymphoblastische_Lymphome\" >Lymphoblastic lymphomas:<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#NK-Zell-Lymphome\" >NK cell lymphomas:<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Hodgkin-Lymphom_%E2%80%93_Verwandte_Erkrankungen\" >Hodgkin's lymphoma - Related diseases<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Immunproliferative_Erkrankungen_Grenzfalle\" >Immunoproliferative diseases &amp; borderline cases<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Epidemiologische_Ubersicht\" >Epidemiological overview<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klassifikation_nach_Biologie_Prognose\" >Classification according to biology (prognosis)<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differentielle_Darstellung_%E2%80%93_Non-Hodgkin-Lymphome\" >Differential presentation - Non-Hodgkin's lymphomas<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Follikulares_Lymphom_FL\" >Follicular lymphoma (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Lymphoplasmozytisches_Lymphom_%E2%80%93_Waldenstrom-Makroglobulinamie\" >Lymphoplasmocytic lymphoma - Waldenstr\u00f6m's macroglobulinemia<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisch-morphologische_Merkmale\" >Clinical-morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methoden\" >Diagnostic methods<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Kleines_lymphozytische_Leukamie_Lymphom_CLLSLL\" >Small lymphocytic leukemia \/ lymphoma (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Merkmale\" >Clinical features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-2\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Kriterien_nach_IWCLL\" >Diagnostic criteria (according to 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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnosen\" >Differential diagnoses<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methoden-2\" >Diagnostic methods<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-2\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-2\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Indikation_zur_Therapie_nach_iwCLLOnkopedia\" >Indication for therapy (according to 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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Behandlungsoptionen\" >Treatment options<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Marginalzonen-Lymphome\" >Marginal zone lymphomas<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Extranodales_Marginalzonen-Lymphom_MALT-Lymphom\" >Extranodal marginal zone lymphoma (MALT lymphoma)<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-3\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnosemethodik\" >Diagnostic methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie_und_Prognose\" >Therapy and prognosis<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Nodales_Marginalzonen-Lymphom_nMZL\" >Nodal marginal zone lymphoma (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Merkmale-2\" >Clinical features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzierung_vom_splenischen_und_extranodalen_MZL\" >Differentiation between splenic and extranodal MZL<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzierung_von_anderen_indolenten_B-Zell-Lymphomen\" >Differentiation from other indolent B-cell lymphomas<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnosemethodik-2\" >Diagnostic methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-3\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Splenisches_Marginalzonen-Lymphom_SMZL\" >Splenic marginal zone lymphoma (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Merkmale-3\" >Clinical features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Zytomorphologie\" >Cytomorphology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Histologie\" >Histology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Immunphanotyp\" >Immunophenotype<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Zytogenetik_und_molekulare_Marker\" >Cytogenetics and molecular markers<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-4\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnosemethodik-3\" >Diagnostic methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie_und_Prognose-2\" >Therapy and prognosis<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Primar_kutane_Lymphome_CL\" >Primary cutaneous lymphomas (CL)<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisch-morphologische_Merkmale-2\" >Clinical-morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnose\" >Differential diagnosis<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methoden-3\" >Diagnostic methods<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-4\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-3\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Primar_duodenales_B-Zell-Lymphom_MALT-Typ\" >Primary duodenal B-cell lymphoma (MALT type)<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Merkmale-4\" >Clinical features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-5\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methoden-4\" >Diagnostic methods<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-5\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-4\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisch-morphologische_Merkmale-3\" >Clinical-morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diffus_Groszelliges_B-Zell-Lymphom_DLBCL\" >Diffuse large B-cell lymphoma (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Molekulare_Subtypen_Cell_of_Origin_COO\" >Molecular subtypes (Cell of Origin, 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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Merkmale-5\" >Clinical features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostische_Abgrenzung\" >Differential diagnosis<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Kriterien\" >Diagnostic criteria<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie_und_Prognose-3\" >Therapy and prognosis<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Primar_mediastinales_B-Zell-Lymphom_pMBCL\" >Primary mediastinal B-cell lymphoma (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Prasentation\" >Clinical presentation<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Pathogenese_und_Diagnostik\" >Pathogenesis and diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie_und_Prognose-4\" >Therapy and prognosis<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-6\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Burkitt-Lymphom_BL\" >Burkitt's lymphoma (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Merkmale-6\" >Clinical features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-7\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methoden-5\" >Diagnostic methods<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-6\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-5\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Lymphoblastisches_Lymphom_BL\" >Lymphoblastic lymphoma (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisch-morphologische_Merkmale-4\" >Clinical-morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-8\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methoden-6\" >Diagnostic methods<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-7\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-6\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Primar_kutanes_diffus_groszelliges_B-Zell-Lymphom_Beintyp_DLBCL_LT\" >Primary cutaneous diffuse large B-cell lymphoma, leg type (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Merkmale-7\" >Clinical features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisch-morphologische_Merkmale-5\" >Clinical-morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-9\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methoden-7\" >Diagnostic methods<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-8\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-7\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#GrauzonenGrenzfalle-2\" >Gray areas\/borderline cases<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diffus_groszelliges_B-Zell-Lymphom_NOS_DLBCL_NOS_und_Burkitt-Lymphom_BL\" >Diffuse large B-cell lymphoma, NOS (DLBCL, NOS) and Burkitt's lymphoma (BL)<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_und_morphologisches_Bild\" >Clinical and Morphological Picture<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_Methodik\" >Differential Diagnosis and Methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-9\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-8\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Spezielle_extranoduale_Lymphome-2\" >Extranodal lymphomas<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Hepatosplenisches_Lymphom_HSTL\" >Hepatosplenic lymphoma (HSTL)<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Merkmale-8\" >Clinical features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-10\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methoden-8\" >Diagnostic methods<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie_und_Prognose-5\" >Therapy and prognosis<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Intravaszulares_groszelliges_B-Zell-Lymphom\" >Intravascular large B-cell lymphoma<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Merkmale-9\" >Clinical features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostik\" >Diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-11\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie_und_Prognose-6\" >Therapy and prognosis<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Primar_Effusions-Lymphom_PEL\" >Primary effusion lymphoma (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-12\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_und_immunophanotypische_Unterscheidung\" >Clinical and immunophenotypic differentiation<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#HHV8-Assoziiiertes_Lymphom\" >HHV8-associated lymphoma<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-13\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_und_histologische_Merkmale\" >Clinical and histological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_zu_anderen_Lymphomen\" >Differential diagnosis to other lymphomas<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#T-Zell-_und_NK-Zell-Lymphome\" >T-cell and NK-cell lymphomas<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Peripheres_T-Zell-Lymphom_PTCL-NOS\" >Peripheral T-cell lymphoma (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisch-morphologische_Merkmale-6\" >Clinical-morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-14\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methoden-9\" >Diagnostic methods<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-10\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-9\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Angioimmunoblastisches_T-Zell-Lymphom_AITL\" >Angioimmunoblastic T-cell lymphoma (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_Merkmale_und_morphologische_Zeichen\" >Clinical features and morphological signs<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnose-2\" >Differential diagnosis<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methodik\" >Diagnostic Methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-11\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-10\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Follikulares_T-Zell-Lymphom_PTFCL\" >Cutaneous T-cell lymphoma<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisch-morphologische_Merkmale-7\" >Clinical-morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik\" >Differential diagnosis and methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-12\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-11\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Hepatosplenisches_T-Zell-Lymphom_%CE%B3%CE%B4-Typ\" >Hepatosplenic T-cell lymphoma (\u03b3\u03b4-type)<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinische_und_klinisch-morphologische_Merkmale\" >Clinical and clinicomorphological characteristics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik-2\" >Differential diagnosis and methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-13\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-12\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Enteropathie-assoziiertes_T-Zell-Lymphom_EATL\" >Enteropathy-associated T-cell lymphoma (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild\" >Clinical picture<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Morphologische_Merkmale\" >Morphological characteristics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-15\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methodik-2\" >Diagnostic Methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-14\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-13\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Anaplastisches_groszelliges_Lymphom_ALCL\" >Anaplastic large cell lymphoma (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild-2\" >Clinical picture<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Morphologie\" >Morphology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-16\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-15\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-14\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Mycosis_fungoides\" >Mycosis fungoides<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_klinisch-morphologische_Merkmale\" >Clinical picture and clinical-morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik-3\" >Differential diagnosis and methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-16\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-15\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Sezary-Syndrom\" >S\u00e9zary syndrome<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild-3\" >Clinical picture<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Morphologie-2\" >Morphology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-17\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methodik-3\" >Diagnostic Methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-17\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-16\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Primar_kutanes_anaplastisches_groszelliges_CD30-positives_Lymphom_cALCL\" >Primary cutaneous anaplastic large cell CD30-positive lymphoma (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_und_morphologisches_Bild-2\" >Clinical and Morphological Picture<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik-4\" >Differential diagnosis and methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-18\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-17\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Kutanes_Marginalzonen-Lymphom\" >Cutaneous marginal zone lymphoma<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_klinisch-morphologische_Merkmale-2\" >Clinical picture and clinical-morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik-5\" >Differential diagnosis and methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostik-2\" >Diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-19\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-18\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Kutanes_Lymphom_mit_korniger_Mittelfingertatowierung\" >Cutaneous lymphoma with granular middle finger tattoo<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_klinisch-morphologische_Merkmale-3\" >Clinical picture and clinical-morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnose_und_Diagnostik\" >Differential diagnosis and diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostikmethodik\" >Diagnostic Methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-20\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-19\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#B-lymphoblastisches_LymphomLeukamie_B-ALL\" >B-lymphoblastic lymphoma\/leukemia (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_klinisch-morphologische_Merkmale-4\" >Clinical picture and clinical-morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-18\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostikmethoden\" >Diagnostic methods<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-21\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-20\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#T-lymphoblastisches_LymphomLeukamie_T-ALL\" >T-lymphoblastic lymphoma\/leukemia (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisch-morphologische_Merkmale-8\" >Clinical-morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-19\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostik-3\" >Diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-22\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-21\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#NK-Zell-Lymphome-2\" >NK-cell lymphomas<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Extranodales_NK-Zell-Lymphom\" >Extranodal NK cell lymphoma<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_morphologische_Merkmale\" >Clinical picture and morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-20\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostikmethodik-2\" >Diagnostic Methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-23\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-22\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Agressive_NK-Zell-Leukamie_ANKL\" >Aggressive NK-cell leukemia (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_und_morphologisches_Bild-3\" >Clinical and Morphological Picture<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik-6\" >Differential diagnosis and methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnosen-2\" >Differential diagnoses<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostische_Methodik-4\" >Diagnostic Methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-24\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-23\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Chronische_NK-Zell-Leukamie\" >Chronic NK cell leukemia<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_klinisch-morphologische_Merkmale-5\" >Clinical picture and clinical-morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik-7\" >Differential diagnosis and methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-25\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-24\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Hodgkin-Lymphom_%E2%80%93_Verwandte_Erkrankungen-2\" >Hodgkin's lymphoma - Related diseases<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Nodulares_lymphozytenpradominantes_Hodgkin-Lymphom_NLPHL\" >Nodular lymphocyte predominant Hodgkin lymphoma (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_und_morphologisches_Bild-4\" >Clinical and Morphological Picture<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik-8\" >Differential diagnosis and methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostik-4\" >Diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-26\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-25\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#EBV-positives_diffuses_groszelliges_B-Zell-Lymphom_PTLD\" >EBV-positive Diffuse Large B-cell Lymphoma (PTLD)<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_und_morphologisches_Bild-5\" >Clinical and Morphological Picture<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-21\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostik-5\" >Diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-27\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-26\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Immunproliferative_Erkrankungen_Grenzfalle-2\" >Immunoproliferative diseases &amp; borderline cases<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#MALT-Lymphome\" >MALT lymphomas<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_morphologische_Merkmale-2\" >Clinical picture and morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_Diagnostik\" >Differential diagnosis and diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-28\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#MALT-Lymphom\" >MALT lymphoma<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Posttransplantationale_lymphoproliferative_Storung_PTLD\" >Post-transplant lymphoproliferative disorder (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-27\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#MALT-Lymphom-2\" >MALT lymphoma<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#PTLD\" >Post-transplant lymphoproliferative disorder<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Zusammenfassung\" >Summary<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Lymphomatoide_Granulomatose\" >Lymphomatoid granulomatosis<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_klinisch-morphologische_Merkmale-6\" >Clinical picture and clinical-morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik-9\" >Differential diagnosis and methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-29\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-28\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Granulomatose_mit_organerhaltender_Vaskulitis_GANZL\" >Granulomatosis with organ-preserving vasculitis (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_klinisch-morphologische_Merkmale-7\" >Clinical picture and clinical-morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnose_und_-methodik\" >Differential diagnosis and methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-30\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-29\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#EBV-assoziierte_B-Zell-Lymphoproliferationen\" >EBV-associated B-cell lymphoproliferations<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_morphologische_Merkmale-3\" >Clinical picture and morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_Methodik-2\" >Differential Diagnosis and Methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-31\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-30\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#PTLD-2\" >Post-transplant lymphoproliferative disorder<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#EBV_DLBCL_des_alteren_Menschen\" >EBV+ DLBCL in the elderly<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Primar_kutanes_DLBCL_untere_Extremitat\" >Primary cutaneous DLBCL, lower extremity<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Hodgkin-Lymphom\" >Hodgkin's lymphoma<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klassisches_Hodgkin-Lymphom_nodulare_Sklerose_cHL_NS\" >Classical Hodgkin's lymphoma, nodular sclerosis (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild-4\" >Clinical picture<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisch-morphologische_Merkmale-9\" >Clinical-morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik-22\" >Differential diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostik-6\" >Diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-32\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Stadienadaptierte_Therapie\" >Stage-adapted therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-31\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klassisches_Hodgkin-Lymphom_cHL_%E2%80%93_gemischte_Zellularitat_MC\" >Classical Hodgkin's lymphoma (cHL) - mixed cellularity (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_morphologische_Merkmale-4\" >Clinical picture and morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnose_und_-methodik-2\" >Differential diagnosis and methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie_und_Prognose-7\" >Therapy and prognosis<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klassisches_Hodgkin-Lymphom_%E2%80%93_lymphozytenreicher_Typ_cHL_LR\" >Classical Hodgkin's lymphoma - lymphocyte-rich type (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_morphologische_Merkmale-5\" >Clinical picture and morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik-10\" >Differential diagnosis and methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-33\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-32\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klassisches_lymphozytenarmes_Hodgkin-Lymphom_cHL\" >Classical lymphocyte-poor Hodgkin's lymphoma (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_morphologische_Merkmale-6\" >Clinical picture and morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnostik_und_-methodik-11\" >Differential diagnosis and methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostik-7\" >Diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-34\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-33\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Nodulares_lymphozytenpradominantes_Hodgkin-Lymphom_NLPHL-2\" >Nodular lymphocyte predominant Hodgkin lymphoma (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Klinisches_Bild_und_morphologische_Merkmale-7\" >Clinical picture and morphological features<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Differenzialdiagnosen_und_Differenzialmethodik\" >Differential diagnoses and differential methodology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Diagnostik-8\" >Diagnostics<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Therapie-35\" >Therapy<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Prognose-34\" >Forecast<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Standard-Therapeutika_Chemo\" >Standard therapeutics (chemo)<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Hodgkin-Lymphom-2\" >Hodgkin's lymphoma<\/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\/en\/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\/en\/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\/en\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Non-Hodgkin-Lymphom_NHL\" >Non-Hodgkin's lymphoma (NHL)<\/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\/en\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#R-Bendamustin\" >R-Bendamustine<\/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\/en\/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\/en\/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\/en\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Spezielle_Formen\" >Special shapes<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Standard-Therapeutika_%E2%80%93_Signalwege\" >Standard therapeutics - signaling pathways<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Bendamustin\" >Bendamustine<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Bleomycin\" >Bleomycin<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Cisplatin_Carboplatin\" >Cisplatin \/ carboplatin<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Cyclophosphamid\" >Cyclophosphamide<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Cytarabin_Ara-C\" >Cytarabine (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Dacarbacin\" >Dacarbacin<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Dexamethason\" >Dexamethasone<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Doxorubicin\" >Doxorubicin<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Etoposid\" >Etoposide<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Glukokortikoide_Prednison_Prednisolon\" >Glucocorticoids (prednisone \/ prednisolone)<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Ifosfamid\" >Ifosfamide<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Procarbazin\" >Procarbazine<\/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\/en\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Vincristin_Vinblastin\" >Vincristine \/ vinblastine<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Phyto-Therapiemoglichkeiten\" >Phyto-therapy options<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Huaier-Pilz_Trametes_robiniophila_Murr\" >Huaier's mushroom (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben\" >Sources<\/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\/en\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-2\" >Sources<\/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\/en\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-3\" >Sources<\/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\/en\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-4\" >Sources<\/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\/en\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-5\" >Sources<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Berberin_Berberis_vulgaris\" >Berberine (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-6\" >Sources<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Echinacea_Sonnenhut\" >Echinacea (coneflower)<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-7\" >Sources<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Kurkuma_Curcumin\" >Turmeric (curcumin)<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-8\" >Sources<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Ingwer_Gingerole\" >Ginger (gingerols)<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-9\" >Sources<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Zitrusfruchte_Quercetin\" >Citrus fruits &amp; quercetin<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-10\" >Sources<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Schwarzkummelol_Nigella_sativa\" >Black cumin seed oil (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-11\" >Sources<\/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\/en\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Quellenangaben-12\" >Sources<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Phyto-Therapeutika_%E2%80%93_Signalwege\" >Phyto-therapeutics - signaling pathways<\/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\/en\/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\/en\/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\/en\/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\/en\/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\/en\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Berberin_Berberis_vulgaris-2\" >Berberine (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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Echinacea_Sonnenhut-2\" >Echinacea (coneflower)<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Kurkuma_Curcumin-2\" >Turmeric (curcumin)<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Ingwer_Gingerole-2\" >Ginger (gingerols)<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Zitrusfruchte_Quercetin-2\" >Citrus fruits &amp; quercetin<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Schwarzkummelol_Nigella_sativa-2\" >Black cumin seed oil (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\/en\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Rituximab_%E2%80%93_die_Entwicklungsgeschichte\" >Rituximab - the history of development<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#1975_%E2%80%93_Entwicklung_der_Hybridoma-Technologie\" >1975 - Development of hybridoma technology<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Wie_konnen_Zellen_unsterblich_sein\" >How can cells be immortal?<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Plasmozytom_bei_Mausen_%E2%80%93_die_ursprungliche_Quelle\" >Plasmacytoma in mice - the original source<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Die_erste_gangige_Zelllinie_%E2%80%93_SP20\" >The first common cell line - 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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Warum_sind_Myelomzellen_unsterblich\" >Why are myeloma cells immortal?<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Normale_Zellen_%E2%80%93_Das_Hayflick-Limit\" >Normal cells - The Hayflick limit<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Krebszellen_sind_erfinderisch_%E2%80%93_aktivieren_Telomerase\" >Cancer cells are inventive - activate 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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Warum_Telomerase\" >Why 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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#TP53-Mutation_%E2%80%93_das_andere_Puzzle-Teil\" >TP53 mutation - the other piece of the 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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Wie_Myelomzellen_unsterblich_wurden\" >How myeloma cells became immortal<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Die_erste_SP20_Hybridoma-Zelle\" >The first SP2\/0 hybridoma cell<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Warum_keine_normale_B-Zellen\" >Why no normal B cells?<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Die_Fusion_%E2%80%93_der_Hybridoma-Prozess\" >The fusion - the hybridoma process<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Warum_Zellen_eines_Myeloms_und_nicht_anderer_Tumore\" >Why myeloma cells and not other tumors?<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Das_Paradoxe_%E2%80%93_Krebszellen_als_Mittel_gegen_Krebs\" >The paradox - cancer cells as a remedy for cancer<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Neuere_Alternativen\" >Newer alternatives<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Zusammenfassung-2\" >Summary<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#1980_%E2%80%93_Entdeckung_des_Oberflachenproteins_CD20\" >1980 - Discovery of the surface protein 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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Erstes_Experiment\" >First experiment<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Das_chimare_Antikorper-Problem\" >The chimeric antibody problem<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#1990-1992_%E2%80%93_Rituximab-Entwicklung\" >1990-1992 - Rituximab development<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Das_IDEC-Team\" >The IDEC team<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Entwicklung\" >Development<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#1993-1997_%E2%80%93_Klinische_Tests\" >1993-1997 - Clinical tests<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#1994_%E2%80%93_Phase-I-Studie\" >1994 - Phase I study<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#1997_%E2%80%93_Phase-II-Studie\" >1997 - Phase II study<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#1997_%E2%80%93_FDA-Zulassung_November\" >1997 - FDA approval (November)<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Warum_genau_dieser_Maus-Antikorper\" >Why exactly this mouse antibody?<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Seit_1997\" >Since 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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Dosierungsempfehlungen\" >Dosage recommendations<\/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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/#Fur_ABC-DLBCL\" >For ABC-DLBCL<\/a><\/li><\/ul><\/li><\/ul><\/nav><\/div>\n<span class=\"span-reading-time rt-reading-time\" style=\"display: block;\"><span class=\"rt-label rt-prefix\">Reading time<\/span> <span class=\"rt-time\"> 78<\/span> <span class=\"rt-label rt-postfix\">minutes<\/span><\/span>\n<p class=\"wp-block-paragraph\">There are dozens of types of lymphoma. Not every type responds to every therapy, and a therapy may even be counterproductive for a certain type of lymphoma.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">On the one hand, this overview is intended to support a solid diagnosis, and on the other hand, it is also intended to discuss specific - herbal - therapy options that are suitable depending on the type and subtype of lymphoma.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Where clinical studies on an adjuvant form of therapy exist, these are linked in the text. In vitro results are theoretically possible approaches or are based on laboratory tests that are not necessarily directly transferable to humans: What works in the Petri dish, in which the active substance comes into direct contact with a pathogen, may also cause different results due to different bioavailability in the organism.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">However, since medicine is generally not primarily interested in purely herbal active substances and their thorough research in the context of randomized, double-blind and peer-reviewed studies - dependent on appropriate funding - in the absence of possible patenting, the theoretical approach is an opportunity for interested physicians to offer their patients evidence-based herbal alternatives, which therefore - demonstrably - have their justification as adjuvants.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A differentiated presentation is given for each type of lymphoma, which includes the following aspects:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Clinical features<\/li>\n\n\n\n<li>Differential diagnostics<\/li>\n\n\n\n<li>Diagnostic methods<\/li>\n\n\n\n<li>(Standard) therapy and prognosis<\/li>\n\n\n\n<li>Alternative therapy option(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\">All the information provided here has been carefully researched to the best of our current knowledge, but is not a substitute for a consultation with a specialist.<\/p>\n<\/blockquote>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Wie_entstehen_Lymphom-Erkrankungen\"><\/span>How do lymphoma diseases develop?<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Lymphomas arise from a malignant transformation of lymphocytes<\/strong>, the white blood cells of the immune system. These cells, which normally fight infections, are altered by&nbsp;<strong>Stochastic processes in the genome<\/strong>, mostly through genetic changes such as chromosomal translocations or mutations. These changes cause the cells to&nbsp;<strong>uncontrolled proliferation<\/strong>, no longer die off and displace healthy tissue.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Although the exact cause of most lymphomas is not fully understood,&nbsp;<strong>certain factors play a role<\/strong>, which increase the risk of illness:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Sleeve<\/strong>The risk increases with age, especially from the age of 60.&nbsp;<\/li>\n\n\n\n<li><strong>Weakened immune system<\/strong>Lymphomas occur more frequently in people with immunosuppression (e.g., after organ transplantation, HIV, or autoimmune diseases).&nbsp;<\/li>\n\n\n\n<li><strong>Infections<\/strong>Some viruses (like Epstein-Barr virus) or bacteria (like&nbsp;<em>Helicobacter pylori<\/em>) can favor certain types of lymphoma.&nbsp;<\/li>\n\n\n\n<li><strong>Environmental factors<\/strong>Radiation (e.g., X-rays, radioactivity) and chemical pollutants (e.g., pesticides, benzene) can promote its development.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Einleitung\"><\/span>Introduction<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Lymphoma diseases are <strong>non-heritable<\/strong>, <strong>non-contagious<\/strong>, <strong>rarely<\/strong>, \u2013 however, good prognoses for an uncomplicated recovery are even rarer.<br>Even if the prognosis is initially very positive, successful radiation therapies cause damage that may only appear years or a decade later.<br>Even expedient and therapeutically sensible stem cell transplants (like organ transplants) can cause lymphomas in immunosuppressed patients in the first few years, or in a second attempt after about 5-10 years.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Even though chemotherapeutic agents attack target cells more or less \u201eselectively,\u201c they must also act systemically, meaning throughout the entire organism, due to systemic infestation. Therefore, the known side effects of chemotherapy are always relevant to the patient in their impact.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Therefore, everything must be done that is suitable to strengthen the organism with regard to the necessarily systemically damaging effects of chemotherapy and radiation therapy.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This can be done by a suitable <strong>Dietary change<\/strong>but also <a href=\"#PTM\">Use of adjuvant herbal active ingredients<\/a> occur, which have an immune-boosting and immune-regulating effect.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A <strong>strong (!) immune system<\/strong> can't be easily intimidated and <strong>resists<\/strong> den \u2014 unwanted \u2014 manipulations of chemo- and radiotherapy measures <strong>significantly better<\/strong>.<br>And yes, the <strong>With an area of around 260-300 m, the intestine represents<sup>2<\/sup> around 70-80 % of the human immune system<\/strong>:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The majority of these immune cells are located in the intestinal mucosa and form the&nbsp;<strong>gut-associated lymphoid tissue (GALT)<\/strong>.&nbsp;<br>This is where immune cells are educated, trained and activated to distinguish between harmless substances (such as food and intestinal bacteria) and dangerous intruders (such as bacteria or viruses). <\/p>\n\n\n\n<p class=\"wp-block-paragraph\">However, the worst strategy in every respect is the ostrich policy! <strong>It is definitely essential to adhere precisely to examination intervals.<\/strong>, because lymphomas can change (transform) and, with omitted, late (follow-up) diagnostics or as a result of incorrect therapy, this usually leads to a significant disadvantage for the patient.<br>Those who act vigilantly and proactively are clearly at an advantage!<\/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>Overview of lymphoma types<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Lymphomas are classified according to <strong>WHO classification<\/strong> (2022) are divided into two main groups with various subspecies:<\/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>Hodgkin's lymphoma (approx. 10-15% of all lymphomas)<\/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>Classical Hodgkin's lymphoma (cHL)<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"#cHL_NS\">Nodular sclerosis (NS)<\/a> (60-70%) - most common form<\/li>\n\n\n\n<li><a href=\"#cHL_MC\">Chimerism (MC) <\/a>(15-20%)<\/li>\n\n\n\n<li><strong><a href=\"#cHL_LR\">Lymphocyte-rich (LR)<\/a><\/strong> (5%)<\/li>\n\n\n\n<li><a href=\"#cHL\"><strong>Lymphocyte-poor<\/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\">Nodular lymphocyte-dominant HL (NLPHL)<\/a><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Rarer variant with better prognosis<\/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>Non-<strong>Hodgkin's lymphoma<\/strong><\/strong>e<strong> (NHL, approx. 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>B-cell lymphomas (80% of all NHL)<\/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>Indolent (low-malignant) B-cell lymphomas:<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"#FL\"><strong>Follicular lymphoma<\/strong> (FL) <\/a>- Most common indolent form<\/li>\n\n\n\n<li><strong><a href=\"#LPL\">Lymphoplasmocytic lymphoma<\/a><\/strong> \/ Waldenstr\u00f6m's macroglobulinemia<\/li>\n\n\n\n<li><a href=\"#CLL_SLL\"><strong>Small lymphocytic leukemia\/lymphoma<\/strong> (SLL\/CLL)<\/a><\/li>\n\n\n\n<li><a href=\"#NMZL\"><strong>Nodal marginal zone lymphoma<\/strong> (NMZL)<\/a><\/li>\n\n\n\n<li><a href=\"#SMZL\"><strong>Splenic marginal zone lymphoma<\/strong> (SMZL)<\/a><\/li>\n\n\n\n<li><a href=\"#CL\"><strong>Primary cutaneous lymphoma<\/strong> (Mycosis fungoides\/S\u00e9zary syndrome)<\/a><\/li>\n\n\n\n<li><a href=\"#PDBZLM\"><strong>Primary duodenal B-cell lymphoma<\/strong> (MALT type)<\/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>Aggressive B-cell lymphomas:<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"#DLBCL\"><strong>Diffuse large B-cell lymphoma<\/strong> (DLBCL)<\/a> - Most common aggressive form<br>\u2013 NOS (Not Otherwise Specified)<br>- <a href=\"#pMBCL\">Primary mediastinal DLBCL (pMBCL)<\/a><br>\u2014 Highly transformed lymphoma<\/li>\n\n\n\n<li><strong><a href=\"#BL\">Burkitt's lymphoma<\/a><\/strong> - very aggressive, fast growth<\/li>\n\n\n\n<li><strong><a href=\"#LBL\">Lymphoblastic lymphoma<\/a><\/strong><\/li>\n\n\n\n<li><a href=\"#PKDGBZL\"><strong>Primary cutaneous large cell lymphoma<\/strong> (centrotaximal variant)<\/a><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"GrauzonenGrenzfalle\"><\/span><strong>Gray areas\/borderline cases:<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong><a href=\"#BLu\">B-cell lymphoma, unclassifiable<\/a><\/strong> (between DLBCL and Burkitt)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Spezielle_extranoduale_Lymphome\"><\/span><strong>Special extranodal lymphomas:<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"#HSTL\"><strong>Hepatosplenic lymphoma<\/strong> (HSTL)<\/a><\/li>\n\n\n\n<li><strong><a href=\"#IVGBL\">Intravascular large B-cell lymphoma<\/a><\/strong><\/li>\n\n\n\n<li><a href=\"#PEL\"><strong>Primary efflusion lymphoma<\/strong> (PEL)<\/a><\/li>\n\n\n\n<li><strong><a href=\"#PEL\">HHV8-associated lymphomas<\/a><\/strong><\/li>\n\n\n\n<li><strong><a href=\"#EMZL_MALT\">MALT lymphoma<\/a><\/strong> (stomach, intestines, other organs)<\/li>\n\n\n\n<li><strong><a href=\"#EMZL_MALT\">Nodal\/extranodal marginal zone lymphoma<\/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>T-cell and NK-cell lymphomas (20% of all NHL)<\/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>Peripheral T-cell lymphomas (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\">Peripheral T-cell lymphoma, NOS<\/a><\/strong> - most common T-cell form<\/li>\n\n\n\n<li><a href=\"#AITL\" data-type=\"internal\" data-id=\"#AITL\"><strong>Angioimmunoblastic T-cell lymphoma<\/strong> (AITL)<\/a><\/li>\n\n\n\n<li><a href=\"#PTFCL\"><strong>Follicular helper T-cell lymphoma<\/strong> (PTFCL)<\/a><\/li>\n\n\n\n<li><a href=\"#HTZL\"><strong>Hepatosplenic T-cell lymphoma<\/strong> (\u03b3\u03b4-type)<\/a><\/li>\n\n\n\n<li><strong><a href=\"#EATZL\">Enteropathy-associated T-cell lymphoma<\/a><\/strong><\/li>\n\n\n\n<li><a href=\"#ALCL\"><strong>Anaplastic large cell lymphoma<\/strong> (ALCL)<\/a><br>\u2013 ALK-positive (better prognosis)<br>\u2013 ALK-negative<br>\u2013 Primary cutaneous variant<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Kutane_T-Zell-Lymphome\"><\/span><strong>Cutaneous T-cell lymphomas:<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong><a href=\"#KTMF\">Mycosis fungoides<\/a><\/strong> (most common cutaneous T-cell form)<\/li>\n\n\n\n<li><strong><a href=\"#SSMF\">S\u00e9zary syndrome<\/a><\/strong> (blood involvement of MF)<\/li>\n\n\n\n<li><strong><a href=\"#PKAGL\">Primary cutaneous anaplastic large cell lymphoma<\/a><\/strong><\/li>\n\n\n\n<li><strong><a href=\"#KML\">Cutaneous marginal zone lymphoma<\/a><\/strong><\/li>\n\n\n\n<li><strong><a href=\"#KLKM\">Cutaneous lymphoma with granular middle finger tattoo<\/a><\/strong><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Lymphoblastische_Lymphome\"><\/span><strong>Lymphoblastic lymphomas:<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong><a href=\"#BALL\">B-lymphoblastic lymphoma\/leukemia (B-ALL)<\/a><\/strong><br>more often <\/li>\n\n\n\n<li><strong><a href=\"#TALL\">T-lymphoblastic lymphoma\/leukemia (T-ALL)<\/a><\/strong><br>rarer (and T-cell lymphoma)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Note: If &gt;25% blasts in the BM (bone marrow) or blood, then rather <strong>Leukemia<\/strong>-Diagnosis<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"NK-Zell-Lymphome\"><\/span><strong>NK cell lymphomas:<\/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\">Extranodal NK cell lymphoma<\/a><\/strong> (associated with EBV)<\/li>\n\n\n\n<li><a href=\"#ANKL\"><strong>Aggressive NK-cell leukemia<\/strong> (ANKL)<\/a><\/li>\n\n\n\n<li><strong><a href=\"#CNKL\">Chronic NK cell leukemia<\/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>Hodgkin's lymphoma<\/strong> - Related diseases<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"#NLDHL\">Nodular lymphocyte-dominant HL<\/a><\/li>\n\n\n\n<li><a href=\"#PTLD\">EBV-positive large B-cell lymphoma (post-transplant lymphoproliferative disorder)<\/a><\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Immunproliferative_Erkrankungen_Grenzfalle\"><\/span><strong>Immunoproliferative diseases &amp; borderline cases<\/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\">MALT lymphomas<\/a><\/strong> (Mucosa-Associated Lymphoid Tissue)<\/li>\n\n\n\n<li><strong><a href=\"#IEG_LG\">Lymphomatoid granulomatosis<\/a><\/strong><\/li>\n\n\n\n<li><strong><a href=\"#GANZ\">Granulomatosis with organ-preserving vasculitis (GANZL)<\/a><\/strong><\/li>\n\n\n\n<li><strong><a href=\"#IEG_EBVBL\">EBV-associated B-cell lymphoproliferations<\/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>Epidemiological overview<\/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>Lymphoma type<\/th><th>Frequency<\/th><th>Median age<\/th><th>5-Y. Survival<\/th><\/tr><\/thead><tbody><tr><td><strong>Total non-Hodgkin's lymphomas (NHL)<\/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 Hodgkin's lymphoma (HL)<\/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>Most important NHL subtypes:<\/strong><\/td><td><\/td><td><\/td><td><\/td><\/tr><tr><td>Follicular lymphoma (FL)<\/td><td>20% (from NHL)<\/td><td>65 J.<\/td><td>85-90%<\/td><\/tr><tr><td>DLBCL<\/td><td>35% (from NHL)<\/td><td>70 J.<\/td><td>65-75%<\/td><\/tr><tr><td>Small lymphocytic leukemia\/lymphoma (CLL\/SLL)<\/td><td>15% (from NHL)<\/td><td>70 J.<\/td><td>75%+<\/td><\/tr><tr><td>Burkitt's lymphoma<\/td><td>2-3% (from NHL)<\/td><td>50 J.<\/td><td>80-90%<\/td><\/tr><tr><td>Angioimmunoblastic T-cell lymphoma (AITL)<\/td><td>2-3% (from NHL)<\/td><td>75 J.<\/td><td>32%<\/td><\/tr><tr><td>MALT lymphoma<\/td><td>5-10% (from 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>Classification according to biology (prognosis)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Indolent<\/strong> (slow growth, poorer chances of recovery, but long survival times)<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Follicular lymphoma, CLL\/SLL, MALT<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Aggressive<\/strong> (rapid growth, better chances of recovery with modern chemotherapy)<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>DLBCL, Burkitt's lymphoma, Hodgkin's lymphoma<\/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>Differential Representation \u2013 <strong>Non-Hodgkin lymphoma<\/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>Follicular lymphoma (FL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The current WHO classification (WHO-HAEM-5) divides follicular lymphomas into:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Classic type (cFL)<\/strong><br>Corresponds to former grades 1, 2, 3A (indolent)<\/li>\n\n\n\n<li><strong>Follicular large B-cell lymphoma (FLBL)<\/strong><br>Corresponds to former grade 3B (aggressive)<\/li>\n\n\n\n<li><strong>FL with unusual characteristics (uFL)<\/strong><br>new provisional entity<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Genetic subtypes: 90% have t(14;18)* with BCL2 rearrangement; less frequently t(8;14) with MYC translocation (poor prognosis); 70% major breakpoint region (MBR)**, 10-15% minor breakpoint region (mbr)***.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">* t(14;18) - indicates (in simplified form) a translocation between chromosome 8 and chromosome 14. Written out in full, it would read t(8;14)(q24;q32), the translocation supplemented by the band positions, which are <strong>Precise cytogenetic localization<\/strong> q, which breaks the band&nbsp;<strong>q24<\/strong>&nbsp;of chromosome 8 (MYC gene) and band&nbsp;<strong>q32<\/strong>&nbsp;of chromosome 14 (IGH locus).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">** The MBR is located in the&nbsp;<strong>Switch-\u03bc range (S\u03bc)<\/strong>&nbsp;of the IGH locus, just upstream of the constant region gene C\u03bc. This region is a target of the&nbsp;<strong>class-specific recombination (Class Switch Recombination, CSR)<\/strong>&nbsp;in B cells, which indicates a misdirected physiological process as the cause of the translocation.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">*** The mbr is also in the S\u03bc range, but somewhat&nbsp;<strong>upstream (5\u2032) to the MBR<\/strong> and with <strong>approx. 10-15 %<\/strong>&nbsp;is involved in the t(8;14) translocation. This region is also attacked during CSR, but less frequently than the MBR.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In both cases (MBR and mbr), the translocation results in the&nbsp;<strong>MYC gene (8q24)<\/strong>&nbsp;under the control of the strong enhancers of the&nbsp;<strong>IGH-Lokus<\/strong>&nbsp;which leads to a&nbsp;<strong>constitutive overexpression of MYC<\/strong>&nbsp;and thus leads to uncontrolled cell proliferation.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The remaining cases have breakpoints in other switch regions (e.g. S\u03b1, S\u03b3) or in the JH region, which also results in the&nbsp;<strong>MYC gene (8q24)<\/strong>&nbsp;comes under the control of strong regulatory elements of the IGH locus, which&nbsp;<strong>constitutive overexpression of MYC<\/strong>&nbsp;and thus causes tumor development.<\/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>Lymphoplasmocytic lymphoma - Waldenstr\u00f6m's macroglobulinemia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>Lymphoplasmocytic lymphoma (LPL)<\/strong>also&nbsp;<strong>Waldenstr\u00f6m's disease-macroglobulinemia (WM)<\/strong>&nbsp;is a rare, chronic lymphoproliferative disease that belongs to the group of mature B-cell neoplasms.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It is characterized by a&nbsp;<strong>Lymphoplasmocytic infiltration of the bone marrow<\/strong>, the production of a&nbsp;<strong>monoclonal IgM antibody (paraprotein)<\/strong>&nbsp;and a mostly indolent, slowly progressing form.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The disease occurs predominantly in older adults (mean age of diagnosis: 65-72 years), with men being affected twice as often as women.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisch-morphologische_Merkmale\"><\/span><strong>Clinical-morphological features<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Histological<\/strong>&nbsp;the lymphoma shows a dense, diffuse or follicular infiltrate of small lymphocytes, plasmacytoid lymphocytes and plasma cells in the bone marrow and other organs<\/li>\n\n\n\n<li>The tumor cells are&nbsp;<strong>CD19+, CD20+, CD22+ (weak)<\/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;and&nbsp;<strong>IgM+<\/strong><\/li>\n\n\n\n<li><strong>BCL2<\/strong>&nbsp;is expressed in approx. 98 % cases and represents a therapeutic target<\/li>\n\n\n\n<li>The&nbsp;<strong>Increase in the IgM level<\/strong>&nbsp;leads to increased blood viscosity, which can result in symptoms such as headaches, dizziness, impaired vision and hearing, nosebleeds and Raynaud's phenomenon<\/li>\n\n\n\n<li><strong>Characteristic symptoms<\/strong>&nbsp;include: B-symptoms (fever, night sweats, weight loss), anemia (pallor, weakness), thrombocytopenia (bleeding tendency), polyneuropathy (tingling, pain in extremities) and cryoglobulinemia\/cold agglutinin disease with cold dependence of IgM aggregation<\/li>\n\n\n\n<li><strong>Complications<\/strong> can be light chain amyloidosis (organ damage), organ infiltration (spleen, liver enlargement), infections due to immunosuppression<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik\"><\/span><strong>Differential diagnosis<\/strong>tic<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The differential diagnosis includes other diseases with monoclonal IgM production or lymphoplasmocytic infiltration:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>IgM monoclonal gammopathy of unknown significance (IgM-MGUS)<\/strong><br>IgM &lt; 30 g\/l, &lt; 10 % plasma cells in the bone marrow, no symptoms<br>Progression rate: 1.5-2 % per year<\/li>\n\n\n\n<li><strong>Other non-Hodgkin's lymphomas<\/strong>:<br>- <strong>Marginal zone lymphoma (MZL)<\/strong><br>Can be IgM- or IgG-secreting, but usually without bone marrow involvement<br>- <strong>Chronic lymphocytic leukemia (B-CLL)<\/strong><br>CD5+, CD23+, CD20+, IgM-positive, but mostly without IgM paraprotein<br>- <strong>Diffuse large B-cell lymphoma (DLBCL)<\/strong><br>Aggressive course, different immunophenotype<\/li>\n\n\n\n<li><strong>Multiple myeloma (plasmacytoma)<\/strong><br>Osteolytic lesions, hypercalcemia, only rarely IgM secretion<\/li>\n\n\n\n<li><strong>Hepatitis, HIV, rheumatoid arthritis<\/strong><br>can secondarily increase IgM<\/li>\n\n\n\n<li><strong>Other IgM-LPL without bone marrow involvement<\/strong>&nbsp;(non-Morbus Waldenstr\u00f6m LPL): e.g. IgG\/IgA LPL, non-secretory LPL (WHO 2022)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methoden\"><\/span><strong>Diagnostic methods<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Diagnosis is based on a combination of clinical, laboratory and molecular genetic tests:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Serum and urine electrophoresis<\/strong>&nbsp;+&nbsp;<strong>Immunofixation<\/strong><br>Detection of a monoclonal IgM protein<\/li>\n\n\n\n<li><strong>Bone marrow biopsy<\/strong><br>Confirmation of lymphoplasmocytic infiltration (&gt;10 % clonal cells)<\/li>\n\n\n\n<li><strong>Cytomorphology<\/strong><br>Assessment of the blood and bone marrow smear<\/li>\n\n\n\n<li><strong>Immunophenotyping (flow cytometry)<\/strong><br>CD19+, CD20+, CD22+, CD27+, CD38+, CD52+, IgM+, CD5-, CD23-<\/li>\n\n\n\n<li><strong>Chromosome analysis<\/strong><br>Deletion of the long arm of chromosome 6 (del(6q)) at ~50 %, gain of 6p, gains of chromosomes 4, 8, 3, 18, deletions in the long arm of chromosome 13<\/li>\n\n\n\n<li><strong>FISH (fluorescence in situ hybridization)<\/strong>Detection of del(6q), del(11q) (ATM), del(17p) (TP53) - the latter with unfavorable progression<\/li>\n\n\n\n<li><strong>Molecular genetics (NGS)<\/strong><br>- <strong>MYD88 L265P mutation<\/strong>With&nbsp;<strong>~90-95 %<\/strong>&nbsp;of the WM patients -&nbsp;<strong>diagnostically highly specific<\/strong><br>- <strong>CXCR4-S338X (WHIM variant)<\/strong><br>With&nbsp;<strong>~30 %<\/strong>&nbsp;- associated with poorer response to ibrutinib, more aggressive course<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie\"><\/span><strong>Therapy<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The therapy depends on symptoms, risk, age, general condition and genotype:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Asymptomatic WM<\/strong> (Waldenstr\u00f6m's macroglobulinemia)<br><strong>Observation<\/strong>&nbsp;(\u201ewatch and wait\u201c), life expectancy comparable to age group<\/li>\n\n\n\n<li><strong>Symptomatic W<\/strong>M - <strong>First-line therapy<\/strong><br><strong>Chemoimmunotherapy (CIT)<\/strong><br>- <strong>DRC (dexamethasone-rituximab-cyclophosphamide)<\/strong>: For elderly or frail patients<br>- <strong>BR (Bendamustine-Rituximab)<\/strong>: For fit patients, rapid disease control<br><strong>BTK inhibitors (BTKi)<\/strong><br>- <strong>Ibrutinib<\/strong>,&nbsp;<strong>Zanubrutinib<\/strong>:&nbsp;<strong>First-line indication<\/strong>, especially in patients with&nbsp;<strong>MYD88 L265P<\/strong><br><strong>Not suitable for MYD88 WT \/ CXCR4 WT<\/strong><br>- High response rates (&gt;80 %), good tolerability, continuous therapy<\/li>\n\n\n\n<li><strong>Bortezomib-based therapies<\/strong><br>(e.g. bortezomib-rituximab) - Rapid control, for patients with high disease burden<\/li>\n\n\n\n<li><strong>Stem cell transplantation<\/strong><br>In young, agile patients with recurrent disease (rare)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose\"><\/span><strong>Forecast<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Median overall survival<\/strong><br>&gt;10 years (in asymptomatic patients even close to the normal population)<\/li>\n\n\n\n<li><strong>Prognostic factors<\/strong><br><strong>Inexpensive<\/strong>MYD88 L265P mutation, 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>Small lymphocytic leukemia \/ lymphoma (CLL\/SLL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">This is a <strong>homogeneous entity<\/strong> (not a subtype in the classical sense), but with prognostic subcategories:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Mutated IGHV<\/strong> (~50%)<br>Better prognosis<\/li>\n\n\n\n<li><strong>Unmutated IGHV<\/strong> (~50%)<br>Poorer prognosis<\/li>\n\n\n\n<li><strong>Del(13q)<\/strong><br>favorable risk factor<\/li>\n\n\n\n<li><strong>Del(11q)<\/strong> \/ <strong>TP53 mutation<\/strong><br>unfavorable risk factors<\/li>\n\n\n\n<li><strong>Del(17p)<\/strong> \/ <strong>TP53 mutation<\/strong><br>Very unfavorable prognosis<\/li>\n\n\n\n<li><strong>Complex Karyotype<\/strong> (\u22653 aberrations)<br>worse<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>Chronic lymphocytic leukemia (CLL)<\/strong>&nbsp;and that&nbsp;<strong>small cell B-cell lymphoma (SLL)<\/strong>&nbsp;are considered a common entity of indolent B-cell lymphomas according to the WHO 2022 classification.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Both diseases have an identical immunophenotypic and histologic profile, but differ clinically in the site of involvement: In the&nbsp;<strong>CLL<\/strong>&nbsp;dominates the&nbsp;<strong>leukemic infiltration of the peripheral blood and bone marrow<\/strong>, while the&nbsp;<strong>SLL<\/strong>&nbsp;the&nbsp;<strong>Extramedullary involvement of lymph nodes, spleen or other organs<\/strong>&nbsp;is in the foreground (blood lymphocytes &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>Clinical features<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Frequency<\/strong><br>CLL is the most common leukemic disease in Germany with a new case rate of approx. 5,600\/year<\/li>\n\n\n\n<li><strong>Median age of onset<\/strong><br>72 years (men), 76 years (women)<\/li>\n\n\n\n<li><strong>Symptoms<\/strong><br>Many patients are asymptomatic at the time of diagnosis. With advanced disease&nbsp;<strong>B symptoms<\/strong>&nbsp;(fever, night sweats, weight loss),&nbsp;<strong>Lymphadenopathy<\/strong>,&nbsp;<strong>Hepato- and splenomegaly<\/strong>,&nbsp;<strong>Cytopenias<\/strong>&nbsp;(anemia, thrombocytopenia) or&nbsp;<strong>Autoimmune cytopenias<\/strong>&nbsp;on<\/li>\n\n\n\n<li><strong>Blood smear<\/strong><br>Dominance of small, mature lymphocytes with&nbsp;<strong>dense, cloddy chromatin<\/strong>,&nbsp;<strong>narrow cytoplasmic rim<\/strong>&nbsp;and&nbsp;<strong>Gumprecht's core shadow<\/strong>&nbsp;(typical, but not pathognomonic)<\/li>\n\n\n\n<li><strong>Bone marrow<\/strong><br>Infiltration by small lymphocytes, often with loss of the germinal centers<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-2\"><\/span>Differential diagnostics<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>Diagnostic criteria (according to IWCLL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Permanent lymphocytosis (&gt; 3 months) with \u2265 5 \u00d7 10\u2079\/L monoclonal B cells in the peripheral blood<\/li>\n\n\n\n<li>Morphologically: predominance of small, mature lymphocytes in the blood smear<\/li>\n\n\n\n<li>Immunophenotype:&nbsp;<strong>CD5+, CD19+, CD23+<\/strong>,&nbsp;<strong>CD20(dim), CD79b(dim)<\/strong>,&nbsp;<strong>CD200+, ROR1+<\/strong>;&nbsp;<strong>weak\/sIg<\/strong>,&nbsp;<strong>no CD10<\/strong>,&nbsp;<strong>none FMC7<\/strong><\/li>\n\n\n\n<li><strong>Monoclonality<\/strong>Detection of light chain restriction (kappa or lambda) using CD19\/Ig\u03ba or CD19\/Ig\u03b3<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnosen\"><\/span><strong>Differential diagnoses<\/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\">Disease<\/td><td class=\"has-text-align-left\" data-align=\"left\">Criteria for differentiation<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Monoclonal B-cell lymphocytosis (MBL)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">&lt; 5 \u00d7 10\u2079\/L monoclonal B cells,&nbsp;<strong>No symptoms<\/strong>,&nbsp;<strong>No lymph node enlargement<\/strong>,&nbsp;<strong>no cytopenias<\/strong><\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Mantle cell lymphoma (MCL)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>t(11;14)(q13;q32)<\/strong>,&nbsp;<strong>CD5+<\/strong>, but&nbsp;<strong>CD23-<\/strong>,&nbsp;<strong>cyclin D1+<\/strong>,&nbsp;<strong>CD5+ prolymphocytes &gt; 15%<\/strong>&nbsp;(for prolymphocytic progression)<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>B-cell prolymphocytic leukemia (B-PLL)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>&gt; 55% Prolymphocytes<\/strong>&nbsp;in the blood,&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>Hairy cell leukemia (HCL)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>\u201eHair cells\u201c<\/strong>&nbsp;with an irregular cytoplasmic structure,&nbsp;<strong>CD103+, CD123+, CD25+<\/strong>,&nbsp;<strong>TRAP+<\/strong>,&nbsp;<strong>reticular fibrosis in the bone marrow<\/strong><\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Richter transformation (CLL \u2192 DLBCL)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Extramedullary lymphoma progression<\/strong>&nbsp;(2-5% of cases),&nbsp;<strong>Aggressive course<\/strong>,&nbsp;<strong>DLBCL type<\/strong>&nbsp;(centroblastic\/immunoblastic),&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>Diagnostic methods<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cytomorphology<\/strong><br>EDTA blood, obligatory<\/li>\n\n\n\n<li><strong>Immunophenotyping<\/strong><br>EDTA or heparin<br><strong>Matutes score<\/strong>&nbsp;Classification<\/li>\n\n\n\n<li><strong>FISH<\/strong><br>Standard panel<br><strong>del(13q), del(11q), +12, del(17p)<\/strong>,&nbsp;<strong>IGH rearrangements<\/strong>&nbsp;(e.g. t(11;14), t(14;18))<\/li>\n\n\n\n<li><strong>Chromosome analysis<\/strong><br><strong>Heparin<\/strong>-blood;&nbsp;<strong>Complex karyotype (\u22653 aberrations)<\/strong>&nbsp;is prognostically unfavorable<\/li>\n\n\n\n<li><strong>Molecular genetics<\/strong><br><strong>IGHV mutation status<\/strong>&nbsp;(unmutated = unfavorable),&nbsp;<strong>TP53, ATM, NOTCH1, SF3B1<\/strong>-mutations<\/li>\n\n\n\n<li><strong>MRD detection<\/strong><br>Sensitivity \u2265 10-\u2074; important for therapy monitoring<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-2\"><\/span><strong>Forecast<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The prognosis is highly heterogeneous and is determined by several factors:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>IGHV mutation status<\/strong>:&nbsp;<strong>Unmutated (U-CLL)<\/strong>&nbsp;= unfavorable<\/li>\n\n\n\n<li><strong>Hypermutated (H-CLL)<\/strong>&nbsp;= favorable<\/li>\n\n\n\n<li><strong>Chromosomal aberrations (FISH)<\/strong>:<br>- <strong>del(17p)<\/strong>:&nbsp;<strong>Unfavorable<\/strong>,&nbsp;<strong>TP53 change<\/strong>&nbsp;\u2192 Resistance to therapy.<br>- <strong>del(11q)<\/strong>Unfavorable, often with lymphadenopathy.<\/li>\n\n\n\n<li><strong>Complex karyotype<\/strong><br>Independent prognostic factor (unfavorable).&nbsp;<\/li>\n\n\n\n<li><strong>Molecular genetics<\/strong><br><strong>NOTCH1, SF3B1, BIRC3<\/strong>-mutations \u2192 unfavorable, especially in recurrence<\/li>\n\n\n\n<li><strong>CLL-IPI (International Prognostic Index)<\/strong><br>Takes into account age, Binet stage, \u03b2\u2082 microglobulin, IGHV, del(17p), TP53 mutation<br>Valuable for&nbsp;<strong>PFS<\/strong> (progression-free survival), less for&nbsp;<strong>O.S<\/strong> (overall survival) under targeted therapy<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-2\"><\/span><strong>Therapy<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The therapy depends on the&nbsp;<strong>Need for treatment<\/strong>,&nbsp;<strong>Prognostic factors<\/strong>&nbsp;and&nbsp;<strong>Patient profile<\/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>Indication for therapy (according to iwCLL\/Onkopedia)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Symptoms<\/strong>B-symptoms, cytopenias, progression of lymphadenopathy<\/li>\n\n\n\n<li><strong>Laboratory criteria<\/strong>:&nbsp;<strong>Lymphocytes &gt; 30 \u00d7 10\u2079\/L<\/strong>,&nbsp;<strong>Cell doubling time &lt; 12 months<\/strong>,&nbsp;<strong>progressive cytopenias<\/strong><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Behandlungsoptionen\"><\/span><strong>Treatment options<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Targeted therapies (primary therapy)<\/strong><br>- <strong>Ibrutinib (BTK inhibitor)<\/strong><br><strong>Standard for TP53 alterations or unmutated IGHV<\/strong><br>- <strong>Venetoclax (BCL-2 inhibitor)<\/strong><br>Combination with&nbsp;<strong>Obinutuzumab<\/strong><br>especially with&nbsp;<strong>del(17p)<\/strong>&nbsp;or&nbsp;<strong>TP53 mutation<\/strong><\/li>\n\n\n\n<li><strong>Combination therapy (for fitter patients)<\/strong><br>- <strong>Obinutuzumab + chlorambucil<\/strong>&nbsp;or&nbsp;<strong>FCR (fludarabine, cyclophosphamide, rituximab)<\/strong><br>only for&nbsp;<strong>favorable risk (hypermutated, no TP53 alteration)<\/strong><\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Marginalzonen-Lymphome\"><\/span><strong>Marginal zone lymphomas<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Marginal zone lymphoma (MZL)<\/strong>&nbsp;are a group of indolent B-cell lymphomas that can be divided into three main subtypes according to their primary localization:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>extranodal MZL (MALT lymphoma)<\/strong><\/li>\n\n\n\n<li><strong>nodal MZL (nMZL)<\/strong><\/li>\n\n\n\n<li><strong>Splenic MZL (SMZL)<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">All three subtypes originate from mature B-cell tissue, but show different clinical, genetic and therapeutic characteristics.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Extranodales_Marginalzonen-Lymphom_MALT-Lymphom\"><\/span><strong>Extranodal marginal zone lymphoma (MALT lymphoma)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Origin<\/strong><br>Primarily in non-lymphatic organs (e.g. stomach, salivary glands, eye, skin, lungs)<\/li>\n\n\n\n<li><strong>Frequency<\/strong><br>approx. 8% of all lymphomas, with stomach as the most frequent localization (30-35%)<\/li>\n\n\n\n<li><strong>Pathogenesis<\/strong><br>Frequently associated with chronic antigen stimulation by&nbsp;<strong>Helicobacter pylori<\/strong>-Infection (stomach) <br>or autoimmune diseases (e.g. Sj\u00f6gren's syndrome, Hashimoto's thyroiditis)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-3\"><\/span><strong>Differential diagnostics<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>To be distinguished from&nbsp;<strong>diffuse large B-cell lymphoma (DLBCL)<\/strong>,&nbsp;<strong>follicular lymphoma<\/strong>&nbsp;and&nbsp;<strong>chronic lymphocytic leukemia (CLL)<\/strong><\/li>\n\n\n\n<li>Classic&nbsp;<strong>lymphoepithelial lesions<\/strong>&nbsp;with invasion of the epithelium by clonal B cells are characteristic<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnosemethodik\"><\/span><strong>Diagnostic methodology<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Histological examination of the affected organ (e.g. stomach biopsy)<\/li>\n\n\n\n<li><strong>Gastroscopy<\/strong>,&nbsp;<strong>Colonoscopy<\/strong>,&nbsp;<strong>Ultrasound<\/strong>,&nbsp;<strong>PET-CT<\/strong>&nbsp;(for staging)<\/li>\n\n\n\n<li>Immunohistochemistry:&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>Therapy and prognosis<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>First line<\/strong>:&nbsp;<strong>Antibiotic eradication of H. pylori<\/strong>&nbsp;(remission rates up to 80%)<\/li>\n\n\n\n<li>In case of non-response or extragastric MALT lymphoma:&nbsp;<strong>Radiotherapy<\/strong>&nbsp;(24 Gy) or&nbsp;<strong>System therapy<\/strong>&nbsp;(e.g.&nbsp;&nbsp;<strong>Rituximab + bendamustine<\/strong>,&nbsp;<strong>Rituximab + chlorambucil<\/strong>)<\/li>\n\n\n\n<li><strong>Zanubrutinib<\/strong>&nbsp;(BTK inhibitor) as a new approach for recurrence or refractory disease<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Nodales_Marginalzonen-Lymphom_nMZL\"><\/span><strong>Nodal marginal zone lymphoma (nMZL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The <strong>Nodal marginal zone lymphoma<\/strong> is a rare, indolent B-cell lymphoma, accounting for approximately 0.5-1% of all lymphomas and 10% of all MZL.&nbsp;<strong>Lymph nodes<\/strong>, without extranodal or splenic infestation.<br>It belongs to the group of marginal zone lymphomas (MZL), which also includes extranodal (MALT lymphoma) and splenic marginal zone lymphoma.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_Merkmale-2\"><\/span>Clinical features<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Similar to the&nbsp;<strong>follicular lymphoma<\/strong><br>Advanced stage at diagnosis, lymph node enlargement, bone marrow involvement (approx. 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>Differentiation between splenic and extranodal MZL<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>nMZL<\/strong><br>The primary infestation affects&nbsp;<strong>only the lymph nodes<\/strong><br>It lies&nbsp;<strong>No infestation of the spleen (splenic)<\/strong>&nbsp;and&nbsp;<strong>No extranodal infestation<\/strong>&nbsp;(e.g. stomach, salivary gland, eye) before<\/li>\n\n\n\n<li><strong>Splenic MZL<\/strong><br>Infestation of the&nbsp;<strong>Spleen<\/strong>, often with&nbsp;<strong>Bone marrow infiltration<\/strong>&nbsp;and&nbsp;<strong>leukemic involvement<\/strong>&nbsp;of the peripheral blood<\/li>\n\n\n\n<li><strong>Extranodal MZL (MALT lymphoma)<\/strong><br>Starts in&nbsp;<strong>non-lymphatic organs<\/strong>&nbsp;(e.g. stomach, salivary gland, eye) and often shows an association with chronic inflammation (e.g.&nbsp;<em>Helicobacter pylori<\/em>, Sj\u00f6gren's syndrome)<\/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>Differentiation from other indolent B-cell lymphomas<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Follicular lymphoma (FL)<\/strong><br>Similar clinical picture and treatment approach, but histologically different cell structure (follicular architecture in FL, marginal zone-like structure in nMZL)<\/li>\n\n\n\n<li><strong>Lymphoplasmacytic lymphoma<\/strong><br>May have clinically and histologically overlapping features; differentiation by specific immunophenotypes (e.g. absence of CD5, CD10, CD23 in nMZL, but expression of plasma cell markers in LPL)<\/li>\n\n\n\n<li><strong>Mature B-cell lymphomas<\/strong><br>Differentiation using immunohistochemistry (e.g.&nbsp;<strong>CD20+, CD5-, CD10-, CD23-<\/strong>, typical for nMZL)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnosemethodik-2\"><\/span>Diagnostic methodology<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Histological diagnosis by&nbsp;<strong>Lymph node biopsy<\/strong>&nbsp;(diagnosis of exclusion)<\/li>\n\n\n\n<li>Staging according to&nbsp;<strong>Ann Arbor Classification<\/strong><\/li>\n\n\n\n<li><strong>PET-CT<\/strong>,&nbsp;<strong>Bone marrow biopsy<\/strong>,&nbsp;<strong>Blood count<\/strong>,&nbsp;<strong>Pulmonary function tests<\/strong>,&nbsp;<strong>ECG\/heart echo<\/strong>&nbsp;(before therapy)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-3\"><\/span>Therapy<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>First line<\/strong><br><strong>Rituximab + chemotherapy<\/strong>&nbsp;(e.g.&nbsp;&nbsp;<strong>Bendamustine<\/strong>, CVP, CHOP)<\/li>\n\n\n\n<li><strong>Rituximab maintenance therapy<\/strong>&nbsp;(2 years) shows prolonged progression-free survival<\/li>\n\n\n\n<li>In case of recurrence:&nbsp;<br><strong>renewed rituximab\/chemotherapy<\/strong>,&nbsp;<strong>High-dose therapy with autologous stem cell transplantation<\/strong>&nbsp;(for early relapses)<\/li>\n\n\n\n<li>For refractory disease<br><strong>BTK inhibitors (ibrutinib, zanubrutinib)<\/strong>&nbsp;or&nbsp;<strong>PI3K inhibitors (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>Splenic marginal zone lymphoma (SMZL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The <strong>Splenic marginal zone lymphoma (SMZL)<\/strong>&nbsp;is one with approx.&nbsp;<strong>1-2%<\/strong>&nbsp;of all lymphomas; and approx.&nbsp;&nbsp;<strong>2%<\/strong>&nbsp;all MZL, rare, indolent B-cell neoplasia that manifests primarily in the spleen and is often accompanied by involvement of the bone marrow and peripheral blood.&nbsp;<br>The differential diagnosis is difficult due to the lack of specific cellular markers and requires multimodal diagnostics.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_Merkmale-3\"><\/span>Clinical features<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Typical are&nbsp;<strong>Splenomegaly<\/strong>,&nbsp;<strong>Bone marrow infiltration<\/strong>&nbsp;and variable&nbsp;<strong>leukemic involvement<\/strong>&nbsp;of the peripheral blood<br>Generalized lymphadenopathy is rare<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Zytomorphologie\"><\/span>Cytomorphology<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>The peripheral blood contains&nbsp;<strong>lymphatic cells with short, polar villi<\/strong>,&nbsp;<strong>plasmacytoid lymphocytes<\/strong>&nbsp;and inconspicuous lymphocytes.  The cells show a mature, villous morphology<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Histologie\"><\/span>Histology<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>The spleen shows involvement of the white and red pulp, with the white pulp typically being enlarged. The bone marrow shows&nbsp;<strong>micronodular infiltrates<\/strong>&nbsp;of atypical lymphocytes<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Immunphanotyp\"><\/span>Immunophenotype<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The tumor cells express&nbsp;<strong>Pan B cell antigens<\/strong>&nbsp;(CD19, CD20, CD22, CD79a),&nbsp;<strong>sIgM\/IgD<\/strong>&nbsp;and&nbsp;<strong>FMC7<\/strong>, but are&nbsp;<strong>negative for CD5, CD10, CD23, CD43, CD103, Cyclin D1 and Annexin A1<\/strong>.&nbsp;<br>The&nbsp;<strong>Misexpression of CD5<\/strong>&nbsp;is crucial for differentiating between chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL)<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Zytogenetik_und_molekulare_Marker\"><\/span>Cytogenetics and molecular markers<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Deletion 7q<\/strong>In approx.&nbsp;<strong>30-40% of the cases<\/strong>&nbsp;detectable - a characteristic but not specific feature<\/li>\n\n\n\n<li><strong>Trisomy 3q<\/strong>&nbsp;and&nbsp;<strong>Gains of 1q, 8q, 12q, 18<\/strong>&nbsp;are often<\/li>\n\n\n\n<li><strong>Molecular genetic changes<\/strong>: Mutations in&nbsp;<strong>NOTCH2 (10-25%)<\/strong>,&nbsp;<strong>KLF2 (10-40%)<\/strong>,&nbsp;<strong>TP53<\/strong>&nbsp;and&nbsp;<strong>MYD88<\/strong>&nbsp;are frequent and associated with a less favorable course.<\/li>\n\n\n\n<li><strong>No characteristic translocation<\/strong>&nbsp;as in follicular lymphoma (t(14;18)) or mantle cell lymphoma (t(11;14))<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-4\"><\/span>Differential diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Splenic B-cell lymphoma\/leukemia with prominent nucleoli (SBLPN)<\/strong>Mutations in MAP2K1, specific cell morphology<\/li>\n\n\n\n<li><strong>Chronic lymphocytic leukemia (CLL)<\/strong>CD5-positive, CD23-positive, cell morphology different<\/li>\n\n\n\n<li><strong>Mantle cell lymphoma (MCL)<\/strong>CD5-positive, cyclin D1-positive, t(11;14) present<\/li>\n\n\n\n<li><strong>Hairy cell leukemia (HZL)<\/strong>BRAF V600E mutation, \u201ehair cells\u201c in the blood, CD11c-positive<\/li>\n\n\n\n<li><strong>Lymphoplasmocytic lymphoma (LPL)<\/strong>MYD88 L265P mutation, CXCR4 mutation, IgM macroglobulinemia<\/li>\n\n\n\n<li><strong>Splenic diffuse small B-cell lymphoma of the red pulp (SDRPL)<\/strong>: Histologically different, more frequent involvement of the red pulp<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnosemethodik-3\"><\/span><strong>Diagnostic methodology<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Peripheral lymphocyte typing<\/strong>,&nbsp;<strong>Bone marrow biopsy<\/strong>,&nbsp;<strong>Splenectomy preparation<\/strong>&nbsp;(rare)<\/li>\n\n\n\n<li><strong>Immunophenotype<\/strong>:&nbsp;<strong>CD20+, CD79a+, sIgM\/IgD+, CD5-, CD10-, CD23-, CD43-, Annexin A1-, Cyclin D1-<\/strong>.<\/li>\n\n\n\n<li><strong>Ki67 staining<\/strong>:&nbsp;<strong>Targetoid pattern<\/strong>&nbsp;(characteristic)<\/li>\n\n\n\n<li><strong>Molecular genetics<\/strong>:&nbsp;<strong>NOTCH2-<\/strong>&nbsp;(10-25%) and&nbsp;<strong>KLF2-<\/strong>&nbsp;(10-40%) mutations \u2192 less favorable course<\/li>\n\n\n\n<li><strong>Spleen histology<\/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>Therapy<\/strong> and forecast<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Indication for therapy<\/strong><br>Only in case of cytopenia (Hb &lt;10 g\/dl, platelets &lt;80,000, neutrophils &lt;1000) or symptomatic splenomegaly<\/li>\n\n\n\n<li><strong>Therapy options<\/strong><br>- <strong>Splenectomy<\/strong>&nbsp;(equivalent option).<br>- <strong>Rituximab monotherapy<\/strong><br>- or&nbsp;<strong>Rituximab + bendamustine<\/strong>.<\/li>\n\n\n\n<li>Median overall survival &gt;10 years<br><strong>POD24<\/strong>&nbsp;(progression within 24 months) \u2192 median survival 3-5 years<\/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>Primary cutaneous lymphomas (CL)<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Primary cutaneous lymphomas (CL) are a heterogeneous group of lymphoproliferative diseases of the skin characterized by isolated skin involvement without systemic involvement. They account for about&nbsp;<strong>70 %<\/strong>&nbsp;of cutaneous lymphomas (T-cell lymphomas) and&nbsp;<strong>25 %<\/strong>&nbsp;(B-cell lymphomas), with the remaining 5 % including rare forms.  The disease occurs predominantly in middle to old age, with an annual incidence of around&nbsp;<strong>1,000 new cases in Germany<\/strong>.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisch-morphologische_Merkmale-2\"><\/span><strong>Clinical-morphological features<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Most common form<\/strong>:&nbsp;<strong>Mycosis fungoides (MF)<\/strong><br>typically begins with erythematous plaques that develop into scaly, thickened lesions (\u201ecigarette paper\u201c plaques)<br>Later, tumor nodules and generalized involvement may occur<\/li>\n\n\n\n<li><strong>Primary cutaneous B-cell lymphoma (CBCL)<\/strong><br>- <strong>Follicular lymphoma<\/strong>Solitary or few, smooth, red to brown-red plaques on the trunk, face or head. Clinically often&nbsp;<strong>asymptomatic<\/strong><br>- <strong>Marginal zone lymphoma<\/strong>Multiple papules or plaques, often on the leg<br>- <strong>S\u00e9zary syndrome<\/strong>Generalized erythroderma, lymphadenopathy, pruritus, pseudopapillomas,&nbsp;<strong>CD4+\/CD56+<\/strong>-cells in the blood<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnose\"><\/span><strong>Differential diagnosis<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Clinical<\/strong><br>Psoriasis, atopic eczema, chronic contact dermatitis, lichen planus, lupus erythematosus, skin tuberculosis, mycosis fungoides vs. pityriasis rubra pilaris<\/li>\n\n\n\n<li><strong>Histological<\/strong><br>Pseudolymphomas (e.g.&nbsp;<em>Lymphadenosis cutis benigna<\/em>), benign lymphocyte infiltrate, reactive lymphadenopathy, cutis laxa, granulomatous slack skin, subcutaneous panniculitis-like lymphoma<\/li>\n\n\n\n<li><strong>Specific differential diagnoses for CBCL<\/strong><br><strong>Primary cutaneous follicular lymphoma<\/strong>&nbsp;vs. reactive germinal centers,&nbsp;<strong>Marginal zone lymphoma<\/strong>&nbsp;vs. chronic inflammation,&nbsp;<strong>diffuse large cell lymphoma<\/strong>&nbsp;vs. malignant melanoma, Hodgkin's lymphoma, carcinoma<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methoden-3\"><\/span><strong>Diagnostic methods<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Clinical examination<\/strong><br>Detailed medical history, skin and lymph node examination<\/li>\n\n\n\n<li><strong>Histology<\/strong><br>Biopsy with&nbsp;<strong>several levels<\/strong>, preferred for non-eroded lesions<\/li>\n\n\n\n<li><strong>Immunohistochemistry<\/strong><br>CD20, CD79a (B cells), CD3, CD4, CD5, CD7 (T cells), CD30 (for CD30+ diseases), Bcl-2, Bcl-6, CD10<\/li>\n\n\n\n<li><strong>Molecular biology<\/strong><br>- <strong>PCR for clonal immunoglobulin genes<\/strong>&nbsp;(IGK, IGH) - Detection of a clonal tumor cell population<br>- <strong>FISH or cytogenetics<\/strong><br>t(14;18)(q32;q21) in follicular lymphoma (only in approx. 30-50 % of primary cutaneous cases)<\/li>\n\n\n\n<li><strong>Staging<\/strong> - <strong>TNM classification<\/strong>&nbsp;(ISCL\/EORTC):<br>- <strong>T<\/strong> - Size and extent of the skin lesions (T1-T4)<br>- <strong>N<\/strong> - Lymph node involvement (N0-N3)<br>- <strong>M<\/strong> - Systemic infestation (M0-M1)<\/li>\n\n\n\n<li><strong>Imaging<\/strong><br><strong>PET\/CT<\/strong>&nbsp;for the detection of subclinical infestation (recommended for higher stages)<\/li>\n\n\n\n<li><strong>Bone marrow biopsy<\/strong><br>If systemic spread is suspected (e.g. diffuse large cell lymphoma)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-4\"><\/span><strong>Therapy<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Localized lesions (stage I\/II)<\/strong><br>- <strong>Radiotherapy<\/strong>: Permanent local tumor control for&nbsp;<strong>90-100 %<\/strong>&nbsp;the CTCL and&nbsp;<strong>95-100 %<\/strong>&nbsp;of CBCL cases<br>- <strong>Topical therapy<\/strong>: <strong>Nitrogen mustard (mechlorethamine)<\/strong>,&nbsp;<strong>Bexarotene gel<\/strong>&nbsp;(for MF),&nbsp;<strong>Imiquimod<\/strong>,&nbsp;<strong>Corticosteroids<\/strong><\/li>\n\n\n\n<li><strong>Multiplying or locally advanced lesions<\/strong><br>- <strong>Phototherapy<\/strong>UVB, PUVA (for MF)<\/li>\n\n\n\n<li><strong>Systemic therapy<\/strong><br>- <strong>Rituximab<\/strong>&nbsp;(anti-CD20 antibody): Standard for B-cell lymphomas (R-CHOP, R-CVP)<br>- <strong>CHOP scheme<\/strong>&nbsp;(cyclophosphamide, doxorubicin, vincristine, prednisone) or&nbsp;<strong>R-CHOP<\/strong>&nbsp;for aggressive forms<br>- <strong>Brentuximab vedotin<\/strong>&nbsp;(CD30+)<\/li>\n\n\n\n<li><strong>Prophylaxis for S\u00e9zary syndrome<\/strong>Systemic therapy, e.g.&nbsp;<strong>Methotrexate<\/strong>,&nbsp;<strong>Bexarotene<\/strong>,&nbsp;<strong>Alemtuzumab<\/strong>.&nbsp;<\/li>\n\n\n\n<li><strong>Study-based therapy<\/strong>: For early lesions (\u201elow burden\u201c) a&nbsp;<strong>\u201ewait and see\u201c strategy<\/strong>&nbsp;with&nbsp;<strong>Rituximab<\/strong>&nbsp;(RESORT study) to be superior to observation<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-3\"><\/span><strong>Forecast<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Good prognosis (&gt;5 years survival time)<\/strong><br>- Mycosis fungoides (early stages), primarily cutaneous&nbsp;<strong>follicular B-cell lymphoma<\/strong>,&nbsp;<strong>Marginal zone lymphoma<\/strong>,&nbsp;<strong>Lymphomatoid papulosis<\/strong>,&nbsp;<strong>Pagetoid reticulosis<\/strong>.<br>- <strong>5-year survival rate<\/strong>:&nbsp;<strong>up to 95 %<\/strong>&nbsp;for follicular lymphoma without bone marrow involvement<\/li>\n\n\n\n<li><strong>Medium forecast (2-5 years)<\/strong><br>S\u00e9zary syndrome, folliculotropic MF, diffuse large B-cell lymphoma (other types)<\/li>\n\n\n\n<li><strong>Poor prognosis (&lt;2 years)<\/strong><br>Intravascular large B-cell lymphoma,&nbsp;<strong>gamma\/delta T-cell lymphoma<\/strong>,&nbsp;<strong>CD4+\/CD56+<\/strong>-neoplasia,&nbsp;<strong>NK\/T-cell lymphoma<\/strong><\/li>\n\n\n\n<li><strong>Prognostic factors<\/strong><br>Localization on the leg (poorer prognosis), bone marrow infiltration,&nbsp;<strong>Bcl-2 expression<\/strong>,&nbsp;<strong>t(14;18)-negativity<\/strong>,&nbsp;<strong>high LDH<\/strong>,&nbsp;<strong>CD56 positivity<\/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>Notice<\/strong>The prognosis has improved thanks to modern therapies (e.g.&nbsp;<strong>Rituximab<\/strong>,&nbsp;<strong>Immunotherapies<\/strong>), but there is a lack of up-to-date, large-scale statistics that fully reflect these developments.  The&nbsp;<strong>Clonality analysis<\/strong>&nbsp;is an important prognostic factor that has not yet been taken into account in older studies.<\/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>Primary duodenal B-cell lymphoma (MALT type)<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">A primary duodenal B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) is a rare form of malignant non-Hodgkin lymphoma that develops in the duodenum. It originates from B-cells and grows at the expense of mucosal lymphoid tissue.<br>Although rare, it is one of the more common extranodal lymphomas, with the stomach being the most frequent location, followed by the duodenum and other gastrointestinal regions.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">MALT lymphomas are overall&nbsp;<strong>rarely<\/strong>&nbsp;and do about&nbsp;<strong>7\u20138 %<\/strong>&nbsp;all newly diagnosed non-Hodgkin lymphomas. The&nbsp;<strong>The stomach is the most common location<\/strong>&nbsp;(30\u201360 % der MALT-Lymphome), w\u00e4hrend das&nbsp;<strong>Duodenum is clearly less commonly affected<\/strong>&nbsp;is.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">According to current guidelines and studies, MALT lymphomas are found in&nbsp;<strong>entire gastrointestinal tract<\/strong>&nbsp;only approximately&nbsp;<strong>5 % der F\u00e4lle<\/strong>, with the vast majority being localized in the stomach.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Specific incidence data for the duodenum are not available, but it is considered&nbsp;<strong>Rarest location in the small intestine<\/strong>&nbsp;regarded. Estimates suggest that&nbsp;<strong>only about 3 % of all MALT lymphomas in the intestinal tract<\/strong>, and the duodenal portion of that is minimal.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>Incidence of all MALT lymphomas<\/strong>&nbsp;is about&nbsp;<strong>1 case per 313,000 people per year<\/strong>, with a median age of illness of&nbsp;<strong>65 years<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A light&nbsp;<strong>Female dominance<\/strong>&nbsp;is described, in contrast to stomach lymphomas, which tend to affect men.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">primary duodenal MALT lymphoma is a&nbsp;<strong>Indolent, mostly localized disease<\/strong>, which by&nbsp;<strong><em>H. pylori<\/em>Eradication<\/strong>&nbsp;can be treated. The&nbsp;<strong>Diagnosis requires histological and immunohistochemical confirmation<\/strong>, supplemented by&nbsp;<strong>molecular biology and imaging techniques<\/strong>.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_Merkmale-4\"><\/span>Clinical features<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Symptoms<\/strong><br>Often unspecific, like&nbsp;<strong>Fatigue, weight loss, abdominal pain, nausea, or bleeding<\/strong>&nbsp;from the upper gastrointestinal tract<br>In some cases, it may lead to&nbsp;<strong>obstructive symptoms<\/strong>&nbsp;occur if the lymphoma infiltrates the intestinal wall or causes stenosis<\/li>\n\n\n\n<li><strong>Clinical picture<\/strong>The disease usually progresses&nbsp;<strong>lazy<\/strong>, but with progression it can lead to a&nbsp;<strong>Transformation into diffuse large B-cell lymphoma (DLBCL)<\/strong>&nbsp;come. This is considered a clinically unfavorable development.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-5\"><\/span>Differential diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Differential diagnoses include:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Benign inflammatory diseases<\/strong>&nbsp;of the duodenum (e.g., chronic enteritis, Crohn's disease)<\/li>\n\n\n\n<li><strong>Malignant Tumors<\/strong>&nbsp;of the duodenum (e.g., adenocarcinoma, GIST)<\/li>\n\n\n\n<li><strong>Other non-Hodgkin's lymphomas<\/strong>&nbsp;(e.g., DLBCL, follicular lymphoma)<\/li>\n\n\n\n<li><strong>Infections<\/strong>&nbsp;(e.g.&nbsp;<em>Helicobacter pylori<\/em>-associated gastritis, also relevant for duodenal MALT lymphomas)<\/li>\n\n\n\n<li><strong>Autoimmune diseases<\/strong>&nbsp;(e.g., Celiac disease, autoimmune enteritis)&nbsp;<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methoden-4\"><\/span>Diagnostic methods<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Endoscopy with biopsy<\/strong><br>The&nbsp;<strong>Histology<\/strong>&nbsp;shows a&nbsp;<strong>infiltrating lymphocyte population<\/strong>&nbsp;in the mucosa and submucosa, often with&nbsp;<strong>Mantle zone-like structure<\/strong><\/li>\n\n\n\n<li><strong>Immunohistochemistry<\/strong><br>Confirms B-cell genesis:&nbsp;<strong>CD20+, CD79a+, PAX5+<\/strong>,&nbsp;<strong>CD10\u2013<\/strong>,&nbsp;<strong>BCL2+<\/strong>,&nbsp;<strong>MUM1-<\/strong>.&nbsp;&nbsp;<strong>CD5-<\/strong>&nbsp;and&nbsp;<strong>CD23-<\/strong>&nbsp;help differentiate from CLL\/SLL<\/li>\n\n\n\n<li><strong>Clonality analysis<\/strong><br>Proof of&nbsp;<strong>B-cell clonality<\/strong>&nbsp;(e.g., via PCR for IgH gene rearrangements)<\/li>\n\n\n\n<li><strong>Molecular biological investigations<\/strong><br>- <strong>FISH<\/strong><br>Exclusion of translocations such as&nbsp;<strong>t(11;18)(q21;q21)<\/strong>&nbsp;(BIRC3-MALT1), which are associated with therapy resistance<br>- <strong>Gene expression profile<\/strong>: <br>Subclassification by&nbsp;<strong>Cell of Origin (COO)<\/strong>&nbsp;\u2013 GCB-like or ABC-like \u2013 has prognostic relevance<\/li>\n\n\n\n<li><strong>Imaging<\/strong><br>- <strong>CT or MRI abdomen<\/strong>&nbsp;for staging<br>- <strong>FDG-PET\/CT<\/strong>&nbsp;is recommended when advanced stage or transformation is suspected, as MALT lymphomas often&nbsp;<strong>low FDG uptake<\/strong>&nbsp;exhibit<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-5\"><\/span>Therapy<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>First choice in isolated duodenal involvement and evidence of&nbsp;<em>H. pylori<\/em><\/strong>:&nbsp;<strong>Antibiotic therapy for eradication<\/strong>, up to&nbsp;<strong>50\u201370% der F\u00e4lle<\/strong>&nbsp;leads to complete remission&nbsp;<\/li>\n\n\n\n<li><strong>Regarding negative&nbsp;<em>H. pylori<\/em>- Status or therapy resistance<\/strong><br>- <strong>Radiotherapy<\/strong> very effective for localized lesions (e.g., in the duodenum) with high remission rates<br><strong>Chemotherapy<\/strong> in advanced stage or transformation to DLBCL:&nbsp;<strong>R-CHOP<\/strong>&nbsp;(Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone).<br>- <strong>New therapies<\/strong> in case of a relapsed or refractory course:&nbsp;<br>\u2013 \u2013 <strong>BTK inhibitors (e.g., Ibrutinib)<\/strong><br>\u2013 \u2013 <strong>BCL2 inhibitors (e.g., Venetoclax)<\/strong>, especially with&nbsp;<em>H. pylori<\/em>-negative or&nbsp;<em>t(11;18)<\/em>-positive cases.&nbsp;<\/li>\n\n\n\n<li><strong>Surgery<\/strong> Only indicated in complications such as bleeding or perforation, not as curative therapy.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-4\"><\/span>Forecast<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>Prognosis is good with early diagnosis and treatment.<\/strong>, but is unfavorable for transformation or specific genetic markers.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Inexpensive with isolated,&nbsp;<em>H. pylori<\/em>positive lesion<\/strong> 10-year survival rate &gt;&nbsp;<strong>75%<\/strong>.<\/li>\n\n\n\n<li><strong>Unfavorable in transformation to DLBCL<\/strong> \u2013 Significantly worsens; requires aggressive therapy.&nbsp;<\/li>\n\n\n\n<li><strong>Factors for unfavorable prognosis<\/strong>:\n<ul class=\"wp-block-list\">\n<li><strong>t(11;18)(q21;q21)<\/strong>Translocation<\/li>\n\n\n\n<li><strong>CD5 expression<\/strong><\/li>\n\n\n\n<li><strong>Location outside the stomach<\/strong>&nbsp;(e.g., Duodenum)<\/li>\n\n\n\n<li><strong>Stage III\/IV<\/strong><\/li>\n\n\n\n<li><strong>Elevated LDH<\/strong><\/li>\n\n\n\n<li><strong>Number of extranodal organs<\/strong>&nbsp;(after 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>Clinical-morphological features<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Morphology<\/strong><br>Infiltration of the mucosa and submucosa by&nbsp;<strong>small to medium lymphocytes<\/strong>&nbsp;with&nbsp;<strong>centrocentric nuclear shape<\/strong>,&nbsp;<strong>good differentiation<\/strong>,&nbsp;<strong>low proliferation rate (Ki-67 &lt; 10%)<\/strong><\/li>\n\n\n\n<li><strong>Immunophenotype<\/strong><br><strong>CD20+, CD79a+, CD10\u2013, BCL2+, MUM1\u2013, CD5\u2013, CD23\u2013<\/strong><\/li>\n\n\n\n<li><strong>Genetics<\/strong><br><strong>t(11;18)(q21;q21)<\/strong>&nbsp;in 20\u201340% of cases,&nbsp;<strong>t(1;14)(p22;q32)<\/strong>&nbsp;rarely,&nbsp;<strong>BCL10 Translocations<\/strong>&nbsp;possible<\/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>Diffuse large B-cell lymphoma (DLBCL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">The <strong>Diffuse large B-cell lymphoma (DLBCL)<\/strong>&nbsp;is the most common form of non-Hodgkin's lymphoma in adults and is characterized by an aggressive clinical course.&nbsp;<br>It develops from mature B cells and is classified in the current WHO classification (WHO-HAEM5) and the International Consensus Classification (ICC) as&nbsp;<strong>DLBCL, NOS (not elsewhere classified)<\/strong>&nbsp;is defined, whereby a subdivision into molecular subtypes is recommended.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Molekulare_Subtypen_Cell_of_Origin_COO\"><\/span><strong>Molecular subtypes (Cell of Origin, COO)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>GCB-DLBCL (germinal center B-cell-like)<\/strong><br>Similar to the development of B cells in the germinal center<br>Has a better prognosis with a 5-year progression-free survival of&nbsp;<strong>70-80%<\/strong><\/li>\n\n\n\n<li><strong>ABC-DLBCL (activated B-cell-like)<\/strong><br>Similar to activated B cells outside the germinal center<br>Characterized by a less favorable prognosis with a 5-year progression-free survival of&nbsp;<strong>40-50%<\/strong><\/li>\n\n\n\n<li><strong>10-15% of the cases<\/strong>&nbsp;cannot currently be assigned to a subtype<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_Merkmale-5\"><\/span><strong>Clinical features<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Main places of manifestation<\/strong><br>Lymph nodes, spleen, bone marrow, extranodal organs (e.g. gastrointestinal tract, skin)<\/li>\n\n\n\n<li><strong>B symptoms<\/strong>&nbsp;(fever, night sweats, weight loss) are common<\/li>\n\n\n\n<li><strong>Prognostic factors<\/strong><br>Age &gt;60 years, advanced stage (III-IV), elevated LDH, high IPI score, large tumor mass (bulk &gt;7.5 cm), bone marrow infiltration, male gender, vitamin D deficiency<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostische_Abgrenzung\"><\/span><strong>Differential diagnosis<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">DLBCL, NOS must be differentiated from other large B-cell lymphomas, including:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Highly malignant B-cell lymphomas (HGBL) with MYC and BCL2 and\/or BCL6 rearrangements<\/strong><br>(\u201edouble-hit\u201c or \u201etriple-hit\u201c lymphomas), which are considered independent entities<\/li>\n\n\n\n<li><strong>Large B-cell lymphoma with IRF4 rearrangement<\/strong>&nbsp;(definitive entity)<\/li>\n\n\n\n<li><strong>Primary DLBCL of the central nervous system<\/strong>,&nbsp;<strong>of the testicle<\/strong>&nbsp;or&nbsp;<strong>the Vitroretina<\/strong><\/li>\n\n\n\n<li><strong>EBV-positive DLBCL<\/strong>,&nbsp;<strong>KSHV\/HHV8-positive DLBCL<\/strong>,&nbsp;<strong>fibrin-associated DLBCL<\/strong>&nbsp;and&nbsp;<strong>HGBL with 11q aberration<\/strong><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Kriterien\"><\/span><strong>Diagnostic criteria<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The standard diagnostics include:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Histopathological examination<\/strong>&nbsp;of a lymph node biopsy<\/li>\n\n\n\n<li><strong>Immunohistochemistry<\/strong>&nbsp;with marker panel (CD20, CD10, BCL6, MUM1, CD5, CD30, MYC, BCL2)<\/li>\n\n\n\n<li><strong>Gene expression analysis<\/strong>&nbsp;to determine the COO subtype (gold standard, but not a standard service provided by health insurance companies)<\/li>\n\n\n\n<li><strong>Cytogenetics and molecular genetic analyses<\/strong>&nbsp;(MYC, BCL2, BCL6 translocations, mutations in EZH2, MYD88, CARD11, CREBBP)<\/li>\n\n\n\n<li><strong>Imaging<\/strong>&nbsp;(CT, PET-CT) and&nbsp;<strong>Bone marrow examination<\/strong>&nbsp;to the staging<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie_und_Prognose-3\"><\/span><strong>Therapy<\/strong> and forecast<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>First-line therapy<\/strong><br><strong>R-CHOP scheme<\/strong>&nbsp;(rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) for patients with low to intermediate risk<\/li>\n\n\n\n<li><strong>Alternatives<\/strong><br><strong>Pola-R-CHP<\/strong>&nbsp;(with polatuzumab vedotin) for intermediate to high risk<\/li>\n\n\n\n<li><strong>Recurrent\/refractory<\/strong><br><strong>CAR-T cell therapy<\/strong>&nbsp;(e.g. tisagenlecleucel, axicabtagen-ciloleucel),&nbsp;<strong>Bispecific antibodies<\/strong>&nbsp;(epcoritamab, glofitamab, odronextamab),&nbsp;<strong>Loncastuximab tesirine<\/strong>&nbsp;or&nbsp;<strong>autologous stem cell transplantation<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">If left untreated, DLBCL quickly becomes lethal, but with modern therapies, up to&nbsp;<strong>70% of patient healing<\/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>Primary mediastinal B-cell lymphoma (pMBCL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Primary mediastinal B-cell lymphoma (PMBCL)<\/strong>&nbsp;is a rare, aggressive subtype of non-Hodgkin's lymphoma (NHL), which affects approx.&nbsp;&nbsp;<strong>2-4 accounts for % of all NHLs<\/strong>&nbsp;and above all&nbsp;<strong>young women aged 30-40 on average<\/strong>&nbsp;(median age of onset around 35 years).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Originally classified as a subtype of diffuse large B-cell lymphoma (DLBCL), it has been listed as an independent entity in the WHO classification since 2001, as it is distinguished by specific clinical, pathological and molecular characteristics.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_Prasentation\"><\/span>Clinical presentation<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">PMBCL is created in the&nbsp;<strong>anterior mediastinum<\/strong>&nbsp;(between the lungs, behind the sternum) and leads to typical symptoms such as the local invasive growth:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Upper influence accumulation<\/strong>&nbsp;(e.g. visible vein in the thoracic wall),<\/li>\n\n\n\n<li><strong>Airway compression<\/strong>&nbsp;or obstruction,<\/li>\n\n\n\n<li><strong>Esophageal constriction<\/strong>,<\/li>\n\n\n\n<li><strong>Pericardial tamponade<\/strong>,<\/li>\n\n\n\n<li><strong>Thrombosis of the cervical veins<\/strong>,<\/li>\n\n\n\n<li><strong>Pleural effusions<\/strong>,<\/li>\n\n\n\n<li><strong>Tumor lysis syndrome<\/strong>&nbsp;(rare).<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Laboratory chemistry often shows a&nbsp;<strong>Increased lactate dehydrogenase (LDH)<\/strong>&nbsp;and&nbsp;<strong>B symptoms<\/strong>&nbsp;(fever, night sweats, weight loss) in about half of the patients.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Pathogenese_und_Diagnostik\"><\/span>Pathogenesis and diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">PMBCL differs significantly from other DLBCL subtypes at the molecular level:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Constitutive activation of the NF-\u03baB and JAK\/STAT signaling pathway<\/strong><\/li>\n\n\n\n<li><strong>Frequent amplification of the 9p24.1 locus<\/strong>&nbsp;with overexpression of&nbsp;<strong>PD-L1 and PD-L2<\/strong>&nbsp;- a central reason for the effectiveness of&nbsp;<strong>PD-1 inhibitors<\/strong>&nbsp;like&nbsp;<strong>Pembrolizumab<\/strong>&nbsp;and&nbsp;<strong>Nivolumab<\/strong><\/li>\n\n\n\n<li><strong>CD30 positivity<\/strong>&nbsp;(similar to classic Hodgkin's lymphoma)<\/li>\n\n\n\n<li><strong>No immunoglobulins<\/strong>&nbsp;(in contrast to other B-cell lymphomas)<\/li>\n\n\n\n<li><strong>Similarity to Reed-Sternberg cells<\/strong>&nbsp;of classical Hodgkin's lymphoma (cHL), which makes diagnosis more difficult<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The diagnosis is based on a&nbsp;<strong>Lymph node biopsy<\/strong>&nbsp;with histological, immunohistochemical and molecular biological analysis.<br><strong>Circulating tumor DNA (ctDNA)<\/strong>&nbsp;is being investigated as a new biomarker in diagnostics and follow-up.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie_und_Prognose-4\"><\/span>Therapy and prognosis<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>First-line therapy<\/strong><br>Combination of&nbsp;<strong>R-CHOP<\/strong>&nbsp;(rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and&nbsp;<strong>Irradiation<\/strong>&nbsp;of the mediastinum<br>often supplemented by&nbsp;<strong>Etoposide<\/strong>&nbsp;(e.g. R-CHOP-Plus reference programs).<\/li>\n\n\n\n<li><strong>Recurrent\/refractory<\/strong><br>PD-1 inhibitors (e.g.&nbsp;<strong>Pembrolizumab<\/strong>,&nbsp;<strong>Nivolumab<\/strong>) are established and ready for approval<br><strong>Brentuximab vedotin<\/strong>&nbsp;(anti-CD30 antibody-drug conjugate) and&nbsp;<strong>CAR T-cell therapies<\/strong>&nbsp;(e.g.&nbsp;&nbsp;<strong>Axicabtagen Ciloleucel<\/strong>) offer promising options in the second and third lines<\/li>\n\n\n\n<li><strong>Long-term remission<\/strong><br>With initial therapy, the&nbsp;<strong>Survival rate over 90 %<\/strong><br>Poor prognosis in case of recurrence or refractoriness&nbsp;<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-6\"><\/span>Differential diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Important differential diagnoses are<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Classical Hodgkin's lymphoma<\/strong>&nbsp;(similar molecular profiles, but different cell types)<\/li>\n\n\n\n<li><strong>Diffuse large B-cell lymphoma (DLBCL, NOS)<\/strong><\/li>\n\n\n\n<li><strong>High-grade B-cell lymphoma (HGBL)<\/strong>&nbsp;with MYC and BCL2 rearrangement (\u201edouble-hit lymphoma\u201c)<\/li>\n\n\n\n<li><strong>Thymus carcinoma<\/strong>&nbsp;or&nbsp;<strong>Thymoma<\/strong>&nbsp;(especially in the mediastinum)<\/li>\n\n\n\n<li><strong>Lymph node metastases from other tumors<\/strong>&nbsp;(e.g. bronchial carcinoma)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The demarcation is made by&nbsp;<strong>Immunohistochemistry<\/strong>,&nbsp;<strong>cytogenetic examinations<\/strong>&nbsp;(e.g. FISH for 9p24.1 amplification) and&nbsp;<strong>Transcriptome analyses<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">PMBCL is a rare, but well-treatable, aggressive B-cell lymphoma with a characteristic localization in the mediastinum, typical clinical symptoms and a specific molecular profile that&nbsp;<strong>Targeted therapies<\/strong>&nbsp;like&nbsp;<strong>PD-1 inhibitors<\/strong>&nbsp;and&nbsp;<strong>CAR-T cells<\/strong>&nbsp;makes it possible.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"BL\"><span class=\"ez-toc-section\" id=\"Burkitt-Lymphom_BL\"><\/span><strong>Burkitt's lymphoma (BL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Burkitt's lymphoma (BL) is a highly malignant, aggressive B-cell non-Hodgkin's lymphoma with&nbsp;<strong>extraordinarily high cell division rate<\/strong>&nbsp;and a proliferation rate of almost 100 1TP3.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_Merkmale-6\"><\/span><strong>Clinical features<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Morphologically it shows a&nbsp;<strong>Diffuse, purely blastic infiltrate<\/strong>&nbsp;from medium-sized cells with&nbsp;<strong>round, basophilic nuclei<\/strong>,&nbsp;<strong>several Nucleoli<\/strong>&nbsp;and a&nbsp;<strong>characteristic, basophilic cytoplasm with vacuolization<\/strong>.  A typical histological feature is the&nbsp;<strong>\u201eStarry sky\u201c pattern<\/strong>, generated by&nbsp;<strong>light-colored macrophages<\/strong>, which phagocytose apoptotic tumor cells.  Clinically, a distinction is made between three variants:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Endemic BL<\/strong>Common in Africa, Brazil and Papua New Guinea; mostly in the&nbsp;<strong>Jaw or facial bones<\/strong>&nbsp;manifested, mostly in children.&nbsp;&nbsp;<strong>&gt;95 % EBV-associated<\/strong><\/li>\n\n\n\n<li><strong>Sporadic BL<\/strong>: Worldwide, especially in children and young adults; typical&nbsp;<strong>abdominal manifestation<\/strong>&nbsp;(ileocecal valve, mesentery), can lead to intestinal obstruction.&nbsp;&nbsp;<strong>~20 % EBV-associated<\/strong><\/li>\n\n\n\n<li><strong>Immunodeficiency-associated BL<\/strong>Common in HIV infection (AIDS-defining illness), with&nbsp;<strong>nodal participation<\/strong>&nbsp;and&nbsp;<strong>Bone marrow infiltration<\/strong><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-7\"><\/span><strong>Differential diagnosis<\/strong>tic<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>High-grade B-cell lymphoma (HGBL) with MYC and BCL2 and\/or BCL6 translocations<\/strong><br>(\u201edouble-hit\u201c lymphoma)<br>overlaps clinically and biologically with BL<br><strong>Poorer prognosis<\/strong><\/li>\n\n\n\n<li><strong>Acute lymphoblastic leukemia (ALL) L3 form<\/strong><br>(Burkitt's leukemia), if bone marrow involvement &gt;25 % is present<\/li>\n\n\n\n<li><strong>Diffuse large B-cell lymphoma (DLBCL)<\/strong><br>especially with MYC rearrangement, but without the typical genetics and morphology of BL<\/li>\n\n\n\n<li><strong>Lymphoproliferative diseases in immunocompromised patients<\/strong>&nbsp;<br>(e.g. after transplantation)<br>may show similar EBV-associated patterns<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methoden-5\"><\/span><strong>Diagnostic methods<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cytomorphology<\/strong><br>Bone marrow smear and tissue biopsy show characteristic blastic cells with a \u201estarry sky\u201c pattern<\/li>\n\n\n\n<li><strong>Immunophenotyping<\/strong><br>Positive for&nbsp;<strong>CD19, CD20, CD10, CD38, CD43, CD81, FMC-7, MYC<\/strong><br>Negative for&nbsp;<strong>BCL2, CD44, TdT, CD34<\/strong><\/li>\n\n\n\n<li><strong>Chromosome analysis<\/strong><br>Proof of the&nbsp;<strong>Translocation t(8;14)(q24;q32)<\/strong>&nbsp;(85 %), more rarely t(2;8) or t(8;22)<\/li>\n\n\n\n<li><strong>FISH<\/strong><br>By default&nbsp;<strong>MYC rearrangement<\/strong>&nbsp;(with IGH::MYC* or MYC-independent probe).&nbsp;&nbsp;<strong>11q23\/11q24 probe<\/strong>&nbsp;helps to differentiate against HGBL11q<br>* Molecular genetic notation \u201e::\u201c to indicate a&nbsp;<strong>Gene fusion or rearrangement<\/strong> to symbolize;<br>here the fusion of the MYC oncogene with the IGH gene<\/li>\n\n\n\n<li><strong>Molecular genetics<\/strong>: Mutations in&nbsp;<strong>ID3, MYC, TP53, FOXO1<\/strong>&nbsp;(especially with EBV-negative BL)<\/li>\n\n\n\n<li><strong>Imaging<\/strong>:&nbsp;<strong>PET-CT<\/strong>&nbsp;(high FDG uptake),&nbsp;<strong>MRI<\/strong>&nbsp;with CNS involvement<\/li>\n\n\n\n<li><strong>Cerebrospinal fluid examination<\/strong>: Mandatory due to high probability of CNS involvement<\/li>\n\n\n\n<li><strong>LDH level<\/strong>:&nbsp;<strong>&gt;500 U\/L<\/strong>&nbsp;is a risk factor<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-6\"><\/span><strong>Therapy<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The treatment is&nbsp;<strong>emergency<\/strong>&nbsp;to initiate:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>First-line therapy<\/strong><br>Intensive, short chemotherapy with&nbsp;<strong>Rituximab<\/strong><br>(e.g.&nbsp;&nbsp;<strong>R-CODOX-M\/R-IVAC<\/strong>&nbsp;or&nbsp;<strong>GMALL-B-ALL\/NHL protocol<\/strong>)<\/li>\n\n\n\n<li><strong>Prophylaxis of the CNS<\/strong><br>Intrathecal and systemic&nbsp;<strong>Methotrexate<\/strong><\/li>\n\n\n\n<li><strong>Tumor lysis syndrome prophylaxis<\/strong><br>Intravenous hydration,&nbsp;<strong>Allopurinol or rasburicase<\/strong>&nbsp;(contraindicated for G6PD deficiency!)<\/li>\n\n\n\n<li><strong>Salvage therapy<\/strong><br>In the event of recurrence or treatment failure&nbsp;<strong>autologous stem cell transplantation<\/strong>&nbsp;(limited prospects of success)<\/li>\n\n\n\n<li><strong>Rare indications<\/strong><br>Radiotherapy or surgical intervention for complicated symptoms (e.g. bowel obstruction).&nbsp;<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-5\"><\/span><strong>Forecast<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>In&nbsp;<strong>resource-rich countries<\/strong><br><strong>Overall survival &gt;80 % in adults, &gt;90 % in children<\/strong>&nbsp;under modern immunochemotherapies (e.g. with rituximab)<\/li>\n\n\n\n<li>In countries with&nbsp;<strong>low resources<\/strong><br>Prognosis significantly worse due to delays in diagnosis and treatment<\/li>\n\n\n\n<li><strong>BL-IPI (International Prognostic Index)<\/strong><br>Helps with risk assessment (e.g. LDH, stage, age, CNS involvement)<\/li>\n\n\n\n<li><strong>Molecular genetic subgroups<\/strong><br>(e.g. with TP53, ID3 or FOXO1 mutations) influence the course of the disease<\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"LBL\"><span class=\"ez-toc-section\" id=\"Lymphoblastisches_Lymphom_BL\"><\/span>Lymphoblastic lymphoma (BL)<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">The differential diagnosis of lymphoblastic lymphoma (BL) requires careful differentiation from other B-cell neoplasms, particularly&nbsp;<strong>Burkitt's lymphoma (BL)<\/strong>, dem&nbsp;<strong>diffuse large B-cell lymphoma (DLBCL)<\/strong>&nbsp;and the&nbsp;<strong>B-cell acute lymphoblastic leukemia (B-ALL)<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The clinico-morphological, immunophenotypic, and molecular genetic characteristics are crucial for correct classification.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisch-morphologische_Merkmale-4\"><\/span><strong>Clinical-morphological features<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cytomorphology<\/strong><br>At the&nbsp;<strong>Burkitt's lymphoma<\/strong>&nbsp;show the cells medium-sized, blastular forms with&nbsp;<strong>deep basophilic cytoplasm<\/strong>,&nbsp;<strong>characteristic vacuolization<\/strong>,&nbsp;<strong>round cores<\/strong>&nbsp;and&nbsp;<strong>multiple basophilic nucleoli<\/strong><br>The cell division rate is extremely high.<\/li>\n\n\n\n<li><strong>Cell size and cell cytoplasm<\/strong><br>Unlike B-ALL, the cells in BL&nbsp;<strong>not small<\/strong>, but medium-sized, and show&nbsp;<strong>No significant changes in cell cytoplasm<\/strong>&nbsp;like at the ALL<\/li>\n\n\n\n<li><strong>Proliferation Index<\/strong><br><strong>Ki67 &gt; 95%%<\/strong>&nbsp;\u2013 a central marker for high cell proliferation in BL<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-8\"><\/span><strong>Differential diagnostics<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Facing B-ALL<\/strong><br><strong>\u2013 Missing expression of immature markers<\/strong>BL is&nbsp;<strong>CD34- and TdT-negative<\/strong>,<br>during B-ALL&nbsp;<strong>CD34+ and TdT+<\/strong>&nbsp;is<\/li>\n\n\n\n<li>- <strong>Light chain expression<\/strong>BL shows&nbsp;<strong>Concentrated light chain expression (kappa\/lambda)<\/strong>,<br>what is missing in B-ALL<\/li>\n\n\n\n<li><strong>Opposite DLBCL<\/strong><br>- <strong>MYC rearrangement<\/strong>On the BL is&nbsp;<strong>MYC Translocation (t(8;14), t(8;22), t(2;8))<\/strong>&nbsp;central, <br>but&nbsp;<strong>not specific<\/strong>&nbsp;\u2013 it also occurs in DLBCL<br>- <strong>Karyotype<\/strong>BL shows&nbsp;<strong>less complex karyotypes<\/strong>&nbsp;as DLBCL<br>- <strong>Immunophenotype<\/strong><br>BL is&nbsp;<strong>CD10+, CD19+, CD20+, CD38+++, CD81+++, CD43+, MYC+++<\/strong>, but&nbsp;<strong>BCL2-, CD5-, CD44-, CD138-<\/strong><\/li>\n\n\n\n<li><strong>Opposite HGBL with 11q aberrations<\/strong><br>The entity&nbsp;<strong>HGBL with 11q aberration (HGBL11q)<\/strong>&nbsp;was redefined by the WHO in 2022 and is characterized by&nbsp;<strong>11q23\/11q24 changes<\/strong>&nbsp;from<br>It differs molecularly from classic BL (e.g., through mutations in&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>Diagnostic methods<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cytomorphology<\/strong>&nbsp;Mandatory<\/li>\n\n\n\n<li><strong>Immunophenotyping (Flow Cytometry)<\/strong><br><strong>EDTA or heparin<\/strong>&nbsp;as an anticoagulant. Detection of&nbsp;<strong>CD19+, CD20+, CD10+, CD38++, CD81+++, CD43+, MYC+++<\/strong>,&nbsp;<strong>BCL2-<\/strong><\/li>\n\n\n\n<li><strong>FISH<\/strong> Mandatory<br>Proof of&nbsp;<strong>MYC Rearrangements<\/strong>&nbsp;(IG::MYC-Probe) and&nbsp;<strong>11q-aberrations<\/strong>&nbsp;(11q23\/24 Probe)<br>Distinction between&nbsp;<strong>BL, HGBL11q, and DLBCL\/HGBL-MYC\/BCL2<\/strong><\/li>\n\n\n\n<li><strong>Molecular genetics<\/strong><br>Analyses of&nbsp;<strong>ID3, TP53, FOXO1, MYC<\/strong>.&nbsp;<strong>Missing BCL2 rearrangement<\/strong>&nbsp;at BL<br>unlike HGBL<\/li>\n\n\n\n<li><strong>Chromosome analysis<\/strong><br><strong>Heparin<\/strong>&nbsp;(Recommended as an anticoagulant for cultivation), confirmation of complex changes<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-7\"><\/span><strong>Therapy<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Standard therapy<\/strong><br><strong>Intensive Immunochemotherapy<\/strong>&nbsp;(e.g.&nbsp;&nbsp;<strong>R-CODOX-M\/IVAC<\/strong>,&nbsp;<strong>DA-EPOCH-R<\/strong>) with&nbsp;<strong>Rituximab<\/strong><\/li>\n\n\n\n<li><strong>CNS prophylaxis<\/strong><br><strong>Necessary<\/strong>&nbsp;due to high CNS involvement<\/li>\n\n\n\n<li><strong>Targeted therapies<\/strong><br>Investigated in clinical studies:&nbsp;<strong>BCL2 inhibitors (Venetoclax)<\/strong>,&nbsp;<strong>BTK Inhibitors (Ibrutinib)<\/strong>,&nbsp;<strong>BCL6 Inhibitors<\/strong>,&nbsp;<strong>PI3K inhibitors<\/strong><\/li>\n\n\n\n<li><strong>Stem cell transplantation<\/strong><br>In case of recurrence or high-risk cases<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-6\"><\/span><strong>Forecast<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Adults<\/strong><br><strong>Overall survival &gt; 80%<\/strong>&nbsp;with modern therapy in resource-rich countries.<\/li>\n\n\n\n<li><strong>Children<\/strong><br><strong>Over 90%<\/strong>&nbsp;5-year survival.&nbsp;<\/li>\n\n\n\n<li><strong>Prognostic factors<\/strong>:<br>- <strong>BL-IPI (Burkitt Lymphoma International Prognostic Index)<\/strong>Considers age, stage, LDH, general condition, extranodal involvement<br>- <strong>Molecular subgroups<\/strong> -&nbsp;<strong>EBV-negative BL<\/strong>&nbsp;with&nbsp;<strong>TP53 or ID3 mutations<\/strong>&nbsp;shows a poorer prognosis<br>- <strong>CNS involvement<\/strong>&nbsp;and&nbsp;<strong>high LDH<\/strong>&nbsp;are unfavorable factors<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The correct diagnosis requires a&nbsp;<strong>integrated approach<\/strong>&nbsp;from&nbsp;<strong>Morphology, Immunophenotyping, FISH, and Molecular Genetics<\/strong>, to differentiate Burkitt lymphoma from other aggressive B-cell lymphomas and enable precise therapy.<\/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>Primary cutaneous diffuse large B-cell lymphoma, leg type (DLBCL, LT)<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>Primary cutaneous diffuse large B-cell lymphoma, leg type (DLBCL, LT)<\/strong> is a&nbsp;<strong>aggressive primary cutaneous lymphoma with poor prognosis<\/strong>, which by&nbsp;<strong>specific clinical, histological, and molecular biological features<\/strong>&nbsp;is characterized and primarily manifests in the legs.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The diagnosis requires a&nbsp;<strong>comprehensive staging diagnostics<\/strong>, and the therapy is based on&nbsp;<strong>R-CHOP<\/strong>&nbsp;as default.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The prognosis is moderate despite therapy, which is why early and intensive treatment is crucial.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It differs significantly from indolent forms such as primary cutaneous marginal zone lymphoma (PCMZL) or primary cutaneous follicle center lymphoma (PCFCL) in terms of clinical, histological, and prognostic features.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_Merkmale-7\"><\/span>Clinical features<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Localization<\/strong><br>Typically&nbsp;<strong>individually or in groups on one or both legs<\/strong><\/li>\n\n\n\n<li><strong>Appearance<\/strong><br><strong>Dark erythematous to livid, hard, indurated tumors<\/strong>, which present as plaques or nodules<\/li>\n\n\n\n<li><strong>Course<\/strong><br>Aggressive, with&nbsp;<strong>faster growth rate<\/strong>&nbsp;and high risk of recurrence<\/li>\n\n\n\n<li><strong>Systemic symptoms<\/strong><br>In advanced stages, B symptoms (fever, night sweats, weight loss) may occur<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisch-morphologische_Merkmale-5\"><\/span>Clinical-morphological features<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Histology<\/strong><br>Diffuse infiltrate of large, mature B-cells with&nbsp;<strong>nuclear features such as large cell size, large nucleoli, and numerous mitoses<\/strong>.&nbsp;<\/li>\n\n\n\n<li><strong>Immunohistochemistry<\/strong>e<br>- <strong>Positive for<\/strong> CD20, CD79a, CD10 (in part), Bcl-6, MUM1\/IRF4<br>- <strong>Negative for<\/strong> CD5, CD10 (typically), Bcl-2 (typically negative, in contrast to systemic DLBCL)&nbsp;<\/li>\n\n\n\n<li><strong>Molecular biology<\/strong><br>Common mutations in&nbsp;<strong>Bcl-2, MYD88, MALT-1, Myc, and INK4<\/strong>, promotes cell death resistance and cell cycle dysregulation.<br>However, the pathogenesis is not yet fully understood<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-9\"><\/span>Differential diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The differential diagnosis is crucial, as DLBCL, LT can be confused clinically and histologically with other skin tumors or lymphoproliferative disorders:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Reactive B-cell pseudolymphoma<\/strong><br>Similar histological images, but&nbsp;<strong>no clonal immunoglobulin rearrangement<\/strong>, no systemic involvement<\/li>\n\n\n\n<li><strong>Systemic DLBCL with primary cutaneous involvement<\/strong><br>Must go through&nbsp;<strong>Spread diagnostics<\/strong>&nbsp;(CT, PET-CT, bone marrow) can be ruled out<\/li>\n\n\n\n<li><strong>Other cutaneous lymphomas<\/strong><br>DLBCL, PT must&nbsp;<strong>PCFCL<\/strong>,&nbsp;<strong>PCMZL<\/strong>&nbsp;and&nbsp;<strong>intravascular large B-cell lymphoma<\/strong>&nbsp;to be delimited<\/li>\n\n\n\n<li><strong>Other malignant skin tumors<\/strong><br>Melanoma, carcinoma, and sarcoma are differentiated by immunohistochemistry (e.g., S100, HMB-45, desmin)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methoden-7\"><\/span>Diagnostic methods<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Biopsy<\/strong><br><strong>Atraumatic, sufficiently large punch biopsy<\/strong>&nbsp;for histological, immunohistochemical, and molecular biological investigations<\/li>\n\n\n\n<li><strong>Immunohistochemistry<\/strong><br>Proof of&nbsp;<strong>CD20, CD79a, Bcl-6, MUM1\/IRF4<\/strong>, Exclusion of CD5, CD10<\/li>\n\n\n\n<li><strong>Molecular biology<\/strong><br>Proof of&nbsp;<strong>Clonal immunoglobulin heavy chain rearrangement<\/strong><\/li>\n\n\n\n<li><strong>Spread diagnostics<\/strong><br>- <strong>Lab chemistry<\/strong> \u2013 Blood count, liver and kidney function, LDH<br>- <strong>Imaging<\/strong> - <strong>PET-CT<\/strong>&nbsp;or&nbsp;<strong>CT<\/strong>&nbsp;of the thorax, abdomen, and pelvis<br>- <strong>Bone marrow biopsy<\/strong> - <strong>Mandatory for DLBCL, LT<\/strong>&nbsp;due to the aggressive course<br>- <strong>Lymph node examination<\/strong> Cervical and axillary lymph nodes&nbsp;<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-8\"><\/span>Therapy<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>First-line therapy<\/strong><br><strong>R-CHOP scheme<\/strong>&nbsp;(Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone)<\/li>\n\n\n\n<li><strong>alternative<\/strong><br>Other polychemotherapies with rituximab, if applicable&nbsp;<strong>Stem cell transplantation<\/strong>&nbsp;in case of relapse or refractory disease<\/li>\n\n\n\n<li><strong>Local therapy<\/strong><br>In the case of solitary lesions \u2013&nbsp;<strong>Radiation therapy<\/strong>&nbsp;or&nbsp;<strong>Total excision<\/strong>, but only as&nbsp;<strong>Adjunction<\/strong>, not only in DLBCL, LT<\/li>\n\n\n\n<li><strong>Systemic therapy<\/strong><br>In cases of multiple or disseminated lesions \u2013 <strong>Intravenous rituximab<\/strong>&nbsp;in combination with chemotherapy<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-7\"><\/span>Forecast<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>5-year survival rate<\/strong><br><strong>approx. 55 %<\/strong>&nbsp;\u2013 clearly worse than with indolent forms<\/li>\n\n\n\n<li><strong>Factors with an unfavorable prognosis<\/strong><br>Over 60 years old, high LDH, bone marrow involvement, high tumor stage (T3\/T4), absent CD10 expression<\/li>\n\n\n\n<li><strong>Recurrence rate<\/strong><br>High,&nbsp;<strong>40-50 % of patients suffer relapses<\/strong><\/li>\n\n\n\n<li><strong>Follow-up care<\/strong><br>Regular check-ups (e.g., every 3 months in the first 3 years, then every 6 months) with clinical examination, laboratory tests, and imaging as needed<\/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>Gray areas\/borderline cases<\/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>Diffuse large B-cell lymphoma, NOS (DLBCL, NOS)<\/strong>&nbsp;and&nbsp;<strong>Burkitt's lymphoma (BL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The <strong>Diffuse large B-cell lymphoma, NOS<\/strong>&nbsp;and&nbsp;<strong>Burkitt's lymphoma (BL)<\/strong>&nbsp;are both aggressive B-cell lymphomas with overlapping morphological and immunophenotypic features, making precise differentiation necessary.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The current WHO classification 2022 has clarified differentiation by defining specific genetic markers as crucial for classification.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_und_morphologisches_Bild\"><\/span>Clinical and Morphological Picture<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>DLBCL, NOS<\/strong><br>Typically, it shows a&nbsp;<strong>diffuse, large-cell infiltration<\/strong>&nbsp;with centroblastic, immunoblastic, or anaplastic cells<br>The cells are medium to large, with loose chromatin and prominent nucleoli.&nbsp;<strong>Necrosis<\/strong>&nbsp;are often<br>The clinical picture includes lymph node involvement, spleen and bone marrow infiltration, as well as B symptoms (fever, night sweats, weight loss).<br>Extranodal manifestations are not uncommon<\/li>\n\n\n\n<li><strong>Burkitt's lymphoma<\/strong><br>Characterized by a&nbsp;<strong>extremely high proliferation rate<\/strong>&nbsp;(Ki67 &gt;95 %), an&nbsp;<strong>\u201eStarry-sky pattern<\/strong>&nbsp;due to macrophages in the tumor mass and&nbsp;<strong>small, homogeneous blasts<\/strong>&nbsp;with little cytoplasm<br>It often occurs extranodally (e.g., in the abdominal cavity, bone marrow, CNS) and is associated with a rapid, life-threatening course.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_Methodik\"><\/span>Differential Diagnosis and Methodology<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The differentiation is based on a&nbsp;<strong>multimodal diagnostics<\/strong>, as there are morphological similarities:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cytomorphology &amp; Histology<\/strong><br>The&nbsp;<strong>Cytomorphology<\/strong>&nbsp;is the first step.<br>BL typically shows&nbsp;<strong>small, homogeneous blasts<\/strong>, while DLBCL, NOS shows larger, heterogeneous cells.<br>The&nbsp;<strong>Bone marrow cytology<\/strong>&nbsp;is essential, as infiltrations can be discordant with lymph node involvement.&nbsp;<\/li>\n\n\n\n<li><strong>Immunophenotyping (Immunohistochemistry)<\/strong><br>- <strong>DLBCL, NOS<\/strong><br>Positive for&nbsp;<strong>CD20, CD19, CD79a, PAX5, CD10 (30\u201350 %)<\/strong>,&nbsp;<strong>BCL6 (75\u201389 %)<\/strong>,&nbsp;<strong>MUM1\/IRF4 (17\u201342 %)<\/strong><br><strong>BCL2<\/strong>&nbsp;and&nbsp;<strong>MYC<\/strong>&nbsp;are expressed in many cases (\u201edouble-expresser\u201c phenotype)<br>- <strong>Burkitt's lymphoma<\/strong><br>Positive for&nbsp;<strong>CD20, CD19, CD79a, PAX5, CD10, BCL6, CD56, LMO2<\/strong><br><strong>BCL2 negative<\/strong><br><strong>MYC highly expressed<\/strong><br><strong>TdT positive<\/strong>&nbsp;in up to 2 % of cases<\/li>\n\n\n\n<li><strong>Genetic and Molecular Diagnostics<\/strong><br>- <strong>FISH (fluorescence in situ hybridization)<\/strong><br>the crucial difference:<br>\u2013 \u2013 <strong>DLBCL, NOS<\/strong><br>\u2013 \u2013 \u2013 <strong>No MYC-BCL2 rearrangement<\/strong><br>\u2013 \u2013 \u2013 <strong>MYC rearrangement alone<\/strong>&nbsp;(up to 14 %) is possible, but no indication of BL<br>\u2013 \u2013 <strong><strong>Burkitt's lymphoma<\/strong><\/strong><br>\u2013 \u2013 \u2013 <strong><strong>Typical translocation t(8;14)(q24;q32)<\/strong>&nbsp;\u2192&nbsp;<strong>MYC translocation with IGH<\/strong><\/strong><br>\u2013 \u2013 \u2013 <strong>Additionally, a&nbsp;<strong>double translocation (t(8;14);t(2;8))<\/strong>&nbsp;appearance<\/strong><br>- <strong>Gene expression analysis (gold standard for COO)<\/strong><br>Is used to determine the&nbsp;<strong>Cell of Origin<\/strong>-Subtypes (GCB vs. ABC), however&nbsp;<strong>no statutory benefits from health insurance providers<\/strong><br>GCB subtype shows similar genes to germinal center B cells, ABC subtype resembles activated B cells<br>- <strong>Molecular genetics<\/strong><br>BL shows typical mutations in&nbsp;<strong>ID3, CCND3, TP53<\/strong><br>DLBCL, NOS often shows&nbsp;<strong>CREBBP, EZH2, KMT2D, TP53<\/strong>&nbsp;on<\/li>\n\n\n\n<li><strong>Differentiation of High-Grade B-Cell Lymphomas (HGBL)<\/strong><br>- <strong>HGBL with MYC and BCL2 rearrangement (\u201edouble-hit\u201c)<\/strong><br>Is&nbsp;<strong>no longer part of DLBCL, NOS<\/strong>, but rather a separate entity.<br><strong>Prognosis unfavorable<\/strong><br>requires intensive therapy<br>- <strong>HGBL with 11q aberration<\/strong><br><strong>MYC-Rearrangement negative<\/strong>, but&nbsp;<strong>11q23.3 gain and 11q24.1-qter loss<\/strong><br>Morphology and immunophenotype are similar to BL, but&nbsp;<strong>BCL2 negative<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">A&nbsp;<strong>experienced hematopathologist<\/strong>&nbsp;and&nbsp;<strong>Reference pathology<\/strong>&nbsp;are recommended!<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-9\"><\/span>Therapy<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>DLBCL, NOS<\/strong><br>Standard therapy is&nbsp;<strong>R-CHOP<\/strong>&nbsp;(Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone)<br>With&nbsp;<strong>Recurrence or refractoriness<\/strong>&nbsp;are&nbsp;<strong>CAR T-cell therapies<\/strong>&nbsp;(e.g., Axicabtagene ciloleucel) approved<\/li>\n\n\n\n<li><strong>Burkitt's lymphoma<\/strong><br>Requires&nbsp;<strong>intensive, short chemotherapies<\/strong>&nbsp;(e.g.&nbsp;&nbsp;<strong>CODOX-M\/IVAC<\/strong>as the tumor cells proliferate very rapidly<br><strong>Rituximab<\/strong>&nbsp;is integrated (R-CODOX-M\/IVAC)<br><strong>CNS prophylaxis<\/strong>&nbsp;is mandatory<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-8\"><\/span>Forecast<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>5-year survival rate<\/strong><br>\u2013 at&nbsp;<strong>70\u201380 %<\/strong>&nbsp;(GCB subtype)<br>- <strong>40\u201350 %<\/strong>&nbsp;(ABC subtype)<br><strong>Double-Expresser Phenotype (MYC+BCL2)<\/strong>&nbsp;is an unfavorable factor.&nbsp;<\/li>\n\n\n\n<li><strong>Burkitt's lymphoma<\/strong><br>With&nbsp;<strong>intensive therapy<\/strong>&nbsp;is reached&nbsp;<strong>Healing rates of up to 80-90 %<\/strong>, despite an aggressive course.&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>Extranodal lymphomas<\/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>Hepatosplenic lymphoma<\/strong> (HSTL)<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Hepatosplenic T-cell lymphoma (HSTL)<\/strong>&nbsp;is a rare, aggressive form of peripheral T-cell lymphoma (PTCL) characterized by pronounced involvement of the liver and spleen.  It usually occurs in adulthood and shows a typical clinical triad of&nbsp;<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Hepatosplenomegaly<\/strong><\/li>\n\n\n\n<li><strong>Cytopenias<\/strong><\/li>\n\n\n\n<li><strong>persistent fever<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The diagnosis requires differentiation from other diseases with similar clinical and laboratory findings.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_Merkmale-8\"><\/span>Clinical features<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Clinical picture<\/strong><br>HSTL presents itself with&nbsp;<strong>Acute, severe course<\/strong>, often with fever, weight loss, hepatosplenomegaly and multi-organ involvement (e.g. liver dysfunction, haemorrhagic diathesis)<\/li>\n\n\n\n<li><strong>Cytomorphology<\/strong><br>The lymphoma cells are&nbsp;<strong>small to medium-sized<\/strong>, with irregular nuclei and little cytoplasm.  They show diffuse infiltration in the bone marrow or spleen<\/li>\n\n\n\n<li><strong>Immunophenotype<\/strong><br>The cells express&nbsp;<strong>pan-T-cell antigens (CD2, CD3, CD5, CD7)<\/strong>&nbsp;and are&nbsp;<strong>CD4+ or CD8+<\/strong>, often with&nbsp;<strong>double positivity (CD4+\/CD8+)<\/strong>.  A loss of T-cell antigens can occur. The detection of a&nbsp;<strong>Clonality<\/strong>&nbsp;through T-cell receptor gene rearrangements (TZR) is helpful<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-10\"><\/span>Differential diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Primary hemophagocytic lymphohistiocytosis (HLH)<\/strong><br>Fever, hepatosplenomegaly, cytopenias and hyperferritinemia are also found here.&nbsp;<strong>Hemophagocytosis in the bone marrow is characteristic of HLH<\/strong>, but not specific.  This is usually missing in HSTL. The&nbsp;<strong>Diagnostic criteria for HLH (e.g. 5 of 8 criteria)<\/strong>&nbsp;must be fulfilled in order to exclude HLH.&nbsp;<\/li>\n\n\n\n<li><strong>Infectious systemic diseases<\/strong><br>Sepsis, viral infections (e.g. EBV, HIV), tuberculosis or other infections can cause similar symptoms.&nbsp;<strong>EBV-PCR and EBER-ISH<\/strong>&nbsp;are important for differentiation, as HSTL is not EBV-associated.&nbsp;<\/li>\n\n\n\n<li><strong>Other lymphomas with liver and spleen involvement<\/strong>:\n<ul class=\"wp-block-list\">\n<li><strong>Diffuse large B-cell lymphoma (DLBCL)<\/strong><br>mostly CD20+, CD10+, BCL6+ <br>Usually no CD4+\/CD8+ phenotype<\/li>\n\n\n\n<li><strong>Nodal T-follicular helper cell lymphomas (nTFH lymphomas)<\/strong><br>similar clinical involvement, but with&nbsp;<strong>CD10+, BCL6+, PD1+, CXCL13+<\/strong>&nbsp;and&nbsp;<strong>CD4+<\/strong>&nbsp;Phenotype<br>In contrast to HSTL, nTFH lymphoma is often&nbsp;<strong>CD8-<\/strong><\/li>\n\n\n\n<li><strong>Anaplastic large cell lymphoma (ALCL)<\/strong><br>Can be CD30+, often with ALK-positive or ALK-negative course<br>Less liver and spleen involvement<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Hemophagocytic syndromes in autoimmune diseases<\/strong><br>In the case of Systemic Lupus Erythematosus (SLE) or Juvenile Rheumatoid Arthritis (JRA), a&nbsp;<strong>Macrophage activation syndrome (MAS)<\/strong>&nbsp;differentiated by clinical and laboratory criteria.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methoden-8\"><\/span>Diagnostic methods<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cytomorphology and immunophenotyping<\/strong><br>Mandatory for identification of the T-cell phenotype<\/li>\n\n\n\n<li><strong>FISH and molecular genetics<\/strong><br>Detection of TZR rearrangements<br>Mutations in&nbsp;<strong>TP53<\/strong>,&nbsp;<strong>NOTCH2<\/strong>,&nbsp;<strong>KLF2<\/strong><\/li>\n\n\n\n<li><strong>EBER-ISH<\/strong><br>to exclude EBV-associated lymphomas (e.g. NK\/T-cell lymphoma)&nbsp;<\/li>\n\n\n\n<li><strong>Biopsy<\/strong><br>Bone marrow, spleen or lymph nodes<br>to confirm infiltration and hemophagocytosis if present<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie_und_Prognose-5\"><\/span>Therapy and prognosis<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Therapy<\/strong><br>HSTL is usually associated with&nbsp;<strong>immunochemotherapeutic protocols<\/strong>&nbsp;treated, e.g.&nbsp;&nbsp;<strong>CHOP<\/strong>&nbsp;or&nbsp;<strong>EPOCH<\/strong>.<br>In relapsing or refractory cases, the following are used&nbsp;<strong>Stem cell transplants<\/strong>&nbsp;under consideration<\/li>\n\n\n\n<li><strong>Forecast<\/strong><br><strong>Aggressive course<\/strong>, median survival less than 2 years with inadequate therapy, worse than many other PTCL subtypes<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The differential diagnosis of HSTL is crucial, as treatment and prognosis depend on the exact entity. Close collaboration between hematologists, pathologists and immunologists is necessary.<\/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>Intravascular large B-cell lymphoma<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Intravascular large B-cell lymphoma (IVBZL)<\/strong>&nbsp;is a rare, aggressive form of diffuse large B-cell lymphoma (DLBCL), characterized by a&nbsp;<strong>pure intravascular proliferation of malignant B lymphocytes<\/strong>&nbsp;in small and medium-sized blood vessels of various organs, without significant lymph node infiltration or circulating tumor cells.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_Merkmale-9\"><\/span>Clinical features<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Skin manifestations<\/strong><br>Frequent, blurred, reticular or homogeneous erythema, indurated plaques, subcutaneous nodules (sometimes panniculitic), telangiectasia or petechial foci<br>Skin changes are often asymptomatic, but can be painful<\/li>\n\n\n\n<li><strong>Systemic symptoms (B symptoms)<\/strong><br>Fever, night sweats, weight loss, fatigue - occur in the majority of patients, especially those of Asian origin or with advanced disease<\/li>\n\n\n\n<li><strong>CNS involvement<\/strong><br>Common in Caucasian patients: subacute encephalopathies, epileptic seizures, neurological deficits, cerebral infarctions, myelopathies, peripheral neuropathies<\/li>\n\n\n\n<li><strong>Organ infestation<\/strong><br>Bone marrow, spleen, liver (especially in people of Asian descent), lungs, heart - leads to organ-related symptoms (e.g. shortness of breath, heart failure)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostik\"><\/span>Diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Histology<\/strong><br><strong>Strictly intravascular, pleomorphic, highly pleomorphic B-cell lymphocytes<\/strong>&nbsp;with round\/oval, chromatin-tight cores<br>Vessels are dilated, often with thrombi and fibrinous deposits<\/li>\n\n\n\n<li><strong>Immunohistochemistry<\/strong><br>Positive for&nbsp;<strong>CD20, CD79a, CD19<\/strong>, high proliferation rate (Ki-67: 70-80 %).&nbsp;&nbsp;<strong>Negative for endothelial markers<\/strong>&nbsp;(e.g. CD31, CD34)<br>No clonal T-cell or NK-cell expression<\/li>\n\n\n\n<li><strong>Laboratory<\/strong><br>Frequent anemia (80-90 %), increased LDH, increased beta-2-microglobulin, thrombocytopenia (65 %), leukopenia (25 %), increased erythrocyte sedimentation rate (43 %). Liver, kidney and thyroid values pathological at 15-20 %.&nbsp;<\/li>\n\n\n\n<li><strong>Imaging<\/strong><br>MRI shows non-specific lesions (e.g. multiple cerebral infarcts), which are often misinterpreted<br>PET-CT can be helpful, but no specificity<\/li>\n\n\n\n<li><strong>Histological confirmation by tissue biopsy<\/strong>&nbsp;of an affected organ (e.g. skin, brain, bone marrow)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-11\"><\/span>Differential diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cutaneous B-cell lymphomas<\/strong>&nbsp;(e.g. primary large B-cell lymphoma of the skin)<\/li>\n\n\n\n<li><strong>Reactive angioendotheliomatosis<\/strong>&nbsp;(benign, non-clonal proliferation)<\/li>\n\n\n\n<li><strong>Intravascular T-cell lymphoma<\/strong>&nbsp;(rare, similar morphology, but T-cell phenotype)<\/li>\n\n\n\n<li><strong>Primary effusion lymphoma<\/strong><\/li>\n\n\n\n<li><strong>Kaposi's sarcoma<\/strong><\/li>\n\n\n\n<li><strong>Vasculitides<\/strong>&nbsp;(e.g. polyarteritis nodosa)<\/li>\n\n\n\n<li><strong>Thrombotic microangiopathies<\/strong>&nbsp;(e.g. 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>Therapy and prognosis<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Standard therapy<\/strong><br><strong>R-CHOP protocol<\/strong>&nbsp;(rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone), often 6 cycles<\/li>\n\n\n\n<li><strong>Additive therapies<\/strong><br>With CNS involvement:&nbsp;<strong>CNS prophylaxis<\/strong>&nbsp;(e.g. methotrexate intrathecal), possibly&nbsp;<strong>Rituximab intensive therapy<\/strong>&nbsp;or&nbsp;<strong>Autologous stem cell transplantation<\/strong>&nbsp;on response<\/li>\n\n\n\n<li><strong>Forecast<\/strong><br><strong>Unfavorable<\/strong>, especially in the case of CNS or multi-organ infestation<br>Early diagnosis and treatment improve the survival rate<br>The 5-year survival rate is around 30-50 %, depending on the severity of the infection and response to treatment<\/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>Notice<\/strong>The disease is extremely rare and often difficult to diagnose. The differential diagnosis must be made carefully, as the clinical and radiological findings are non-specific. A&nbsp;<strong>multidisciplinary team<\/strong>&nbsp;(dermatology, hematology, neurology, pathology) is crucial for a correct diagnosis and therapy.<\/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>Primary effusion lymphoma (PEL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Primary effusion lymphoma (PEL)<\/strong>&nbsp;is a rare, aggressive type of B-cell lymphoma that typically manifests as lymphomatous effusions in body cavities (pleura, peritoneum, pericardium) without forming a recognizable tumorous mass.<br>It is&nbsp;<strong>invariable with human herpesvirus 8 (HHV-8, also KSHV)<\/strong>&nbsp;and occurs almost exclusively in immunocompromised patients, especially in HIV-positive people with advanced AIDS.<br>The disease shows a&nbsp;<strong>Plasmablastic differentiation<\/strong>&nbsp;with expression of markers such as CD38, CD138, MUM1\/IRF4 and LANA-1 (latent-associated nuclear antigen-1), but lacking expression of pan-B-cell markers such as CD19, CD20 and CD79a.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-12\"><\/span>Differential diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Diffuse large B-cell lymphoma (DLBCL)<\/strong><br>May also be associated with effusions, but differs by the lack of HHV-8 association and the expression of B-cell markers<br>DLBCL often shows c-myc gene rearrangements that are absent in PEL<\/li>\n\n\n\n<li><strong>Burkitt's lymphoma<\/strong><br>Can rarely occur with effusions, but is characterized by a&nbsp;<strong>MYC rearrangement<\/strong>&nbsp;and typically shows a small-cell, homogeneous cytomorphology.<br>MYC rearrangement is common in HHV-8-negative PEL cases with Burkitt-like morphology<\/li>\n\n\n\n<li><strong>Anaplastic large cell lymphoma (ALCL)<\/strong><br>May be associated with effusions, but is characterized by the expression of CD30 and ALK (in ALK-positive ALCL)<br>PEL is typically ALK-negative and shows plasmablastic differentiation<\/li>\n\n\n\n<li><strong>Pyothorax-associated lymphoma (BAL)<\/strong><br>Develops in chronic pleural periods, usually in patients with pre-existing inflammation<br>It is&nbsp;<strong>not associated with HHV-8<\/strong>, often shows B-cell phenotyping and occurs in a different clinical context<\/li>\n\n\n\n<li><strong>HHV-8-negative, PEL-like lymphomas (type II PEL)<\/strong><br>A rare subgroup without HHV-8 infection that occurs in older, immunocompetent patients with underlying diseases (e.g. liver cirrhosis, kidney failure, heart failure)<br>These cases show a&nbsp;<strong>B-cell phenotyping<\/strong>&nbsp;(CD19, CD20 positive),&nbsp;<strong>Frequent MYC rearrangements<\/strong>&nbsp;and a&nbsp;<strong>Better prognosis<\/strong>&nbsp;as classic PEL<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_und_immunophanotypische_Unterscheidung\"><\/span>Clinical and immunophenotypic differentiation<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\">Feature<\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Classic PEL (Type I)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>HHV-8-negative PEL-like lymphomas (type 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>Positive<\/strong>&nbsp;(obligatory)<\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Negative<\/strong><\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>HIV status<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Mostly positive (advanced AIDS)<\/td><td class=\"has-text-align-left\" data-align=\"left\">Mostly negative, older patients<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Immunosuppression<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Strongly pronounced<\/td><td class=\"has-text-align-left\" data-align=\"left\">Rare, often due to age-related weakness (immunosenescence)<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Cell morphology<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Plasmablastic, immunoblastic<\/td><td class=\"has-text-align-left\" data-align=\"left\">Plasmablastic, immunoblastic,&nbsp;<strong>also Burkitt-like<\/strong><\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>B-cell marker<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Negative<\/strong>&nbsp;(CD19, CD20, CD79a)<\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Positive<\/strong>&nbsp;(CD19, CD20, CD79a)<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Plasma cell markers<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Positive<\/strong>&nbsp;(CD38, CD138, MUM1)<\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Negative<\/strong><\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>MYC rearrangement<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Rare (3%)<\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Frequent (29%)<\/strong><\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>EBV association<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">High (65-80%)<\/td><td class=\"has-text-align-left\" data-align=\"left\">Low (13-30%)<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Forecast<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Very poor (median survival &lt;6 months)<\/td><td class=\"has-text-align-left\" data-align=\"left\">Better (1-year survival rate 47%)<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>Diagnosis<\/strong>&nbsp;from PEL sets the&nbsp;<strong>Detectability of HHV-8 (via LANA-1 immunohistochemistry)<\/strong>&nbsp;ahead.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">If HHV-8-negative effusion lymphomas are suspected, a differentiated analysis of cytomorphology, immunophenotyping, genotyping (MYC, BCL2, BCL6) and clinical background is crucial.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A multidisciplinary approach combining cytology, flow cytometry, molecular biology and immunohistochemistry methods is necessary to correctly differentiate PEL and its differential diagnoses.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"PEL\"><span class=\"ez-toc-section\" id=\"HHV8-Assoziiiertes_Lymphom\"><\/span><strong>HHV8-associated lymphoma<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>HHV-8-associated lymphoma<\/strong>&nbsp;is a rare neoplasia caused by the human herpesvirus 8 (HHV-8), which mainly occurs in HIV-infected patients.  It belongs to a group of lymphoproliferative diseases associated with HHV-8, including the&nbsp;<strong>primary effusion lymphoma (PEL)<\/strong>which&nbsp;<strong>multicentric Castleman's disease (MCD)<\/strong>&nbsp;and that&nbsp;<strong>MCD-associated plasmoblastic lymphoma<\/strong>.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-13\"><\/span>Differential diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The differential presentation of HHV-8-associated lymphoma includes the following diseases:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Primary effusion lymphoma (PEL)<\/strong><br>Characterized by fluid-filled cavities (pleural, peritoneal or pericardial effusions) with plasmablastic cells that are HHV-8-positive and EBV-positive<br>It usually occurs in HIV-positive patients and shows no typical lymph node involvement<\/li>\n\n\n\n<li><strong>Multicentric Castleman's disease (MCD)<\/strong><br>A systemic disease with multiple lymph node enlargement, accompanied by fever, weight loss, hepato- and splenomegaly and elevated cytokines such as IL-6<br>In HHV-8-associated MCD, the virus is detectable in the plasma cells and there is a close association with HIV infection<\/li>\n\n\n\n<li><strong>MCD-associated plasmoblastic lymphoma<\/strong><br>A highly malignant, plasmablastic lymphoma that often occurs in the liver, abdomen or lymph nodes<br>It shows HHV-8 positivity in the tumor cells and may be related to a 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>Clinical and histological features<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cytology<\/strong><br>Plasmablasts with large, irregular nuclei, prominent nucleoli and basophilic cytoplasmata<\/li>\n\n\n\n<li><strong>Immunohistochemistry<\/strong><br>Positive for CD45, CD79a, CD138, MUM1, \u03bb or \u03ba chains, but negative for CD20 and CD30<\/li>\n\n\n\n<li><strong>Virus detection<\/strong><br>HHV-8 by in situ hybridization (EBER) and detection of the viral interleukin (vIL-6) in tumor cells<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_zu_anderen_Lymphomen\"><\/span>Differential diagnosis to other lymphomas<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Non-Hodgkin's lymphoma (NHL)<\/strong><br>Especially plasmablastic lymphomas without HHV-8 association<\/li>\n\n\n\n<li><strong>Kaposi's sarcoma<\/strong><br>Also HHV-8-associated, but histologically characterized by spindle cells and vascular proliferation<\/li>\n\n\n\n<li><strong>Reactive lymphadenopathies<\/strong><br>In infectious or autoimmune diseases, which can also cause lymph node enlargement and cytokine release<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Differential diagnosis requires a combination of clinical findings, histological analysis and molecular biological detection of 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>T-cell and NK-cell lymphomas<\/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>Peripheral T-cell lymphoma (PTCL-NOS)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Peripheral T-cell lymphomas (PTCL-NOS)<\/strong>&nbsp;are a heterogeneous group of rare, mostly aggressive T-cell lymphomas that arise from the umbrella term \u201ePTCL\u201c when no specific subtyping is possible.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The diagnosis of PTCL-NOS requires a&nbsp;<strong>multimodal diagnostics<\/strong>&nbsp;(Histology, IHC, Gene analysis). The differential diagnosis is complex, especially against AITL and ALCL.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The prognosis is poor, but survival varies significantly by molecular subgroup. Therapy should be administered whenever possible in&nbsp;<strong>clinical studies<\/strong>&nbsp;take place.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisch-morphologische_Merkmale-6\"><\/span>Clinical-morphological features<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Clinical symptoms<\/strong><br>Common manifestations include&nbsp;<strong>painless lymph node enlargement<\/strong>,&nbsp;<strong>B symptoms<\/strong>&nbsp;(fever, night sweats, weight loss),&nbsp;<strong>Hepatosplenomegaly<\/strong>&nbsp;and extranodal lesions (e.g., skin, gastrointestinal tract).<br>One&nbsp;<strong>polyclonal hypergammaglobulinemia<\/strong>&nbsp;or&nbsp;<strong>Coombs-positive hemolytic anemia<\/strong>&nbsp;can occur in AITL-like courses.&nbsp;<\/li>\n\n\n\n<li><strong>Morphology<\/strong><br>Histologically, PTCL-NOS show variable architecture:<br>- <strong>Pattern 1<\/strong>&nbsp;(partial paracortical infiltration around hyperplastic germinal centers)<br>- <strong>Pattern 2<\/strong>&nbsp;(extensive paracortical infiltration around regressive germinal centers)<br>- <strong>Pattern 3<\/strong>&nbsp;(completely abrogated architecture). An epithelioid cell-rich, histiocyte-rich infiltration requires differential diagnosis against granulomatous disease or Lennert's lymphoma.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-14\"><\/span>Differential diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>Differential diagnosis from other lymphomas<\/strong>&nbsp;is crucial:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Angioimmunoblastic T-cell lymphoma (AITL)<\/strong><br>PTCL-NOS can be AITL-like. Differentiation by&nbsp;<strong>immunohistochemical markers<\/strong>&nbsp;(CD10, PD-1, BCL6, CXCL13) and&nbsp;<strong>Gene expression analysis<\/strong><br>AITL typically shows strong expression of TFH markers and clonal T-cell receptor gene rearrangement<\/li>\n\n\n\n<li><strong>ALK-negative large cell anaplastic lymphoma (ALCL)<\/strong><br>Characterized by&nbsp;<strong>strong, uniform CD30 expression<\/strong>,&nbsp;<strong>cytotoxic immunophenotype<\/strong>&nbsp;(CD8+, granzyme B+, TIA-1+) and&nbsp;<strong>T-cell receptor gene rearrangement<\/strong><br>The&nbsp;<strong>t(2;5)(p23;q35)<\/strong>Translocation with an NPM-ALK fusion gene is typical in ALCL, not in PTCL-NOS<\/li>\n\n\n\n<li><strong>Reactive lymph node changes<\/strong><br>Kikuchi's lymphadenitis (speckled necrosis, lack of clonality) or chronic inflammation can mimic PTCL-NOS<br><strong>Clonality detection<\/strong>&nbsp;(TCR gene rearrangement PCR) is crucial<\/li>\n\n\n\n<li><strong>Nodal peripheral T-cell lymphomas with T-follicular helper phenotype<\/strong><br>A newly defined entity (WHO 2017) that previously belonged to PTCL-NOS<br>She has a&nbsp;<strong>CD4+\/BCL6+\/PD-1+<\/strong>-Expression and Mutations in&nbsp;<strong>TET2, IDH2, DNMT3A<\/strong>&nbsp;on.<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methoden-9\"><\/span>Diagnostic methods<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Immunohistochemistry (IHC)<\/strong><br>\u2013 Key markers are&nbsp;<strong>CD3, CD4, CD5, CD2, CD7<\/strong>&nbsp;(often reduced).<br>- <strong>CD30 Expression<\/strong>&nbsp;is&nbsp;<strong>heterogeneous<\/strong>&nbsp;(CD30+ vs. CD30\u2212), where CD30+ shows a better prognosis and similarity to ALCL<\/li>\n\n\n\n<li><strong>Gene expression analysis<\/strong><br>Distinction into two main groups:<br>- <strong>GATA3 group<\/strong>&nbsp;low 5-year survival:&nbsp;<strong>19 %<\/strong>)<br>- <strong>TBX21 group<\/strong>&nbsp;higher 5-year survival:&nbsp;<strong>38 %<\/strong>)<\/li>\n\n\n\n<li><strong>Molecular genetics<\/strong><br>- <strong>Mutations in epigenetic regulators<\/strong>&nbsp;(TET2, DNMT3A, IDH2, MLL2, KDM6A) in ca. 25 %<br>- <strong>t(5;9)(q33;q22)<\/strong>&nbsp;with ITK\/SYK fusion gene (approx. 10 %)<br>- <strong>VAV1 fusion products<\/strong>&nbsp;(11 %)<\/li>\n\n\n\n<li><strong>Microarray technology<\/strong><br>Differentiation of AITL, ALCL, and PTCL-NOS with up to 98 % accuracy<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-10\"><\/span>Therapy<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Primary therapy<\/strong><br>- <strong>CHOP or CHOP-like anthracycline-based chemotherapy<\/strong>&nbsp;is standard.<br><strong>Brentuximab Vedotin<\/strong>&nbsp;(anti-CD30) is used in CD30+ PTCL-NOS, and response has also been observed in CD30-negative cases<\/li>\n\n\n\n<li><strong>Consolidation<\/strong><br>With good response to induction therapy<br><strong>autologous stem cell transplantation (auto-SCT)<\/strong><\/li>\n\n\n\n<li><strong>Recurrent\/refractory<\/strong><br><strong>Allogeneic stem cell transplantation (allo-SCT)<\/strong>,&nbsp;<strong>Romidepsin<\/strong>,&nbsp;<strong>Belinostat<\/strong>,&nbsp;<strong>Pralatrexate<\/strong><\/li>\n\n\n\n<li><strong>Targeted therapies<\/strong><br>\u2013 Hypomethylating agents (e.g., azacitidine) in TET2 mutations<br>- <strong>JAK\/STAT inhibitors<\/strong>&nbsp;in STAT3-activating mutations<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-9\"><\/span>Forecast<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Median overall survival<\/strong><br><strong>10.5 months<\/strong>&nbsp;for PTL-NOS-CD30\u2212<br><strong>19-38 % 5-year survival rate<\/strong>&nbsp;depending on the gene signature (GATA3 vs. TBX21)<\/li>\n\n\n\n<li><strong>Prognostic factors<\/strong><br><strong>CD30 Expression<\/strong>,&nbsp;<strong>Transcription factor signature (GATA3\/TBX21)<\/strong>,&nbsp;<strong>Age group<\/strong>,&nbsp;<strong>Disease stage<\/strong>,&nbsp;<strong>Recurrence status<\/strong><\/li>\n\n\n\n<li><strong>Therapy claim<\/strong><br>Primarily curative, but&nbsp;<strong>no therapeutic breakthrough<\/strong>&nbsp;for years.<br><strong>Clinical studies<\/strong>&nbsp;are recommended.<\/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>Angioimmunoblastic T-cell lymphoma (AITL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The <strong>Angioimmunoblastic T-cell lymphoma (AITL)<\/strong>&nbsp;is a rare, aggressive peripheral T-cell lymphoma that originates from&nbsp;<strong>follicular T helper cells (TFH)<\/strong>&nbsp;goes out and about&nbsp;<strong>1\u20132 % of Non-Hodgkin lymphoma<\/strong>&nbsp;It primarily affects older patients in their 6th to 7th decade of life and is characterized by a complex, often unspecific clinical presentation.&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>Clinical features and morphological signs<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Common Symptoms<\/strong><br>- <strong>B symptoms<\/strong>Fever, night sweats, weight loss, fatigue<br>- <strong>Generalized lymphadenopathy<\/strong>&nbsp;(Neck, armpit, groin)<br>- <strong>Hepatosplenomegaly<\/strong><br>- <strong>Anemia<\/strong>,&nbsp;<strong>Thrombocytopenia<\/strong>,&nbsp;<strong>Lymphopenia<\/strong><br>- <strong>Polyclonal hypergammaglobulinemia<\/strong>&nbsp;and&nbsp;<strong>Hypereosinophilia<\/strong>&nbsp;(in 30-40 %)<br>- <strong>Payment<\/strong>&nbsp;(e.g., facial edema, ascites, pulmonary edema)<br>- <strong>Arthralgia<\/strong>,&nbsp;<strong>Susceptibility to infection<\/strong>,&nbsp;<strong>neurological disorders<\/strong>&nbsp;(e.g., polyneuropathy)<\/li>\n\n\n\n<li><strong>Skin manifestations<\/strong>&nbsp;(in up to 50 % of patients)<br>- <strong>Maculopapular rash<\/strong>&nbsp;(frequent first symptoms)<br>- <strong>itching<\/strong>&nbsp;Itching<br>- <strong>Macular and nodular rash<\/strong>&nbsp;with \u201edeck chair sign\u201c (excision of skin folds)<br>- <strong>Nodular or plaque-like lesions<\/strong>, which to&nbsp;<strong>Mycosis fungoides<\/strong>&nbsp;can remember<br>- <strong>Rare<\/strong>Association with&nbsp;<strong>Linear IgA dermatosis<\/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>Differential diagnosis<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The AITL is often mistakenly referred to as&nbsp;<strong>infectious or drug-induced disease<\/strong>&nbsp;diagnosed, as the symptoms heavily overlap:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms)<\/strong><br>\u2013 Similar symptoms: fever, rash, lymphadenopathy, eosinophilia, hypergammaglobulinemia<br>\u2013 Distinction by&nbsp;<strong>Medical History (Medication Use)<\/strong>,&nbsp;<strong>Negative EBV detection in serum<\/strong>,&nbsp;<strong>missing clonal T cell proliferation<\/strong><br>- <strong>AITL: EBV-positive, clonal T-cell genome alteration<\/strong><\/li>\n\n\n\n<li><strong>Infectious diseases<\/strong><br>- <strong>Viruses<\/strong> \u2013 EBV, HIV, HCV, HHV-6, Hantaviruses<br>- <strong>bacteria<\/strong> -&nbsp;<em>Klebsiella pneumoniae<\/em>,&nbsp;<em>Mycoplasma<\/em>,&nbsp;<em>Borrelia<\/em><br>- <strong>Parasites<\/strong> Leishmania<br>- <strong>Differential - PCR, serology, blood cultures, clinical context analysis<\/strong>&nbsp;<\/li>\n\n\n\n<li><strong>Other lymphomas<\/strong><br>- <strong>Peripheral T-cell lymphomas, NOS<\/strong>&nbsp;(not otherwise classified)<br>- <strong>Mycosis fungoides<\/strong>&nbsp;(continuous skin infiltration, CD4+\/CD8- phenotype)<br>- <strong>Classical Hodgkin's lymphoma<\/strong>&nbsp;Reed-Sternberg cells, CD15+\/CD30+<br>- <strong>Lennert's Lymphoma<\/strong>&nbsp;(Epithelioid cell infiltrate, strong histiocytic pattern)&nbsp;<\/li>\n\n\n\n<li><strong>Autoimmune diseases<\/strong><br>- <strong>Stiff-person syndrome<\/strong>,&nbsp;<strong>SLE<\/strong>,&nbsp;<strong>Sj\u00f6gren's Syndrome<\/strong><br>- <strong>Differential \u2013 Autoantibodies (ANA, ENA), clinical criteria<\/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>Diagnostic Methodology<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ol start=\"1\" class=\"wp-block-list\">\n<li><strong>Clinical examination<\/strong><br>\u2013 Palpation of lymph nodes, liver, spleen<br>\u2013 Assessment of skin lesions, edema, enanthems&nbsp;<\/li>\n\n\n\n<li><strong>Laboratory tests<\/strong><br>- <strong>Blood count<\/strong> Anemia, thrombocytopenia, lymphopenia, hypereosinophilia<br>- <strong>Inflammation markers<\/strong> \u2013 CRP increased, ESR increased<br>- <strong>Functional testing<\/strong> \u2013 LDH \u2191, Beta-2-Microglobulin \u2191<br>- <strong>Electrophoresis<\/strong> Hypergammaglobulinemia<br>- <strong>PCR<\/strong> \u2013 EBV-DNA in serum (positive in 80\u201390 % of cases)<\/li>\n\n\n\n<li><strong>Imaging<\/strong><br>- <strong>Ultrasound\/CT\/MRI<\/strong>Enlarged lymph nodes (multiloculated), hepato-\/splenomegaly, ascites<\/li>\n\n\n\n<li><strong>Biopsy<\/strong><br>- <strong>Lymph node biopsy<\/strong>&nbsp;(not peripheral blood or bone marrow biopsy)<br>- <strong>Pathohistology<\/strong><br>\u2013 Disrupted architecture, polymorphous infiltrate of lymphocytes, histiocytes, eosinophils, plasma cells<br>\u2013 \u2013 <strong>Proliferated, branched venules<\/strong><br>\u2013 \u2013 <strong>Perivascular and paracortical infiltrates<\/strong><br>\u2013 \u2013 <strong>EBV-positive B-immunoblasts<\/strong>&nbsp;(not in T-cells)<br>\u2013 \u2013 <strong>Reed-Sternberg-like cells<\/strong>&nbsp;possible<\/li>\n\n\n\n<li><strong>Immunohistochemistry<\/strong><br>- <strong>Positive<\/strong> \u2013 CD3, CD4, CD5, CD10, PD-1, ICOS, BCL6, CXCL13, CD20 (in B cells)<br>- <strong>Negative<\/strong>CD8, CD30 (not in typical Hodgkin cells)<br>- <strong>CXCL13 and CD10<\/strong> \u2013 highest specificity for AITL&nbsp;<\/li>\n\n\n\n<li><strong>Flow cytometry<\/strong><br>- <strong>sCD3\u2013\/CD4+<\/strong>&nbsp;T cells in peripheral blood: high positive predictive value&nbsp;<\/li>\n\n\n\n<li><strong>Molecular biology<\/strong><br>- <strong>Clonal T-cell receptor gene arrangement<\/strong>&nbsp;(70\u201390 %)<br>- <strong>Mutations<\/strong>:&nbsp;<em>RHOA<\/em>&nbsp;(G17V),&nbsp;<em>TET2<\/em>,&nbsp;<em>IDH2<\/em>,&nbsp;<em>DNMT3A<\/em><br>- <strong>CTLA4-\/CD28-Fusion<\/strong>&nbsp;in 50 % der F\u00e4lle&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>Therapy<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>First line<\/strong><br>- <strong>Anthracycline-based chemotherapy<\/strong><br>\u2013 \u2013 <strong>CHOP<\/strong>&nbsp;(Cyclophosphamide, Doxorubicin, Vincristine, Prednisone)<br>\u2013 \u2013 <strong>R-CHOP<\/strong>&nbsp;(with Rituximab)<br>\u2013 \u2013 <strong>CHOP<\/strong>&nbsp;(with Etoposide)<br>\u2013 \u2013 <strong>Addition of Pegfilgrastim<\/strong>&nbsp;for granulocyte prophylaxis<\/li>\n\n\n\n<li><strong>Second-line \u2013 High-risk \/ Relapsed<\/strong><br>- <strong>Stem cell transplantation<\/strong>&nbsp;(autologous or allogeneic) after remission<br>- <strong>New Drugs in Clinical Trials<\/strong><br>\u2013 \u2013 <strong>Brentuximab vedotin<\/strong>&nbsp;(CD30-targeted)<br>\u2013 \u2013 <strong>Brentuximab vedotin<\/strong>&nbsp;(CD30-targeted)<br>\u2013 \u2013 <strong>Lenalidomide<\/strong>&nbsp;(immunomodulatory)<\/li>\n\n\n\n<li><strong>Palliative therapy for insufficient response<\/strong><br>- <strong>Glucocorticoids<\/strong>&nbsp;Prednisone 80\u2013100 mg\/day, decreasing<br>- <strong>Cytostatics<\/strong>Chlorambucil, Cyclophosphamide<br>- <strong>Immunomodulators<\/strong>Cyclosporine<\/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>Forecast<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The forecast of&nbsp;<strong>Angioimmunoblastic T-cell lymphoma (AITL)<\/strong>&nbsp;is overall&nbsp;<strong>unfavorable<\/strong>, with a&nbsp;<strong>5-year survival rate of about 30-32 %<\/strong>&nbsp;and one&nbsp;<strong>Median survival time of 18\u201329 months<\/strong>.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Several prognostic scores are used for risk stratification:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>International Prognostic Index (IPI)<\/strong><br>Unfavorable factors:<br>\u2013 Over 60 years old<br>\u2013 ECOG Performance Status \u2265 2<br>\u2013 Elevated LDH<br>\u2013 Ann-Arbor-Stadium \u2265 III<br>1 extranodal spread<\/li>\n\n\n\n<li><strong>Prognostic Index for T-cell Lymphoma (PIT)<\/strong><br>Taking into account:<br>\u2013 Over 60 years old<br>\u2013 ECOG Performance Status \u2265 2<br>\u2013 Elevated LDH<br>- <strong>Bone marrow involvement<\/strong><\/li>\n\n\n\n<li><strong>Modified PIT (mPIT)<\/strong><br>\u2013 Replaces bone marrow infiltration by&nbsp;<strong>Ki-67 Proliferation Index &gt; 75 %<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">When applying the&nbsp;<strong>PIT Scores<\/strong>&nbsp;Here are the 5-year survival rates for PTCL (including AITL):<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Low risk<\/strong>: 75 %<\/li>\n\n\n\n<li><strong>Low-intermediate risk<\/strong>: 30 %<\/li>\n\n\n\n<li><strong>High-intermediate risk<\/strong>: 15 %<\/li>\n\n\n\n<li><strong>High risk<\/strong>: 0 %&nbsp;<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">A&nbsp;<strong>highly unfavorable outcome<\/strong>&nbsp;will be&nbsp;<strong>Stage IVB<\/strong>,&nbsp;<strong>Bone marrow infiltration<\/strong>&nbsp;(as in the case study with 10 %) and&nbsp;<strong>Lack of remission after initial therapy<\/strong>&nbsp;expected.<\/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>Cutaneous T-cell lymphoma<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The <strong>Follicular T-cell lymphoma (FTCL)<\/strong>&nbsp;is the same entity and is also known by these synonyms <strong>PTFCL<\/strong>, <strong>F-PTCL<\/strong>, <strong>nTFHL<\/strong> managed, a very rare, aggressively progressing T-cell lymphoma type that originates from&nbsp;<strong>follicular T helper cells (TFH)<\/strong>&nbsp;derived and listed as a distinct entity in the current WHO classification (2017). Previously assigned to the PTCL-NOS group.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Follicular lymphoma is a tumor with&nbsp;<strong>characteristic TFH phenotype<\/strong>, which through&nbsp;<strong>Differential diagnosis of AITL, Hodgkin lymphoma, and follicular B-cell lymphoma<\/strong>&nbsp;must be delimited.<br>The diagnosis requires&nbsp;<strong>careful histological and immunohistochemical evaluation<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Therapy is&nbsp;<strong>Symptomatic and empirical<\/strong>, Forecast&nbsp;<strong>unfavorable<\/strong>.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisch-morphologische_Merkmale-7\"><\/span>Clinical-morphological features<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Age and gender<\/strong><br>Primarily affected are&nbsp;<strong>Middle-aged to older adults (33\u201388 years)<\/strong>, with a&nbsp;<strong>slight preference for men<\/strong><\/li>\n\n\n\n<li><strong>Clinical presentation<\/strong><br>Resembles the&nbsp;<strong>Angioimmunoblastic T-cell lymphoma (AITL)<\/strong><br>Common symptoms include&nbsp;<strong>generalized lymphadenopathy, splenomegaly, B symptoms (fever, night sweats, weight loss)<\/strong>&nbsp;and&nbsp;<strong>Skin lesions in about one-third of patients<\/strong><br>These are&nbsp;<strong>not typical for MF<\/strong>&nbsp;(no scaly, firm papules\/plaques)<\/li>\n\n\n\n<li><strong>Histology<\/strong><br>The lymph nodes show a&nbsp;<strong>Nodular\/follicular proliferation of medium-sized, monomorphic lymphoid cells<\/strong>&nbsp;with&nbsp;<strong>partial or complete infiltration of the lymph follicles<\/strong><br>The&nbsp;<strong>The mantle zone is reduced or missing.<\/strong><br>In contrast to reactive changes and B-cell lymphomas (e.g., follicular lymphoma), the&nbsp;<strong>Differentiation difficult without immunohistochemistry<\/strong><\/li>\n\n\n\n<li><strong>Immunophenotype<\/strong><br>Neoplastic cells express&nbsp;<strong>T-cell antigens (CD2, CD3, CD5)<\/strong>, are&nbsp;<strong>CD4+<\/strong>,&nbsp;<strong>CD8\u2013<\/strong>, show&nbsp;<strong>CD7 Deficiency<\/strong>&nbsp;and one&nbsp;<strong>characteristic TFH phenotype<\/strong>&nbsp;with expression of&nbsp;<strong>PD-1, CXCL13, BCL6, CD10, and ICOS<\/strong><br><strong>CD20-positive immunoblasts<\/strong>&nbsp;are often&nbsp;<strong>EBV-positive<\/strong>&nbsp;and can even&nbsp;<strong>Hodgkin\/Reed-Sternberg-like cells<\/strong>&nbsp;form<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_-methodik\"><\/span>Differential diagnosis and methodology<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Key differential diagnoses<\/strong><br>- <strong>Angioimmunoblastic T-cell lymphoma (AITL)<\/strong><br>Similar clinical symptoms and TFH phenotype, but FTCL lacks typical AITL features such as&nbsp;<strong>vascular proliferates, FD cells, and inflammatory background<\/strong><br>- <strong>Hodgkin lymphoma (classic)<\/strong><br>EBV-positive, CD30+\/CD15+ cells can exhibit the phenotype of Hodgkin cells. Differentiation by&nbsp;<strong>Immunophenotype and cell morphology<\/strong><br>- <strong>Follicular lymphoma (FL)<\/strong><br>Similar morphological pattern (follicular growth), but FL is a&nbsp;<strong>B-cell lymphoma<\/strong>&nbsp;with&nbsp;<strong>CD20+, CD5\u2013, BCL6+, and BCL2+<\/strong>&nbsp;Cells<br><strong>CD4+ TFH phenotype in FTCL is critical<\/strong><br>- <strong>Marginal zone lymphoma or nodular lymphocyte-predominant Hodgkin lymphoma<\/strong><br>Differentiation through&nbsp;<strong>Immunophenotyping and molecular analyses<\/strong><\/li>\n\n\n\n<li><strong>Diagnostics<\/strong><br>- <strong>Lymph node biopsy<\/strong>&nbsp;with&nbsp;<strong>pronounced histological and immunohistochemical evaluation<\/strong>&nbsp;by an experienced pathologist<br>- <strong>Immunohistochemistry<\/strong> Proof of&nbsp;<strong>CD4, PD-1, CXCL13, BCL6, CD10, ICOS<\/strong>&nbsp;and&nbsp;<strong>Absence of CD7<\/strong><br>- <strong>Molecular biology<\/strong> -&nbsp;<strong>t(5;9)(q33;q22)-Translocation<\/strong>&nbsp;(ITK-SYK-fusion gene) approximately&nbsp;<strong>20 % of the cases<\/strong>.<br>Mutations in&nbsp;<strong>RHOA, TET2, IDH2, DNMT3A<\/strong>&nbsp;are also described<br>- <strong>Clonality analysis<\/strong> \u2013 Demonstration of a clonal T-cell receptor genome<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-12\"><\/span>Therapy<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>No established standard therapy<\/strong>&nbsp;due to low case numbers<\/li>\n\n\n\n<li><strong>First-line therapy<\/strong><br><strong>CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone)<\/strong><br>or&nbsp;<strong>Cheops<\/strong><\/li>\n\n\n\n<li><strong>Second-line therapy<\/strong><br>In appropriate patients&nbsp;<strong>autologous or allogeneic stem cell transplantation<\/strong>.&nbsp;<\/li>\n\n\n\n<li><strong>Clinical studies<\/strong><br>Testing new therapies (e.g.&nbsp;<strong>immunotherapeutic approaches<\/strong>,&nbsp;<strong>Targeted therapies<\/strong>).&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-11\"><\/span>Forecast<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Aggressive clinical course<\/strong>&nbsp;with&nbsp;<strong>poor prognosis<\/strong>.&nbsp;<\/li>\n\n\n\n<li><strong>Approximately 50 % of patients die within the first 24 months after diagnosis.<\/strong>.&nbsp;<\/li>\n\n\n\n<li>The&nbsp;<strong>Survival rate is significantly worse<\/strong>&nbsp;as with most other PTCL subtypes.<\/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>Hepatosplenic T-cell lymphoma (\u03b3\u03b4-type)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Hepatosplenic T-cell lymphoma (HSTCL) is a&nbsp;<strong>very rare, clinically aggressive, systemic T-NHL<\/strong>&nbsp;(&lt;1% of non-Hodgkin lymphomas), which mostly originates from&nbsp;<strong>\u03b3\u03b4 T cells<\/strong>&nbsp;descends.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It is characterized by a&nbsp;<strong>exclusive involvement of spleen, liver, and bone marrow<\/strong>&nbsp;as, where&nbsp;<strong>Lymphadenopathy or leukemic infiltration are usually absent<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The disease occurs primarily in&nbsp;<strong>Adolescent to young adult age<\/strong>&nbsp;at (average age: 38 years), men are significantly more affected. A significant proportion of cases is associated with&nbsp;<strong>chronic immunosuppression<\/strong>&nbsp;associated.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinische_und_klinisch-morphologische_Merkmale\"><\/span><strong>Clinical and clinicomorphological characteristics<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Patients typically present with&nbsp;<strong>B-symptoms (fever, night sweats, weight loss), hepatosplenomegaly, and pancytopenia<\/strong>, that can be reminiscent of acute leukemia.<br>A&nbsp;<strong>Hemophagocytic syndrome<\/strong>&nbsp;also occurs.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Laboratory<\/strong><br>- <strong>elevated lactate dehydrogenase (71.4 %<\/strong><br>- <strong>Liver dysfunction (42.9 %<\/strong><br>- <strong>reduced fibrinogen (35.7 %)<\/strong><\/li>\n\n\n\n<li><strong>Histology<\/strong><br>Morphologically, the lymphoma shows a&nbsp;<strong>Sinusoidal, monomorphic infiltrate of medium-sized cells with pale cytoplasm<\/strong>.<\/li>\n\n\n\n<li><strong>Immunophenotype<\/strong><br>The immune phenotype is characteristic:&nbsp;<strong>CD3+, CD5-, CD8-, CD4-, CD56+, TCR \u03b3\u03b4+, Granzyme B+<\/strong>, mostly&nbsp;<strong>TCR \u03b1\u03b2 negative<\/strong><\/li>\n\n\n\n<li><strong>Molecular biology<\/strong><br>Genetically&nbsp;<strong>Isochromosome 7q and trisomy 8<\/strong>&nbsp;the most common chromosomal aberrations<br>Mutations in&nbsp;<strong>STAT3\/STAT5B (JAK-STAT signaling pathway)<\/strong>&nbsp;and&nbsp;<strong>SETD2, IN080, ARID1 (Chromatin modification)<\/strong>&nbsp;are frequent and potentially therapeutically relevant&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>Differential diagnosis and methodology<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The differential diagnosis includes:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Acute leukemia<\/strong>&nbsp;(especially in pancytopenia and leukocytosis in peripheral blood)&nbsp;<\/li>\n\n\n\n<li><strong>Other T-cell lymphomas<\/strong>&nbsp;(e.g.&nbsp;<strong>T-cell prolymphocytic leukemia (T-PLL)<\/strong>,&nbsp;<strong>Angioimmunoblastic T-cell lymphoma (AITL)<\/strong>,&nbsp;<strong>NK\/T-cell lymphoma<\/strong>)<\/li>\n\n\n\n<li><strong>Hemophagocytic Lymphohistiocytosis<\/strong> can be triggered by infectious, autoimmune, or malignant causes<\/li>\n\n\n\n<li><strong>Other extranodal lymphomas<\/strong>&nbsp;with liver\/spleen involvement<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">For a safe diagnosis,&nbsp;<strong>obligated<\/strong>&nbsp;The following methods are required:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cytomorphology<\/strong>&nbsp;(peripheral blood, bone marrow, spleen biopsy)<\/li>\n\n\n\n<li><strong>Immunophenotyping<\/strong>&nbsp;(Flow cytometry) with detection of the \u03b3\u03b4 T cell phenotype<\/li>\n\n\n\n<li><strong>Chromosome analysis<\/strong>&nbsp;and&nbsp;<strong>FISH<\/strong>&nbsp;for the detection of 7q and trisomy 8<\/li>\n\n\n\n<li><strong>Molecular genetics<\/strong>&nbsp;(PCR for TCR gene rearrangements, sequencing for mutation detection in 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>Therapy<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">There are&nbsp;<strong>no uniform treatment standard<\/strong>. Currently, the&nbsp;<strong>Allogene hematopoietic stem cell transplantation (HSCT)<\/strong> the only approach with proven clinical efficacy and is used in&nbsp;<strong>first-line treated patients with remission<\/strong>&nbsp;Recommended for consolidation.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Chemotherapies (e.g.&nbsp;<strong>CHOP, EPOCH<\/strong>) show limited success, and recurrences are common.&nbsp;&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-12\"><\/span>Forecast<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>The prognosis is poor<\/strong><br>\u2013 The median survival time is under three years<br>the 5-year survival rate is less than 20 %<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>The disease is associated with a high risk of recurrence.<\/strong>&nbsp;and&nbsp;<strong>low therapeutic response<\/strong>&nbsp;connected.&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>Notice<\/strong>The diagnosis requires an interdisciplinary work-up by oncologists, hematologists, and pathologists. Current data is limited as HSTCL is a very rare disease.<\/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>Enteropathy-associated T-cell lymphoma (EATL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>Enteropathy-associated T-cell lymphoma (EATL)<\/strong>&nbsp;is an aggressive non-Hodgkin lymphoma of the gastrointestinal tract that develops from intestinal intraepithelial cytotoxic T-cells.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The current WHO classification (2017) uses the term&nbsp;<strong>EAT<\/strong>&nbsp;exclusively for the&nbsp;<strong>EATL Type 1<\/strong>, associated with gluten-sensitive enteropathy (celiac disease).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>gamma-delta type<\/strong>&nbsp;is a rare but clinically relevant subtype characterized by a $\\gamma\\delta$ T-cell phenotype and requires special attention in the differential diagnosis.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild\"><\/span>Clinical picture<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Most common infestation<\/strong>Small intestine (especially jejunum), mesentery; rarer localizations in the gastrointestinal tract.&nbsp;<\/li>\n\n\n\n<li><strong>Clinical symptoms<\/strong>Abdominal pain (most common symptom), steatorrhea, weight loss, malabsorption, gastrointestinal bleeding, anemia, B symptoms, intestinal obstruction, or intestinal perforation.<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Morphologische_Merkmale\"><\/span><strong>Morphological characteristics<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>EATL Type 1 (Classic)<\/strong>Associated with celiac disease;&nbsp;<strong>CD56-negative<\/strong>,&nbsp;<strong>CD8+<\/strong>,&nbsp;<strong>CD56-negative<\/strong>; clonal T-cell proliferation with cytotoxic morphology<\/li>\n\n\n\n<li><strong>EATL-Type 2 (new nomenclature: Monomorphic epitheliotropic intestinal T-cell lymphoma, MEITL)<\/strong>:&nbsp;<strong>CD56-positive<\/strong>,&nbsp;<strong>no association with celiac disease<\/strong>, more common in older patients, aggressive course<\/li>\n\n\n\n<li><strong>gamma delta T cell subtype<\/strong>Rare, characterized by&nbsp;<strong>Gamma Delta T Cell Receptor Expression<\/strong>,&nbsp;<strong>CD3+<\/strong>,&nbsp;<strong>CD56+<\/strong>,&nbsp;<strong>CD4<\/strong>,&nbsp;<strong>CD8\u2013<\/strong>; often with pronounced epitheliotropism and distinct morphology. The differentiation of&nbsp;<strong>Indolent T-cell lymphoproliferations<\/strong>&nbsp;(e.g., indolent T-cell lymphoproliferative disorder of the gastrointestinal tract) is crucial, as this can&nbsp;<strong>benign, slow-progressing disease<\/strong>&nbsp;with&nbsp;<strong>low proliferation rate (10\u201315%)<\/strong>&nbsp;and&nbsp;<strong>superficial infiltrate<\/strong>&nbsp;represent.<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-15\"><\/span>Differential diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Refractory Celiac Disease (RCD) Type II<\/strong>Clonal intraepithelial T lymphocytes with aberrant phenotype (e.g., CD8\u2013, CD56+, TCR\u03b3\u03b4+), high transformation rate into EATL<\/li>\n\n\n\n<li><strong>Indolent T-cell lymphoproliferations of the gastrointestinal tract<\/strong>Superficial, non-destructive infiltrate, low proliferation rate,&nbsp;<strong>no massive tumorous process<\/strong>,&nbsp;<strong>mixed cytology<\/strong>,&nbsp;<strong>persistent lesions without progression<\/strong><\/li>\n\n\n\n<li><strong>Indolent NK-cell enteropathy\/gastropathy<\/strong>CD3+, CD56+, CD4\u2013, CD8\u2013, atypical medium-sized cells,&nbsp;<strong>no T-cell genre arrangements<\/strong><\/li>\n\n\n\n<li><strong>Extranodal NK\/T-cell lymphomas<\/strong>Associated with Epstein-Barr virus (EBV),&nbsp;<strong>not with celiac disease<\/strong>,&nbsp;<strong>CD56+<\/strong>,&nbsp;<strong>TIA1+<\/strong>,&nbsp;<strong>granzyme B+<\/strong>,&nbsp;<strong>EBV-LMP1+<\/strong><\/li>\n\n\n\n<li><strong>Gastrointestinal lymphomas of other genesis<\/strong>B-cell lymphomas (e.g., diffuse large B-cell lymphoma), follicular lymphoma, marginal zone lymphoma<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methodik-2\"><\/span><strong>Diagnostic Methodology<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Endoscopy with small bowel biopsy<\/strong><br>Macroscopic: multiple ulcers, perforations possible<\/li>\n\n\n\n<li><strong>Histology<\/strong><br>Proof of&nbsp;<strong>T-cell clonality<\/strong>&nbsp;(PCR for TCR genre arrangements),&nbsp;<br><strong>immunohistochemical profiles<\/strong>&nbsp;(CD3, CD4, CD8, CD56, TCR\u03b1\u03b2\/\u03b3\u03b4, CD57, granzyme B)<\/li>\n\n\n\n<li><strong>Molecular biology<\/strong><br>proof&nbsp;<strong>recurrent mutations in the JAK\/STAT signaling pathway<\/strong>&nbsp;(e.g. STAT3, JAK1),<br><strong>chromosomal gains (9q33-q34)<\/strong>.<\/li>\n\n\n\n<li><strong>DUSP22-Rearrangements<\/strong><br>Rare in EATL, can occur in cutaneous CD30+ lymphoproliferations, broaden the differential diagnosis.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-14\"><\/span>Therapy<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Consistent gluten-free diet<\/strong><br><strong>Prophylaxis<\/strong>, can prevent development.&nbsp;<\/li>\n\n\n\n<li><strong>Chemotherapy<\/strong><br><strong>CHOP scheme<\/strong>&nbsp;(Cyclophosphamide, Doxorubicin, Vincristine, Prednisone), possibly with&nbsp;<strong>Etoposide<\/strong>&nbsp;in patients &lt; 60 years old<\/li>\n\n\n\n<li><strong>Autologous stem cell transplantation<\/strong><br>Option for younger patients with relapsed or refractory disease<\/li>\n\n\n\n<li><strong>Corticosteroids<\/strong><br>For refractory celiac disease symptoms<\/li>\n\n\n\n<li><strong>Watch &amp; Wait Strategy<\/strong><br>Only in indolent lymphoproliferative disorders, not in EATL.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-13\"><\/span>Forecast<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Aggressive course<\/strong>, high metastatic rate (liver, spleen, skin)<\/li>\n\n\n\n<li><strong>Bowel perforation<\/strong>&nbsp;as a typical complication<\/li>\n\n\n\n<li><strong>Median survival time from diagnosis<\/strong>&nbsp;<strong>10 months<\/strong><\/li>\n\n\n\n<li><strong>Prognostic factors<\/strong><br>Age, Stadium, clonal T-cell proliferation, mutations in the JAK\/STAT pathway, CD56 status, therapy response.&nbsp;<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Summary<\/strong>The differential diagnosis of&nbsp;<strong>gamma delta T-cell enteropathy-associated T-cell lymphoma<\/strong>&nbsp;requires a close combination of clinical, endoscopic, histological, and molecular biological analysis.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>Exclusion diagnosis of indolent lymphoproliferative disorders<\/strong>&nbsp;is crucial to avoid excessive, harmful chemotherapy.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The therapy is aggressive, the prognosis is poor, early diagnosis and treatment are vital.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Anaplastisches_groszelliges_Lymphom_ALCL\"><\/span><strong>Anaplastic large cell lymphoma (ALCL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The <strong>Anaplastic large cell lymphoma (ALCL)<\/strong>&nbsp;is a rare, aggressive,&nbsp;<strong>CD30-positive Non-Hodgkin Lymphoma<\/strong>, which primarily originates from T-cells and is found frequently in&nbsp;<strong>Childhood and early adulthood<\/strong>&nbsp;performance.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It is divided into two main groups:&nbsp;<strong>ALK-positive (ALK+ ALCL)<\/strong>&nbsp;and&nbsp;<strong>ALK-negative (ALK\u2013 ALCL)<\/strong>, whereby ALK expression causes crucial clinical-pathological and prognostic differences.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild-2\"><\/span>Clinical picture<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Systemic ALCL<\/strong><br>Typically wears&nbsp;<strong>B symptoms<\/strong>&nbsp;(Fever, night sweats, weight loss), mostly in advanced stages (III\/IV)<br>Common extranodal infiltrates affect the skin, liver, lungs, soft tissues, bones, and bone marrow (approx. 15 %).<\/li>\n\n\n\n<li><strong>Primary cutaneous ALCL (cALCL)<\/strong><br>It mostly occurs in older men and presents as&nbsp;<strong>solitary, ulcerated skin tumors<\/strong>&nbsp;with&nbsp;<strong>cheaper forecast<\/strong>&nbsp;(10-year survival rate &gt;90 %)<br>Unlike systemic ALCL, cALCL&nbsp;<strong>ALK-negative<\/strong>&nbsp;and&nbsp;<strong>EMA-negative<\/strong><\/li>\n\n\n\n<li><strong>Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL)<\/strong><br>A rare but documented form that occurs&nbsp;<strong>years to decades after implantation<\/strong>&nbsp;in the serous cavity (e.g., around breast implants) manifests<br>Clinically as&nbsp;<strong>serous exudate<\/strong>&nbsp;with lymphocytic infiltration. Mostly&nbsp;<strong>ALK-negative<\/strong>,&nbsp;<strong>CD30-positive<\/strong>,&nbsp;<strong>EMA negative<\/strong><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Morphologie\"><\/span><strong>Morphology<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Characteristic are&nbsp;<strong>\u201eHallmark Cells\u201c<\/strong>, large, anaplastic cells with eccentrically located, horseshoe-shaped nuclei and&nbsp;<strong>perinuclear eosinophilic halo<\/strong>.<\/li>\n\n\n\n<li>Morphological Variants&nbsp;<strong>common<\/strong>,&nbsp;<strong>lymphohistiocytic<\/strong>,&nbsp;<strong>Hodgkin-like<\/strong>,&nbsp;<strong>small cell<\/strong>&nbsp;(often misdiagnosed) and&nbsp;<strong>Combination types<\/strong><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-16\"><\/span>Differential diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The diagnosis is based on a combination of&nbsp;<strong>morphological, immunohistochemical, and molecular biological analysis<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Immunohistochemistry (IHC)<\/strong><br>- <strong>positive<\/strong>CD30 (constant), CD2, CD3, CD5, CD7, CD45RO, Granzyme B, Perforin, TIA-1, EMA (only in ALK+).<br>- <strong>ALK Expression<\/strong> \u2013 Core-positive in ALK+ ALCL;&nbsp;<strong>central differentiation<\/strong>&nbsp;from ALK\u2013 ALCL<\/li>\n\n\n\n<li><strong>Molecular biology<\/strong><br>- <strong>FISH<\/strong>&nbsp;and&nbsp;<strong>PCR<\/strong>Proof of&nbsp;<strong>t(2;5)(p23;q35)<\/strong>-Translocation (NPM-ALK) in ALK+ ALCL<br>- <strong>Next-generation sequencing<\/strong>Identifies prognostically relevant rearrangements<br>\u2013 \u2013 <strong>DUSP22\/IRF4 Rearrangement<\/strong>&nbsp;\u2192 better prognosis<br>\u2013 \u2013 <strong>TP63 Rearrangement<\/strong>&nbsp;worse prognosis<\/li>\n\n\n\n<li><strong>Differential diagnoses<\/strong><br>- <strong>Hodgkin's lymphoma<\/strong>CD30+ and CD15+; but&nbsp;<strong>CD20+<\/strong>,&nbsp;<strong>CD30-<\/strong>&nbsp;in Reed-Sternberg cells,&nbsp;<strong>ALK-negative<\/strong>.<br>- <strong>Anaplastic large cell lymphoma (ALCL)<\/strong>CD20+ (compared to CD30+ in ALCL),&nbsp;<strong>CD30-<\/strong>,&nbsp;<strong>ALK-negative<\/strong><br>- <strong>Primary cutaneous CD30-positive lymphomas<\/strong><br>\u2013 \u2013 <strong>ALK-negative<\/strong>,&nbsp;<strong>EMA-negative<\/strong>,&nbsp;<strong>More favorable forecast<\/strong><br>- <strong>Angioimmunoblastic T-cell lymphoma (AITL)<\/strong><br>\u2013 \u2013 <strong>T-follicle helper phenotype<\/strong>,&nbsp;<strong>TET2\/RHOA\/IDH2 mutations<\/strong>,&nbsp;<strong>Coombs-positive<\/strong>,&nbsp;<strong>Polyclonal hypergammaglobulinemia<\/strong><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-15\"><\/span>Therapy<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Systemic ALCL (ALK+)<\/strong><br>- <strong>default<\/strong>:&nbsp;<strong>CHOP therapy<\/strong>&nbsp;(Cyclophosphamide, Doxorubicin, Vincristine, Prednisone)<br>- <strong>Combination with Brentuximab Vedotin (BV)<\/strong>:&nbsp;<strong>high response rate (86 %)<\/strong>, improved&nbsp;<strong>Disease-free and overall survival<\/strong>&nbsp;(ECHELON-2 Study)<\/li>\n\n\n\n<li><strong>ALK-ALCL<\/strong><br>\u2013 Less sensitive to CHOP;&nbsp;<strong>BV combination<\/strong>&nbsp;is a central therapeutic option<br>New approaches:<br>- <strong>5-Azacytidine<\/strong>&nbsp;Demethylation<br>- <strong>CAR-T cells<\/strong>&nbsp;against CD30<\/li>\n\n\n\n<li><strong>BIA-ALCL<\/strong><br>- <strong>Implant and capsule removal<\/strong>;&nbsp;<strong>chemotherapy aftercare<\/strong>&nbsp;during spread (e.g., CHOP + BV)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-14\"><\/span>Forecast<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>Inexpensive<\/strong>&nbsp;\u2013 5-year survival rate&nbsp;<strong>70\u201390 %<\/strong><\/li>\n\n\n\n<li><strong>ALK-ALCL<\/strong><br><strong>Unfavorable<\/strong>&nbsp;\u2013 5-year survival rate&nbsp;<strong>40-60 %<\/strong><\/li>\n\n\n\n<li><strong>CALCL<\/strong><br><strong>Very good<\/strong>&nbsp;\u2013 10-year survival rate &gt;90% %<\/li>\n\n\n\n<li><strong>BIA-ALCL<\/strong><br><strong>Inexpensive<\/strong>, if detected and treated early (implant removal)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>molecular subclassification<\/strong>&nbsp;(ALK, DUSP22, TP63) is crucial for prognosis and treatment planning.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Mycosis_fungoides\"><\/span><strong>Mycosis fungoides<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong><br>Mycosis fungoides<\/strong>&nbsp;is the most common primary cutaneous T-cell lymphoma, a form of non-Hodgkin lymphoma that primarily affects the skin.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It is characterized by clonal proliferation of atypical T-lymphocytes in the skin and belongs to the cutaneous T-cell lymphomas, which account for approximately 70 % of all primary cutaneous lymphomas.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild_und_klinisch-morphologische_Merkmale\"><\/span>Clinical picture and clinical-morphological features<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The illness typically progresses through three stages:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Eczema stage<\/strong><br>Chronic, itchy, sharply demarcated, erythematous-scaling patches that can persist for years to decades<\/li>\n\n\n\n<li><strong>Infiltration stadium<\/strong><br>Ingrowth of brownish, raised plaques into existing lesions, often with preserved areas of healthy skin&nbsp;<\/li>\n\n\n\n<li><strong>Tumor stage<\/strong><br>Training of hemispherical, ulcerating tumors that tend to superinfection and can lead to a generalization process with lymph node and organ involvement (liver, spleen, lungs, CNS).&nbsp;<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Variations<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Folliculotropic Mycosis Fungoides (FMF)<\/strong><br>Characterized by follicularly prominent, cone-shaped, skin-colored horny papules, often with alopecia (e.g., eyebrows, hairline), acne-like lesions, and cysts in the facial and neck area. The epidermis usually remains unaffected (\u201esmooth surface epidermis\u201c).<\/li>\n\n\n\n<li><strong>Pagetoid reticulosis<\/strong><br>Localized, demarcated lesions with marked intraepidermal proliferation of neoplastic T-cells, mostly on the extremities.<\/li>\n\n\n\n<li><strong>Granulomatous lax skin (GLS)<\/strong><br>Rare form with flaccid, dangling skin in the large skin folds, accompanied by granulomatous tissue changes and loss of elastic fibers. Poorer prognosis than classic MF.<\/li>\n\n\n\n<li><strong>Hypopigmented mycosis fungoides<\/strong>Poikilodermatous variant with good prognosis.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_-methodik-3\"><\/span>Differential diagnosis and methodology<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The diagnosis is challenging, as the clinical picture is often atypical and the average duration between initial manifestation and diagnosis is 3\u20134 years. Crucial is the&nbsp;<strong>histopathologic evidence<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Characteristic histological features<\/strong><br>Bandlike lymphocytic infiltrate in the upper dermis and&nbsp;<strong>Pautrier microabscesses<\/strong>&nbsp;in the epidermis<\/li>\n\n\n\n<li><strong>Immunohistology<\/strong><br>CD3+, CD4+, CD8\u2013, CD45Ro+, CD45Ra\u2013 (memory T helper phenotype). CD30 may be positive in advanced stages<\/li>\n\n\n\n<li><strong>Molecular biology<\/strong><br>Clonal T-cell receptor gene rearrangement (may be absent in early lesions)<\/li>\n\n\n\n<li><strong>Imaging<\/strong><br>CT, MRI, PET-CT for staging (especially for suspected extracutaneous involvement)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Differential diagnoses<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>S\u00e9zary syndrome<\/strong><br>Erythroderma (&gt;80% % body surface area), lymphadenopathy, S\u00e9zary cells in peripheral blood.<\/li>\n\n\n\n<li><strong>Urticaria pigmentosa<\/strong><br>Gray-brown spots with urticarial reaction (missing in MF)<\/li>\n\n\n\n<li><strong>Ringworm<\/strong><br>Edema, desquamation, mycological culture<\/li>\n\n\n\n<li><strong>Other cutaneous T-cell lymphomas<\/strong><br>No staged progression, mostly primary nodule formation<\/li>\n\n\n\n<li><strong>Primary cutaneous B-cell lymphomas<\/strong><br>The phased progression is also missing here; histologically proven<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-16\"><\/span>Therapy<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The therapy is guided by the stage of the disease:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Early stage (patches\/plaques)<\/strong><br>Local therapy with&nbsp;<strong>PUVA<\/strong>,&nbsp;<strong>Narrowband UVB<\/strong>, Glucocorticoid external or&nbsp;<strong>Aggressive topical radiotherapy<\/strong>&nbsp;(especially with FMF)<\/li>\n\n\n\n<li><strong>Advanced stage<\/strong><br>Combination of&nbsp;<strong>PUVA + Retinoids<\/strong>&nbsp;(e.g., Acitretin &gt;10 mg\/day),&nbsp;<strong>Interferon-\u03b1<\/strong>, local radiation therapy (3\u20135 Gy).&nbsp;<\/li>\n\n\n\n<li><strong>Stage IIb and beyond<\/strong><br>Chemotherapy (CHOP, Doxorubicin, Gemcitabine)<br>experimental:&nbsp;<strong>Allogene stem cell transplant<\/strong><\/li>\n\n\n\n<li><strong>Palliative therapy in tumor stage<\/strong><br>Chlorambucil or polychemotherapy<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-15\"><\/span>Forecast<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Early stage<\/strong><br>Good prognosis, remission possible, average life expectancy 7\u201310 years after diagnosis<\/li>\n\n\n\n<li><strong>Advanced stage<\/strong><br>Prognosis significantly worse; 5-year survival rate for stage IIA FMF: 87 %, for IIb: 83 %<\/li>\n\n\n\n<li><strong>GSS<\/strong>*<br>5-year survival rate about 60 %<br>*<strong>Granulomatous Slack Skin<\/strong> \u2013 a very rare variant of mycosis fungoides (MF), which is classified as a primary cutaneous T-cell lymphoma<\/li>\n\n\n\n<li><strong>Transformation into large cell lymphoma<\/strong>&nbsp;(approx. 25 % of cases)<br>Significantly worsens the prognosis<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Prognostic factors<\/strong><br>Stage at diagnosis, extent of skin involvement, lymph node involvement, extracutaneous manifestations.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Early and aggressive therapy improves quality of life and slows disease progression.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Sezary-Syndrom\"><\/span>S\u00e9zary syndrome<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>S\u00e9zary Syndrome (SS)<\/strong>&nbsp;is an aggressive form of primary cutaneous T-cell lymphoma (CTCL) and is characterized by the classic&nbsp;<strong>Triad of erythroderma, generalized lymphadenopathy, and circulating atypical T lymphocytes (S\u00e9zary cells)<\/strong>&nbsp;in the peripheral blood.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It represents the leukemic variant of cutaneous T-cell lymphomas and typically occurs in the fifth decade of life, more commonly in men. The disease progresses more rapidly than mycosis fungoides and has an unfavorable prognosis.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild-3\"><\/span>Clinical picture<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Skin manifestations<\/strong>: Include a&nbsp;<strong>scaling, generalized erythroderma<\/strong>&nbsp;with severe itching (pruritus), often accompanied by&nbsp;<strong>Alopecia<\/strong>&nbsp;hair loss,&nbsp;<strong>Nail malformations (onychodystrophy)<\/strong>,&nbsp;<strong>Palmoplantar hyperkeratosis<\/strong>&nbsp;and&nbsp;<strong>Ectropion<\/strong>&nbsp;(Eyelid displacement). The skin can&nbsp;<strong>Lion face<\/strong>&nbsp;(lion-like face).&nbsp;<\/li>\n\n\n\n<li><strong>Systemic symptoms<\/strong>Common complaints include&nbsp;<strong>general fatigue, feeling cold, and shivering<\/strong>. Other signs are&nbsp;<strong>Hepatosplenomegaly<\/strong>&nbsp;and lymph node enlargement.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Morphologie-2\"><\/span>Morphology<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Morphological features of S\u00e9zary cells<\/strong><br>Characterized by&nbsp;<strong>cerebriform (convoluted) nuclei<\/strong>, are typically&nbsp;<strong>CD4-positive, CD7-negative, and CD26-negative<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The circulating cells are detected in the blood, with a&nbsp;<strong>Count of \u22651000 S\u00e9zary cells\/mm\u00b3<\/strong>&nbsp;is considered diagnostic.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-17\"><\/span>Differential diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The differential diagnosis of S\u00e9zary syndrome is crucial, as it can be confused with other conditions clinically and histologically.<br><strong>Important differential diagnoses:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Mycosis fungoides<\/strong>&nbsp;(most common form of CTCL)<br>The distinction is made primarily by&nbsp;<strong>Blood involvement<\/strong>&nbsp;(in late stages, not in early MF stages)<\/li>\n\n\n\n<li><strong>Inflammatory dermatoses<\/strong><br>- <strong>Atopic Dermatitis (Eczema)<\/strong>,<br>- <strong>Psoriasis<\/strong><br>- <strong>Pityriasis rubra pilaris<\/strong><\/li>\n\n\n\n<li><strong>Other cutaneous lymphomas<\/strong><br>Other primary CTCL subtypes such as folliculotropic MF, pagetoid reticulosis.&nbsp;<\/li>\n\n\n\n<li><strong>Medication side effects<\/strong>&nbsp;and&nbsp;<strong>systemic diseases<\/strong>&nbsp;with erythrodermic manifestations<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methodik-3\"><\/span><strong>Diagnostic Methodology<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Clinical examination<\/strong>&nbsp;with a focus on skin changes, lymph nodes, and blood count.<\/li>\n\n\n\n<li><strong>Histopathology of skin biopsy<\/strong><br>often shows a non-specific \u201epseudo-dermatitis\u201c picture in the early stage; in the advanced stage are&nbsp;<strong>cerebriform nuclei<\/strong>&nbsp;and&nbsp;<strong>band-shaped infiltrates<\/strong>&nbsp;visible<\/li>\n\n\n\n<li><strong>Flow cytometry of peripheral blood<\/strong><br>Proof of&nbsp;<strong>CD4+\/CD8\u2013 T cells with CD7 and CD26 negativity<\/strong>&nbsp;and&nbsp;<strong>CD4\/CD8 ratio \u226510<\/strong><\/li>\n\n\n\n<li><strong>Molecular biology analyses<\/strong><br><strong>Clonality detection<\/strong>&nbsp;(T-cell receptor gene PCR) in blood and skin, as&nbsp;<strong>clonal T-cell expansion<\/strong>&nbsp;a central feature is<\/li>\n\n\n\n<li><strong>Imaging procedures<\/strong><br>Sonography, CT, PET-CT for staging and detection of extracutaneous involvement.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-17\"><\/span>Therapy<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The therapy is&nbsp;<strong>stage-dependent and usually palliative<\/strong>, with the goal of symptom control and delaying progression.&nbsp;<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>First line<\/strong><br>- <strong>PUVA therapy<\/strong>&nbsp;(Psoralen + UV-A)<br>- <strong>Extracorporeal Photopheresis (ECP)<\/strong> especially effective in pregnancy<br>- <strong>Topical corticosteroids or retinoids<\/strong>&nbsp;(e.g., Bexarotene)<br>- <strong>Combination therapy<\/strong> ECP with&nbsp;<strong>low-dose methotrexate<\/strong>,&nbsp;<strong>Interferon-Alpha<\/strong>&nbsp;or&nbsp;<strong>Bexarotene<\/strong>&nbsp;<\/li>\n\n\n\n<li><strong>Second line (advanced \/ refractory)<\/strong><br>- <strong>Chemotherapy<\/strong>&nbsp;with&nbsp;<strong>Liposomal Doxorubicin<\/strong>,&nbsp;<strong>Gemcitabine<\/strong>,&nbsp;<strong>Alemtuzumab<\/strong><br>- <strong>Monoclonal antibodies<\/strong> - <strong>Mogamulizumab<\/strong>&nbsp;(anti-CCR4) approved in the EU since 2018<\/li>\n\n\n\n<li><strong>Radical therapy options<\/strong><br>- <strong>Allogeneic stem cell transplantation<\/strong>&nbsp;in younger patients with a refractory course<br>- <strong>Whole-skin electron beam therapy<\/strong>&nbsp;in case of local progression<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-16\"><\/span>Forecast<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The prognosis for S\u00e9zary syndrome is&nbsp;<strong>unfavorable<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Median survival approximately 5 years<\/strong><\/li>\n\n\n\n<li>The survival time is determined by&nbsp;<strong>Initial symptoms, blood involvement, and disease progression<\/strong>&nbsp;influences<\/li>\n\n\n\n<li>The&nbsp;<strong>The 5-year survival rate is about 50 %<\/strong>&nbsp;<\/li>\n\n\n\n<li>One&nbsp;<strong>Poorer prognosis<\/strong>&nbsp;compared to mycosis fungoides, especially in advanced stages and with a high number of Sezary cells in the blood<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The diagnosis of S\u00e9zary syndrome requires a&nbsp;<strong>multimodal approach<\/strong>&nbsp;with clinical, histological, flow cytometry, and molecular biology clonality analysis.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The therapy is multifaceted and stage-dependent, with new approaches like mogamulizumab and stem cell transplantation expanding treatment options.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The prognosis remains limited despite progress.<\/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>Primary cutaneous anaplastic large cell CD30-positive lymphoma (cALCL)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Primary cutaneous anaplastic large cell CD30-positive lymphoma (cALCL) is a rare but clinically benign form of cutaneous lymphoma that is significantly different from systemic ALCL.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It occurs&nbsp;<strong>primarily in men over 60<\/strong>&nbsp;and is through&nbsp;<strong>rapidly growing, often solitary or grouped nodules or plaques<\/strong>&nbsp;characterized that often&nbsp;<strong>ulcerate<\/strong>&nbsp;can.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In some cases, a&nbsp;<strong>spontaneous regression<\/strong>&nbsp;possible. The prognosis is&nbsp;<strong>very good<\/strong>, with a&nbsp;<strong>10-year survival rate of over 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>Clinical and Morphological Picture<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Clinical<\/strong><br>Red, brownish-red, or bluish-red, smooth nodules or plaques, often on the head, neck, or body.&nbsp;<\/li>\n\n\n\n<li><strong>Histological<\/strong><br>Diffuse infiltrate in the dermis and upper subcutis, epidermis mostly free<br>The tumor cells show typical&nbsp;<strong>Anaplastic features<\/strong>:<br>eccentrically located, horseshoe-shaped nucleus, eosinophilic perinuclear zone in the cytoplasm<\/li>\n\n\n\n<li><strong>Immunophenotype<\/strong><br>- <strong>CD30-positive<\/strong>&nbsp;(constant)<br>- <strong>ALK-negative<\/strong><br>- <strong>EMA-negative<\/strong><br>- <strong>CD2, CD3, CD5, CD7, CD45RO<\/strong>&nbsp;positive (T-cell phenotype)<br>- No expression of ALK protein, which differentiates systemic ALCL<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_-methodik-4\"><\/span>Differential diagnosis and methodology<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The differential diagnosis is crucial, as there can be clinical and histological overlaps.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Important differential diagnoses:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Systemic anaplastic large cell lymphoma (sALCL)<\/strong><br>Distinction is made by&nbsp;<strong>Absence of extracutaneous manifestations<\/strong>&nbsp;(Bone marrow, lymph nodes, organs) in cALCL<br><strong>ALK Status<\/strong>&nbsp;is crucial: sALCL is often ALK-positive, cALCL ALK-negative<\/li>\n\n\n\n<li><strong>Diffuse large B-cell lymphoma (DLBCL)<\/strong><br>Clinically similar lesions. Differentiation by&nbsp;<strong>negative B-cell phenotype (CD20-, CD79a-, CD10-)<\/strong>,&nbsp;<strong>positive CD30<\/strong>&nbsp;at CALCL<br>Molecular detection of&nbsp;<strong>Clonal immunoglobulin heavy chain rearrangement<\/strong>&nbsp;helps with DLBCL<\/li>\n\n\n\n<li><strong>Reactive B-cell pseudolymphomas (B-PSL)<\/strong><br>Histologically similar infiltrates, but&nbsp;<strong>non-clonal<\/strong>,&nbsp;<strong>CD30-negative<\/strong>,&nbsp;<strong>no anaplasia<\/strong><\/li>\n\n\n\n<li><strong>Mycosis fungoides (MF)<\/strong><br>Can be associated with CD30-positive cells.<br>Differentiation through&nbsp;<strong>T-cell phenotype (CD4+, CD5-, CD7-)<\/strong><br><strong>no CD30 expression<\/strong>&nbsp;in classic MF<\/li>\n\n\n\n<li><strong>Cutaneous lymphoma with CD30-positive pseudolymphoma (LPE)<\/strong><br>Clinically and histologically similar images.<br>Diagnosis requires&nbsp;<strong>Combination of clinical picture, histological morphology, and immunophenotyping<\/strong>.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-18\"><\/span>Therapy<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Primary<\/strong><br><strong>Irradiation<\/strong>&nbsp;(individually or localized) or&nbsp;<strong>Excision<\/strong>&nbsp;in solitary lesions<\/li>\n\n\n\n<li><strong>Alternative<\/strong><br><strong>Rituximab<\/strong>&nbsp;monoclonal anti-CD20 antibodies,&nbsp;<strong>Interferon-alfa (low dose)<\/strong><\/li>\n\n\n\n<li><strong>Polychemotherapy (e.g., CHOP regimen)<\/strong>&nbsp;only in case of multiple or recurrent lesions, rarely necessary<\/li>\n\n\n\n<li><strong>None<\/strong>&nbsp;Systemic chemotherapy for isolated cutaneous involvement<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-17\"><\/span>Forecast<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Very good<\/strong> \u2013 10-year survival rate &gt; 90 %<\/li>\n\n\n\n<li><strong>Extracutaneous metastases are extremely rare<\/strong><\/li>\n\n\n\n<li><strong>Relapse<\/strong>&nbsp;can occur, but mostly locally and well treatable<\/li>\n\n\n\n<li><strong>Transformation into highly malignant forms<\/strong>&nbsp;is very rare<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The diagnosis requires a&nbsp;<strong>multimodal approach<\/strong>:&nbsp;<strong>Clinical assessment, histological examination, immunohistochemistry (especially CD30, ALK, CD20, CD3, CD45RO)<\/strong>&nbsp;and where applicable&nbsp;<strong>molecular biological analyses (e.g., clonal immunoglobulin rearrangement)<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Differentiation from systemic ALCL is crucial for therapy and prognosis.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"KML\"><span class=\"ez-toc-section\" id=\"Kutanes_Marginalzonen-Lymphom\"><\/span><strong>Cutaneous marginal zone lymphoma<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The <strong>Primary cutaneous marginal zone lymphoma (PCMZL)<\/strong>&nbsp;is a low-grade B-cell lymphoma that primarily occurs in the skin and is characterized by a slow-growing, benign course.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It represents a cutaneous equivalent of MALT lymphomas (mucosa-associated lymphoid tissue) and is therefore occasionally also referred to as&nbsp;<strong>SALT Lymphoma<\/strong>&nbsp;(skin-associated lymphoid tissue).&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>Clinical picture and clinical-morphological features<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Presentation<\/strong><br>Typically as&nbsp;<strong>multiple, single, or grouped papules, plaques, or nodular infiltrates<\/strong>&nbsp;to the&nbsp;<strong>limbs, torso, or neck<\/strong><\/li>\n\n\n\n<li><strong>Clinical presentation<\/strong><br>Reddish-brown, sharply demarcated, often slightly scaly or indurated skin lesions with slow progression in size<\/li>\n\n\n\n<li><strong>Histological features<\/strong><br>Knotty to diffuse infiltrates&nbsp;<strong>small to medium lymphocytes<\/strong>, which are primarily located in the dermis.<br>The tumor cells are&nbsp;<strong>bcl-2-positive<\/strong>, show no epidermotropism and exhibit characteristic&nbsp;<strong>Mantle zone-like structures<\/strong>&nbsp;on.<br>In the immunostaining,&nbsp;<strong>CD20+, CD79a+, CD5-, CD10-, CD23-<\/strong>&nbsp;and&nbsp;<strong>Membrane immunoglobulins<\/strong>&nbsp;expresses<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_-methodik-5\"><\/span><strong>Differential diagnosis and methodology<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The differential diagnosis is difficult due to the morphological similarity with reactive processes and other cutaneous lymphomas.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Important differential diagnoses include:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Reactive B-cell pseudolymphomas (B-PSL)<\/strong><br>Clinically and histologically often difficult to differentiate<br>Crucial is the&nbsp;<strong>clinicopathological correlation<\/strong>&nbsp;and the&nbsp;<strong>Clonality detection<\/strong>&nbsp;(e.g., by PCR for clonal immunoglobulin heavy chain rearrangements)<\/li>\n\n\n\n<li><strong>Follicular Lymphoma (PCFCL)<\/strong><br>Can be morphologically similar<br>Differentiation by immunohistochemistry (e.g., BCL6 expression, CD10)<\/li>\n\n\n\n<li><strong>Diffuse large B-cell lymphoma (DLBCL)<\/strong><br>Shows a more aggressive growth pattern, larger cells, a higher proliferation index (Ki-67), and is&nbsp;<strong>CD20+<\/strong>, but often&nbsp;<strong>BCL2-positive and MYC-positive<\/strong>&nbsp;Double-hit lymphoma<\/li>\n\n\n\n<li><strong>Reactive germinal centers<\/strong>&nbsp;in inflammatory diseases<br>Through&nbsp;<strong>Immunohistochemistry (e.g., CD10, BCL6, MUM1)<\/strong>&nbsp;and&nbsp;<strong>Clonality analysis<\/strong>&nbsp;to differentiate<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostik-2\"><\/span><strong>Diagnostics<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Atraumatic, large-area punch biopsy<\/strong>&nbsp;(at least 4\u20136 mm) for adequate histological and immunohistochemical assessment<\/li>\n\n\n\n<li><strong>Immunohistochemistry<\/strong><br>CD20, CD79a, CD5, CD10, CD23, BCL6, MUM1, bcl-2, CD21 (for FDC network)<\/li>\n\n\n\n<li><strong>Molecular biological clonality test<\/strong><br>PCR or Southern Blot for Immunoglobulin Genes<\/li>\n\n\n\n<li><strong>Staging<\/strong><br>Imaging procedures (CT, PET-CT) to rule out extracutaneous involvement, as PCMZL is primarily cutaneous<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-19\"><\/span><strong>Therapy<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Asymptomatic, limited lesions<\/strong><br><strong>\u201eWatch-and-wait strategy<\/strong>&nbsp;(watchful waiting, no immediate therapy)<\/li>\n\n\n\n<li><strong>Local therapy<\/strong><br><strong>Excision<\/strong>&nbsp;individual lesions or&nbsp;<strong>local radiotherapy<\/strong>&nbsp;(e.g. 20\u201330 Gy).<\/li>\n\n\n\n<li><strong>Multifocal involvement<\/strong><br>Local therapy in combination with systemic options such as&nbsp;<strong>Rituximab<\/strong>&nbsp;(CD20 antibody),&nbsp;<strong>Immunomodulators (e.g., interferon-\u03b1)<\/strong>&nbsp;or&nbsp;<strong>Oral chemotherapy (e.g., chlorambucil)<\/strong><\/li>\n\n\n\n<li><strong>Rare<\/strong> necessary \u2013 With progression or spread&nbsp;<strong>systemic chemotherapy<\/strong>&nbsp;(e.g. R-CHOP)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-18\"><\/span><strong>Forecast<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Very good<\/strong> Five-year survival rates&nbsp;<strong>90 %<\/strong><\/li>\n\n\n\n<li>The disease progresses&nbsp;<strong>slowly progressive<\/strong>, with rare, localized recurrences<\/li>\n\n\n\n<li><strong>Metastases to lymph nodes or internal organs are rare.<\/strong><\/li>\n\n\n\n<li><strong>Secondary lymphoma<\/strong>&nbsp;(e.g., Hodgkin lymphoma) can in up to&nbsp;<strong>1\/3 of cases<\/strong>&nbsp;occur and indirectly influence the prognosis<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The diagnosis requires a&nbsp;<strong>exact clinicopathological correlation<\/strong>&nbsp;And is not solely based on molecular biological findings.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The current S2k guideline (2021) emphasizes the central role of clinical presentation in the classification of cutaneous lymphomas.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Kutanes_Lymphom_mit_korniger_Mittelfingertatowierung\"><\/span><strong>Cutaneous lymphoma with granular middle finger tattoo<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The <strong>Cutaneous lymphoma<\/strong>&nbsp;is a heterogeneous group of malignant diseases that primarily manifest in the skin and arise from T or B lymphocytes.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The clinical presentation can vary widely and is often nonspecific, making diagnosis difficult.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">One&nbsp;<strong>Gritty middle finger tattoo<\/strong>&nbsp;could indicate a local skin change in the context of cutaneous lymphoma, especially if associated with a slowly growing, reddish to brownish plaque or nodule.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This change can develop over months to years and is typically&nbsp;<strong>not painful, but often itchy<\/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>Clinical picture and clinical-morphological features<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Mycosis fungoides (MF)<\/strong><br>the most common form of cutaneous T-cell lymphoma (approx. 75\u201380 %) typically progresses in three stages:<br>- <strong>Patch stadium<\/strong><br>Flat, sharply demarcated, erythematous, slightly scaly macules (similar to eczema), mostly on the trunk, flexural surfaces of the extremities, or body parts without sun exposure<br>- <strong>Plaquestadium<\/strong><br>Elevated, reddish-livid to brownish plaques with scales, crusts, and lichenification; often persists for 2-5 years<br>- <strong>Tumor stage<\/strong><br>Hemispherical or lobed tumors, possibly with ulceration and superinfection; occurs in 10\u201320 %<\/li>\n\n\n\n<li><strong>S\u00e9zary Syndrome (SS)<\/strong><br>Leukemic equivalent of MF with generalized erythroderma, intense itching, lymph node enlargement, nail dystrophy, and detection of atypical lymphoid cells (S\u00e9zary cells) in the blood.<\/li>\n\n\n\n<li><strong>Lymphomatoid Papulosis (LyP)<\/strong><br>Characterized by grouped, spontaneously regressing papules and nodules that disappear within weeks<br>Histologically, various types show overlap with aggressive CTCL, which is why clinicopathological correlation is crucial<\/li>\n\n\n\n<li><strong>Primary cutaneous anaplastic large cell lymphoma (cALCL)<\/strong><br>Solitary erythematous to brownish nodules, possibly with ulceration<br>CD30-positive, but mostly ALK-negative<br>Spontaneous regression possible (approx. 20 %)<\/li>\n\n\n\n<li><strong>Primary cutaneous CD8-positive acral T-cell lymphoma (CD8+ ATCL)<\/strong><br>Solitary or bilateral nodules in acral locations (e.g., face, ears, feet)<br>histologically dense infiltrates of small to medium-sized atypical lymphocytes without epidermotropism<br><strong>excellent prognosis<\/strong>.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnose_und_Diagnostik\"><\/span>Differential diagnosis and diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The differential diagnosis is crucial, as cutaneous lymphomas can often be mistaken for inflammatory or benign skin diseases:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Inflammatory skin diseases<\/strong><br>Psoriasis, atopic dermatitis, contact dermatitis, lichen planus<\/li>\n\n\n\n<li><strong>Benign lymphoproliferations<\/strong><br>Pseudolymphoma, lymphomatoid papulosis (LyP)<\/li>\n\n\n\n<li><strong>Other malignant diseases<\/strong><br>Melanoma, cutaneous Merkel cell carcinoma, cutaneous diffuse large B-cell lymphoma (aggressive course)<\/li>\n\n\n\n<li><strong>Infectious diseases<\/strong><br>Tuberculosis, leprosy, fungal infections<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostikmethodik\"><\/span><strong>Diagnostic Methodology<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Medical history and physical examination<\/strong><br>Long-term course, localization, symptoms (itching, pain)<\/li>\n\n\n\n<li><strong>Skin biopsy with histological and immunohistochemical analysis<\/strong><br>Detection of tumor cells (CD3, CD4, CD8, CD30, TCR-genes), epidermotropism, clonality<\/li>\n\n\n\n<li><strong>Clonality analysis<\/strong>&nbsp;(PCR for TCR-gamma or IgH genes)<br>Confirmation of neoplastic proliferation<\/li>\n\n\n\n<li><strong>Imaging procedures<\/strong><br>CT, PET-CT, MRI for staging examination (lymph nodes, organs)<\/li>\n\n\n\n<li><strong>Blood test<\/strong><br>Detection of S\u00e9zary cells in blood (in SLE), LDH, serum protein electrophoresis<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-20\"><\/span>Therapy<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The therapy is&nbsp;<strong>stage and entity dependent<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Early stages (patch\/plaque)<\/strong><br>Topical therapy (glucocorticoids class III\u2013IV),&nbsp;<strong>Phototherapy (UVB, PUVA)<\/strong>, local radiotherapy<\/li>\n\n\n\n<li><strong>Advanced Stages (Tumor Stage, SS)<\/strong><br>Systemic therapies (retinoids, interferon-\u03b1, cytostatics),&nbsp;<strong>Targeted therapies<\/strong>&nbsp;Mogamulizumab (CCR4), Brentuximab Vedotin (CD30), Histone deacetylase inhibitors<\/li>\n\n\n\n<li><strong>Aggressive forms (e.g., cutaneous gamma-delta T-cell lymphoma)<\/strong><br>Polychemotherapy, hematopoietic stem cell transplantation<\/li>\n\n\n\n<li><strong>CD8+ acral T-cell lymphoma<\/strong><br>Surgical excision or radiation therapy are sufficient;&nbsp;<strong>no systemic therapy required<\/strong><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-19\"><\/span>Forecast<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Mycosis fungoides<\/strong><br>5-year survival rate 20\u201360 %; extracutaneous dissemination possible<\/li>\n\n\n\n<li><strong>S\u00e9zary syndrome<\/strong><br>Poor prognosis, median survival time under 3 years<\/li>\n\n\n\n<li><strong>Lymphomatoid Papulosis<\/strong><br><strong>Excellent prognosis<\/strong>, 5- and 10-year survival rate close to 100 %<\/li>\n\n\n\n<li><strong>CD8+ acral T-cell lymphoma<\/strong><br><strong>Excellent forecast<\/strong>, no deaths from the disease known<\/li>\n\n\n\n<li><strong>Primary cutaneous anaplastic large cell lymphoma<\/strong>Favorable prognosis, spontaneous regression possible<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>clinicopathological correlation<\/strong>&nbsp;is crucial for correct diagnosis and treatment planning.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In therapy-refractory, eczematous lesions, a cutaneous lymphoma should be considered early on.<\/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>B-lymphoblastic lymphoma\/leukemia (B-ALL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The <strong>B-lymphoblastic lymphoma\/leukemia (B-ALL)<\/strong>&nbsp;is an aggressive, acute neoplasm of B-cell precursor cells that can clinically manifest as leukemia or lymphoma.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The differential diagnosis includes other lymphoid neoplasms, particularly&nbsp;<strong>diffuse large B-cell lymphoma (DLBCL)<\/strong>, the&nbsp;<strong>Burkitt's lymphoma<\/strong>&nbsp;and&nbsp;<strong>Acute T-cell leukemia (T-ALL)<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Differentiated diagnostics are crucial, as therapy and prognosis strongly depend on the exact classification.&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>Clinical picture and clinical-morphological features<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Symptoms<\/strong><br>Bone marrow failure with anemia (fatigue, dyspnea), neutropenia (infections), thrombocytopenia (bleeding), B symptoms (fever, night sweats, weight loss). Extramedullary manifestations such as lymphadenopathy, hepato- and splenomegaly, mediastinal masses (especially in T-ALL) or CNS involvement (5-8% at diagnosis) are possible.<\/li>\n\n\n\n<li><strong>Cytomorphology<\/strong><br>Lymphoblasts with large nuclei, finely dispersed chromatin, multiple nucleoli, and scant cytoplasm. The cells show high proliferative activity (high Ki67 index).<\/li>\n\n\n\n<li><strong>Immunophenotype<\/strong><br>Positive for&nbsp;<strong>CD19, CD20, CD22, CD79a<\/strong>,&nbsp;<strong>TdT<\/strong>&nbsp;Terminal deoxynucleotidyl transferase,&nbsp;<strong>CD34<\/strong>&nbsp;(frequently),&nbsp;<strong>HLA-DR<\/strong><br>Negative for myeloid markers (CD13, CD33) and T-cell markers (CD2, CD3, CD5)<\/li>\n\n\n\n<li><strong>Genetic markers<\/strong><br>Typical translocations such as&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>, as well as&nbsp;<strong>BCR::ABL1-like<\/strong>&nbsp;Variants with activation of JAK\/STAT or ABL kinase signaling pathways.<br><strong>IKZF1 Deletions<\/strong>&nbsp;are frequent and associated with an unfavorable prognosis.<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-18\"><\/span>Differential diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Differential diagnosis<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>DLBCL (diffuse large B-cell lymphoma)<\/strong>Cell size and morphology similar, but&nbsp;<strong>TdT-negative<\/strong>,&nbsp;<strong>CD10 positive<\/strong>&nbsp;(at GCB type),&nbsp;<strong>BCL2 positive<\/strong>,&nbsp;<strong>BCL6 positive<\/strong>,&nbsp;<strong>MYC negative<\/strong>.No leukemia or bone marrow failure<\/li>\n\n\n\n<li><strong>Burkitt's lymphoma<\/strong>Similar morphology (blasts),&nbsp;<strong>MYC translocation<\/strong>&nbsp;(t(8;14)),&nbsp;<strong>high Ki67 index (&gt;95%)<\/strong>,&nbsp;<strong>CD10 positive<\/strong>,&nbsp;<strong>BCL2 negative<\/strong>.Mostly extranodal (abdomen, CNS)<\/li>\n\n\n\n<li><strong>T-ALL<\/strong>CD3+, CD7+, TdT+, absent B-cell markers, often mediastinal lymphadenopathy<\/li>\n\n\n\n<li><strong>B-cell lymphoblastic lymphoma<\/strong>Clinically similar to B-ALL, but without significant blood count changes, primarily lymphatic involvement<\/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>Diagnostic methods<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cytomorphology<\/strong>&nbsp;(peripheral blood, bone marrow, lymph node biopsy).<\/li>\n\n\n\n<li><strong>Immunophenotyping<\/strong>&nbsp;(Flow Cytometry, Immunohistochemistry).<\/li>\n\n\n\n<li><strong>Cytogenetics<\/strong>&nbsp;Karyotyping.<\/li>\n\n\n\n<li><strong>FISH<\/strong>&nbsp;(for translocations: t(9;22), t(12;21), t(1;19), IGH::IL3, CRLF2).<\/li>\n\n\n\n<li><strong>Molecular genetics (NGS)<\/strong>&nbsp;for the identification of mutations (e.g.&nbsp;&nbsp;<strong>IKZF1<\/strong>,&nbsp;<strong>PAX5<\/strong>,&nbsp;<strong>EBF1<\/strong>,&nbsp;<strong>JAK\/STAT<\/strong>,&nbsp;<strong>RAS signaling pathway<\/strong>).<\/li>\n\n\n\n<li><strong>Cerebrospinal fluid examination<\/strong>&nbsp;for suspected CNS involvement.<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-21\"><\/span>Therapy<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>First-line therapy<\/strong><br>Intensive chemotherapy regimens, e.g.&nbsp;<strong>Blinatumomab<\/strong>&nbsp;(BiTE antibodies) or&nbsp;<strong>Inotuzumab ozogamicin<\/strong>&nbsp;(Antibody-drug conjugate) in combination with chemotherapy<br>In adults:&nbsp;<strong>Hyper-CVAD<\/strong>&nbsp;(Cyclophosphamide, Vincristine, Doxorubicin, Dexamethasone) or&nbsp;<strong>Blinatumomab<\/strong><\/li>\n\n\n\n<li><strong>Allogeneic stem cell transplantation<\/strong><br>In patients with unfavorable genetics (e.g.,.&nbsp;<strong>BCR::ABL1<\/strong>,&nbsp;<strong>IKZF1 Deletion<\/strong>,&nbsp;<strong>Low white blood cell count<\/strong>), high risk or recurrence<\/li>\n\n\n\n<li><strong>CNS prophylaxis<\/strong><br>Methotrexate (intrathecal), corticosteroid therapy, often combined with systemic chemotherapy<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-20\"><\/span>Forecast<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Inexpensive<\/strong><br>T-ALL with&nbsp;<strong>t(12;21)<\/strong>,&nbsp;<strong>BCR::ABL1-negative<\/strong>,&nbsp;<strong>Older patients with low risk<\/strong><\/li>\n\n\n\n<li><strong>Unfavorable<\/strong><br><strong>BCR-ABL1-positive<\/strong>,&nbsp;<strong>BCR::ABL1-like<\/strong>&nbsp;Variations,&nbsp;<strong>IKZF1 Deletion<\/strong>,&nbsp;<strong>Low white blood cell count<\/strong>,&nbsp;<strong>older patients<\/strong>,&nbsp;<strong>CNS involvement<\/strong><br>The 5-year survival rate is about&nbsp;<strong>60\u201370%<\/strong>&nbsp;in children, significantly lower in adults (approx.&nbsp;&nbsp;<strong>40-50%<\/strong>), especially with unfavorable genetic profiles<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Modern diagnostics using&nbsp;<strong>NGS and FISH<\/strong>&nbsp;enables precise risk stratification and personalized therapeutic approaches.<\/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>T-lymphoblastic lymphoma\/leukemia (T-ALL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The <strong>T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL)<\/strong>&nbsp;are malignant diseases of lymphatic precursor cells, characterized by uncontrolled proliferation of immature T-lymphocytes (lymphoblasts).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The disease can occur primarily in the bone marrow (leukemia) or in lymph nodes and extranodal organs (lymphoma), with the distinction being made based on the proportion of blasts in the bone marrow (usually &gt;20\u201325%).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">T-ALL occurs less frequently in children and adolescents than B-ALL (approx. 15 %of all ALL cases), but is more common in adults (approx. 25 %).<br>The disease shows two incidence peaks: in childhood (under 5 years of age) and in adulthood (from 50 years of age). <\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Clinically, T-ALL typically manifests with symptoms of bone marrow failure (anemia, thrombocytopenia, neutropenia), fever, weight loss, night sweats, and bone pain.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Characteristic are&nbsp;<strong>Hepatosplenomegaly<\/strong>,&nbsp;<strong>Lymphadenopathy<\/strong>&nbsp;and in about 5\u20138 % of patients a&nbsp;<strong>CNS involvement<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In T-ALL of the T-cell type,&nbsp;<strong>Mediastinal masses<\/strong>&nbsp;in the thorax, which clinically become relevant as pressure symptoms (e.g., dyspnea, cough) or as an indication for radiation therapy.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisch-morphologische_Merkmale-8\"><\/span><strong>Clinical-morphological features<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cytomorphology<\/strong><br>Lymphoblasts show a high cell count, large nuclei with fine chromatin, and 1-3 nucleoli. The cytoplasm volume is small.<\/li>\n\n\n\n<li><strong>Immunophenotyping (central to diagnosis)<\/strong><br>Blasts express T-cell-specific surface antigens such as&nbsp;<strong>CD2, CD3, CD5, CD7<\/strong>&nbsp;(mostly very positive),&nbsp;<strong>CD1a<\/strong>&nbsp;(in thymic subtypes),&nbsp;<strong>TdT<\/strong>&nbsp;Terminal deoxynucleotidyl transferase and&nbsp;<strong>CD4\/CD8<\/strong>&nbsp;(depending on the differentiation stage: early immature, thymic, or mature T-ALL)<br><strong>CD7<\/strong>&nbsp;is positive in over 90 % of cases. A CD4+\/CD8\u2013 immunophenotype is typical of early immature T-ALL<\/li>\n\n\n\n<li><strong>Cytogenetics and molecular genetic markers<\/strong><br>Common genetic aberrations include&nbsp;<strong>t(14;14)(q11;q32)<\/strong>,&nbsp;<strong>inv(14)(q11q32)<\/strong>,&nbsp;<strong>t(X;14)(q11;q32)<\/strong>&nbsp;and&nbsp;<strong>del(11q)<\/strong><br>Additional risk markers are&nbsp;<strong>ATM Mutations<\/strong>&nbsp;(in 60 %),&nbsp;<strong>TP53 mutations<\/strong>&nbsp;(at 20\u201330 %) and&nbsp;<strong>IKZF1 Deletions<\/strong><br>The&nbsp;<strong>Next-Generation Sequencing (NGS)<\/strong>Analysis is increasingly used for the identification of complex genetic changes and for risk assessment.<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-19\"><\/span><strong>Differential diagnostics<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The differential diagnosis includes other lymphoproliferative disorders:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>B-cell ALL\/LBL<\/strong><br>Distinction by absence of T-cell antigens (CD3, CD7, CD2), positive B-cell markers (CD19, CD20, CD79a)<\/li>\n\n\n\n<li><strong>T-cell prolymphocytic leukemia (T-PLL)<\/strong><br>Distinction by slower progression, typical cell morphology (large, cerebriform nuclei), CD4+\/CD8- phenotype with&nbsp;<strong>CD26+, CD52+, TCL1A+<\/strong>, as well as&nbsp;<strong>complex karyotype<\/strong>&nbsp;and&nbsp;<strong>inv(14)<\/strong><\/li>\n\n\n\n<li><strong>Chronic lymphocytic leukemia (CLL)<\/strong><br>In T-CLL (rare), typical CLL markers (CD5+, CD23+, CD79b\u2013) are absent<\/li>\n\n\n\n<li><strong>S\u00e9zary syndrome<\/strong><br>A cutaneous T-cell lymphoma subtype with erythroderma, pruritus, alopecia, and CD4+\/CD8\u2013 phenotype with&nbsp;<strong>CD7\u2013, CD26\u2013<\/strong><\/li>\n\n\n\n<li><strong>Adult T-cell leukemia\/lymphoma (ATLL)<\/strong><br>Caused by&nbsp;<strong>HTLV-I<\/strong>, occurs in endemic areas (Japan, Caribbean)<br>shows&nbsp;<strong>CD25++<\/strong>,&nbsp;<strong>CD4+\/CD8\u2013<\/strong>,&nbsp;<strong>CD7\u2013<\/strong>,&nbsp;<strong>TP53 mutations<\/strong>&nbsp;and&nbsp;<strong>HTLV-I DNA<\/strong>&nbsp;in the blood<\/li>\n\n\n\n<li><strong>T-lymphoblastic lymphoma (T-LBL)<\/strong><br>Distinguishing T-ALL by primary extramedullary involvement (e.g., mediastinum), with little or no bone marrow involvement (&lt;20 % blasts)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostik-3\"><\/span><strong>Diagnostics<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Blood smear and bone marrow biopsy<\/strong><br>Detection of lymphoblasts (&gt;20 % in bone marrow for ALL)<\/li>\n\n\n\n<li><strong>Immunophenotyping (Flow Cytometry)<\/strong><br>Mandatory for T-cell phenotype identification<\/li>\n\n\n\n<li><strong>Chromosome analysis (karyotype)<\/strong><br>Identification of translocations such as t(14;14), inv(14)<\/li>\n\n\n\n<li><strong>FISH (fluorescence in situ hybridization)<\/strong><br>Rapid detection of cryptic aberrations (e.g.&nbsp;<strong>t(14;14)<\/strong>)<\/li>\n\n\n\n<li><strong>Molecular Genetics (PCR, NGS)<\/strong><br>Detection of fusion transcripts (e.g.&nbsp;<strong>TAL1<\/strong>,&nbsp;<strong>LYL1<\/strong>,&nbsp;<strong>HOXA<\/strong>-gene), mutations (<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>Therapy<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Induction therapy<\/strong><br>Intensive chemotherapy with steroids (e.g., dexamethasone), vincristine, cyclophosphamide, daunorubicin, and methotrexate (e.g.,.&nbsp;<strong>UKALL2003 Protocol<\/strong>)<\/li>\n\n\n\n<li><strong>Consolidation and conservation<\/strong><br>Phase of intensive therapy with central nervous system prophylaxis (e.g., intrathecal methotrexate)<\/li>\n\n\n\n<li><strong>Allogeneic stem cell transplantation (SCT)<\/strong><br>Indexed at high risk (e.g.,.&nbsp;<strong>TP53 mutation<\/strong>,&nbsp;<strong>KMT2A Rearrangement<\/strong>,&nbsp;<strong>no remission after induction<\/strong>)<\/li>\n\n\n\n<li><strong>Targeted therapy<\/strong><br>For certain subtypes (e.g.&nbsp;<strong>JAK-STAT activating mutations<\/strong>) will&nbsp;<strong>JAK inhibitors<\/strong>&nbsp;(e.g., Ruxolitinib) examined<br><strong>Blinatumomab<\/strong>&nbsp;(BiTE antibodies) are used in individual cases<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-21\"><\/span><strong>Forecast<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Unfavorable prognostic factors:<br><strong>Over 50 years old<\/strong>,&nbsp;<strong>high white blood cell count<\/strong>,&nbsp;<strong>Bone marrow infiltration<\/strong>,&nbsp;<strong>CNS involvement<\/strong>,&nbsp;<strong>TP53 mutation<\/strong>,&nbsp;<strong>ATM Mutation<\/strong>,&nbsp;<strong>KMT2A Rearrangement<\/strong>,&nbsp;<strong>T-ALL with mature phenotype<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In children, the recovery rate&nbsp;<strong>85 %<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In adults, the prognosis is worse:&nbsp;<strong>50\u201360 %<\/strong>&nbsp;achieve long-term remission<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"NK-Zell-Lymphome-2\"><\/span><strong>NK-cell lymphomas<\/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>Extranodal NK cell lymphoma<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The <strong>Extranodal NK\/T-cell lymphoma, nasal type (ENKTL-NT)<\/strong>&nbsp;is a <strong>also associated with EBV<\/strong>, rare, aggressive form of non-Hodgkin lymphoma, predominantly composed of&nbsp;<strong>natural killer cells (NK cells)<\/strong>&nbsp;or is derived from T cells and is closely related to the&nbsp;<strong>Epstein-Barr Virus (EBV) Infection<\/strong>&nbsp;associated, as if through&nbsp;<strong>CD56 positivity, EBV detection, and angiotropic growth<\/strong>&nbsp;is characterized.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It occurs primarily in Asia, Central, and South America and mainly affects adults, with men being affected more frequently.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">&nbsp;Therapy is&nbsp;<strong>combined<\/strong>&nbsp;(Radiation therapy + chemotherapy), prognosis remains&nbsp;<strong>relatively bad<\/strong>, however, the situation is improving with novel immunotherapies.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild_und_morphologische_Merkmale\"><\/span><strong>Clinical picture and morphological features<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Clinical<\/strong><br>Typical symptoms begin with chronic nasal congestion, nosebleeds, and painful, ulcerating lesions in the nasal cavity.<br>Advanced stages show centrofacial destructions, destruction of the cranial base, necroses of the alae nasi and septum, as well as B symptoms such as fever, night sweats, and weight loss.<\/li>\n\n\n\n<li><strong>Morphological<\/strong><br>Histologically, the lymphoma is characterized by&nbsp;<strong>angiocentric and angiodestructive growth<\/strong>&nbsp;with extensive coagulation necrosis<br>The tumor cells are medium to large in size, with irregular nuclei and granular chromatin. They are often surrounded by a dense infiltrate of reactive cells (lymphocytes, macrophages, eosinophils).<\/li>\n\n\n\n<li><strong>Immunophenotype<\/strong><br><strong>CD56 positive<\/strong>&nbsp;(identical to N-CAM),&nbsp;<strong>CD4 positive<\/strong>,&nbsp;<strong>CD8 negative<\/strong>,&nbsp;<strong>CD20 negative<\/strong>,&nbsp;<strong>CD30 in about 20% positive<\/strong>.<br>The&nbsp;<strong>EBV RNA Detection<\/strong>&nbsp;by means of&nbsp;<strong>EBER in situ hybridization<\/strong>&nbsp;is groundbreaking<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-20\"><\/span><strong>Differential diagnostics<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The differential diagnosis includes:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Granuloma gangrenescens nasi<\/strong>&nbsp;(older designation)<br>Inflammatory disease that can appear clinically and histologically similar but does not show malignancy<\/li>\n\n\n\n<li><strong>Infectious or granulomatous diseases<\/strong>&nbsp;(e.g., tuberculosis, leishmaniasis, sarcoidosis) \u2013 to be differentiated by clinical, microbiological, and histological examinations<\/li>\n\n\n\n<li><strong>Other T-cell lymphomas<\/strong>, especially&nbsp;<strong>Cutaneous T-cell lymphomas<\/strong>,&nbsp;<strong>angioimmunoblastic T-cell lymphoma<\/strong>&nbsp;or&nbsp;<strong>Enteropathy-associated T-cell lymphoma<\/strong>, via immunophenotyping and molecular analysis (e.g., T-cell receptor genes) differentiation<\/li>\n\n\n\n<li><strong>EBV-associated neoplasms in HIV infection<\/strong>, special consideration in immunosuppressed patients<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The differential diagnosis requires careful histological and molecular biological clarification.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostikmethodik-2\"><\/span><strong>Diagnostic Methodology<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Biopsy<\/strong>&nbsp;affected tissue (e.g., nasal septum, skin, gastrointestinal tract), central diagnostic basis<\/li>\n\n\n\n<li><strong>Immunohistochemistry<\/strong><br>Detection of CD56, CD4, CD3, CD30, CD20 (negative), and EBV (EBER hybridization)<\/li>\n\n\n\n<li><strong>Molecular biology methods<\/strong><br>Detection of clonal T-cell receptor genes (of T-cell origin), FISH for detection of gene alterations<\/li>\n\n\n\n<li><strong>Imaging<\/strong><br>CT or MRI for assessment of extent (e.g., skull base involvement, extranodal lesions)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-23\"><\/span><strong>Therapy<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Localized disease<\/strong><br><strong>Radiotherapy<\/strong>&nbsp;as standard treatment.&nbsp;<\/li>\n\n\n\n<li><strong>Systemic disease or high recurrence rate<\/strong><br><strong>Combination therapy<\/strong>&nbsp;from&nbsp;<strong>Chemotherapy<\/strong>&nbsp;(e.g., asparaginase-containing regimens such as SMILE or DA-EPOCH-R) and&nbsp;<strong>Irradiation<\/strong><\/li>\n\n\n\n<li><strong>New approaches<\/strong><br>In advanced cases,&nbsp;<strong>immunotherapeutic strategies<\/strong>&nbsp;(e.g., PD-1 inhibitors) and&nbsp;<strong>Cell therapies<\/strong>&nbsp;(e.g., CAR T-cells) evaluated in clinical trials<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-22\"><\/span><strong>Forecast<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li>The forecast is&nbsp;<strong>unfavorable<\/strong>, especially in advanced stages<\/li>\n\n\n\n<li><strong>Median survival time<\/strong>&nbsp;is about&nbsp;<strong>15\u201336 months<\/strong>, depending on the stage and response to therapy.&nbsp;<\/li>\n\n\n\n<li><strong>CD30 positivity<\/strong>&nbsp;correlates with a better prognosis (median survival &gt;35 months vs. approx. 9.6 months in CD30-negative cases)<\/li>\n\n\n\n<li><strong>EBV DNA quantity in serum<\/strong>&nbsp;can serve as a prognostic marker, high values associated with poorer prognosis<\/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>Aggressive NK-cell leukemia<\/strong> (ANKL)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Aggressive NK-cell leukemia (ANKL) is a rare, highly malignant disorder caused by the proliferation of natural killer (NK) cells, which follows a rapid, aggressive clinical course. It is strongly associated with&nbsp;<strong>Epstein-Barr Virus (EBV)<\/strong>&nbsp;associated, though EBV-negative cases are also known.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The disease is more common in Asia, particularly in Japan and Southeast Asia, than in Europe or North America.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_und_morphologisches_Bild-3\"><\/span><strong>Clinical and Morphological Picture<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Clinical picture<\/strong><br>\u2013 Rapid, aggressive course with&nbsp;<strong>B-symptoms<\/strong>&nbsp;Fever, night sweats, weight loss<br>\u2013 Common&nbsp;<strong>Hepatosplenomegaly<\/strong>&nbsp;and&nbsp;<strong>Lymphadenopathy<\/strong><br>- <strong>Pancytopenia<\/strong>&nbsp;in blood count (anemia, neutropenia, thrombocytopenia)<br>In some patients<br><strong>Insect sting hypersensitivity<\/strong>&nbsp;with pronounced swelling and necrosis<br>\u2013 Frequent complications<br><strong>Disseminated intravascular coagulation (DIC)<\/strong>,&nbsp;<strong>Hemophagocytic Syndrome (HPS)<\/strong>, Multiorgan failure<br><\/li>\n\n\n\n<li><strong>Morphological features (bone marrow biopsy)<\/strong><br>\u2013 Interstitial or sinusoidal infiltration by&nbsp;<strong>medium-sized neoplastic cells<\/strong><br>- <strong>Marked nuclear atypia<\/strong>,&nbsp;<strong>prominent nucleoli<\/strong>, focal necrosis and apoptotic cells<br>- <strong>Complete Blood Count<\/strong> Atypical leukemic cells with&nbsp;<strong>azurophilic granules<\/strong>&nbsp;and core-typical changes<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_-methodik-6\"><\/span><strong>Differential diagnosis and methodology<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The diagnosis of ANKL requires a combination of clinical, morphological, immunohistochemical, and molecular biological investigations to differentiate it from other lymphatic malignancies:<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnosen-2\"><\/span><strong>Differential diagnoses<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Diffuse large B-cell lymphoma (DLBCL)<\/strong><br>\u2013 Unlike ANKL, DLBCL are typically&nbsp;<strong>CD20-positive<\/strong>,&nbsp;<strong>CD56-negative<\/strong>&nbsp;and&nbsp;<strong>EBV-negative<\/strong><br>\u2013 Unlike ANKL, DLBCL show&nbsp;<strong>More favorable forecast<\/strong>&nbsp;during therapy with R-CHOP<\/li>\n\n\n\n<li><strong>Extranodal Natural Killer\/T-Cell Lymphoma (ENKTL)<\/strong><br>\u2013 Similar to ANKL, ENKTL are associated with EBV and show&nbsp;<strong>CD56-positive, CD2-positive, CD3-negative<\/strong><br>Differentiation: ENKTL mostly affects&nbsp;<strong>Nose and sinuses<\/strong>, while ANKL proceeds systemically<br>- <strong>EBER in situ hybridization<\/strong>&nbsp;is positive for both, but mostly in ANKL&nbsp;<strong>systemic<\/strong>&nbsp;provable<\/li>\n\n\n\n<li><strong>Peripheral T-cell lymphomas, NOS (PTCL, NOS)<\/strong><br>\u2013 PTCL, NOS are mostly&nbsp;<strong>CD56-negative<\/strong>,&nbsp;<strong>CD2-positive<\/strong>,&nbsp;<strong>T-cell receptor genes are clonally rearranged<\/strong><br>\u2013 ANKL shows&nbsp;<strong>non-clonal T-cell receptor genes<\/strong>, which&nbsp;<strong>NK cell lineage<\/strong>&nbsp;points to<\/li>\n\n\n\n<li><strong>Hemophagocytic Syndrome (HPS)<\/strong><br>ANCL can be&nbsp;<strong>underlying disease<\/strong>&nbsp;for HPS occurrences<br>differentiation<br>HPS is a&nbsp;<strong>Syndrome<\/strong>, not a neoplasm, ANKL is the&nbsp;<strong>predisposing tumor disease<\/strong>&nbsp;<\/li>\n\n\n\n<li><strong>Other EBV-associated lymphomas<\/strong>&nbsp;(e.g., Hodgkin lymphoma, EBV-positive DLBCL, NOS)<br>Distinction by&nbsp;<strong>Immunohistochemistry<\/strong>,&nbsp;<strong>EBER-ISH<\/strong>,&nbsp;<strong>Gene expression analysis<\/strong>&nbsp;and&nbsp;<strong>Clonality tests<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Your differential diagnosis requires a&nbsp;<strong>comprehensive diagnostics<\/strong>, especially&nbsp;<strong>Immunohistochemistry<\/strong>,&nbsp;<strong>EBER-ISH<\/strong>,&nbsp;<strong>PCR for T-cell receptor genes<\/strong>&nbsp;and&nbsp;<strong>molecular biology analyses<\/strong>.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostische_Methodik-4\"><\/span><strong>Diagnostic Methodology<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Immunohistochemistry<\/strong><br>- <strong>Positive<\/strong>CD2, CD16, CD56, CD45, CD43, TIA-1, Granzyme B<br>- <strong>Negative<\/strong>CD3, CD4, CD5, CD7, CD8, CD57, CD20, CD30<br>- <strong>CD56-positive<\/strong>&nbsp;is characteristic, but not specific (also in ENKTL, DLBCL)<\/li>\n\n\n\n<li><strong>Molecular biological investigations<\/strong><br>- <strong>EBER in situ hybridization<\/strong>&nbsp;(obligatorily positive in most cases)<br>- <strong>PCR of clonal T-cell receptor genes<\/strong>:&nbsp;<strong>Negative<\/strong>&nbsp;\u2013 speaks for NK cell lineage<br>- <strong>Next-generation sequencing (NGS)<\/strong><br>\u2013 \u2013 Mutations in&nbsp;<strong>JAK\/STAT signaling pathway<\/strong>&nbsp;(JAK3, STAT3),&nbsp;<strong>TP53<\/strong>,&nbsp;<strong>Deletions on chromosome 6q<\/strong><br>\u2013 \u2013 Distinction from other lymphomas by&nbsp;<strong>molecular subtyping<\/strong><\/li>\n\n\n\n<li><strong>Imaging<\/strong><br>- <strong>CT\/MRI<\/strong>&nbsp;for the assessment of hepatosplenomegaly, lymph node involvement, and extranodal lesions<br>- <strong>FDG-PET\/CT<\/strong>&nbsp;for staging and therapy monitoring (not standard, but helpful in case of complications)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-24\"><\/span><strong>Therapy<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>First-line therapy<\/strong><br>- <strong>CHOP<\/strong>&nbsp;(cyclophosphamide, doxorubicin, vincristine, prednisone) or&nbsp;<strong>R-CHOP<\/strong>&nbsp;(with Rituximab), however&nbsp;<strong>low efficacy<\/strong>&nbsp;at ANKL<br>- <strong>Etoposide-based regimens<\/strong>&nbsp;(e.g.&nbsp;<strong>Hyper-CVAD<\/strong>) are used more frequently because they respond better to more aggressive tumors<br>- <strong>Allogeneic stem cell transplantation (allo-SCT)<\/strong><br>\u2013 \u2013 <strong>Gold standard in appropriate patients<\/strong>, especially in remission<br>\u2013 \u2013 Offers the&nbsp;<strong>Best chance for long-term remission or cure<\/strong><\/li>\n\n\n\n<li><strong>Second-line therapy<\/strong><br>- <strong>CAR T-cell therapy<\/strong>&nbsp;(e.g., against CD19 or CD22), in clinical trials, limited data in ANKL<br>- <strong>Immunotherapy with anti-EBV-CTL (T-cell therapy)<\/strong>, experimental, but promising<br>- <strong>BCL2 inhibitors (Venetoclax)<\/strong>, in combination with other regimens, if BCL2 expression is present<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-23\"><\/span><strong>Forecast<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Very unfavorable<\/strong> - <strong>Median survival time is less than 12 months<\/strong><\/li>\n\n\n\n<li><strong>5-year survival rate under 20%<\/strong><\/li>\n\n\n\n<li><strong>Unfavorable prognostic factors<\/strong><br>\u2013 High LDH, B symptoms, bone marrow infiltration, DIC, hemophagocytosis<br><strong>Not responding to standard chemotherapy<\/strong>&nbsp;(e.g. R-CHOP)<\/li>\n\n\n\n<li><strong>Allogeneic stem cell transplantation<\/strong>&nbsp;is the only approach with&nbsp;<strong>potentially curative effect<\/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>Chronic NK cell leukemia<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Chronic NK-cell leukemia, also referred to as aggressive NK-cell leukemia or aggressive NK-cell lymphoma, is a rare, highly aggressive malignant disorder of natural killer cells (NK cells).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It shows a characteristic clinical-morphological and immunophenotypic profile that requires differential diagnostics.&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>Clinical picture and clinical-morphological features<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Age group<\/strong><br>Affected are primarily&nbsp;<strong>Teenagers and young adults<\/strong>, older patients are rarer<\/li>\n\n\n\n<li><strong>Clinical presentation<\/strong><br>Typically, a&nbsp;<strong>systemic infestation<\/strong>&nbsp;with&nbsp;<strong>Hepato- and splenomegaly<\/strong>,&nbsp;<strong>Lymphadenopathy<\/strong>,&nbsp;<strong>Bone marrow infiltration<\/strong>&nbsp;and&nbsp;<strong>Peripheral blood involvement<\/strong><\/li>\n\n\n\n<li><strong>Morphology<\/strong><br>In peripheral blood and bone marrow are found&nbsp;<strong>Large, atypical lymphoid cells<\/strong>&nbsp;with granular cytoplasmic changes that can show a high proliferation rate and necrotizing cell destruction.<br>The cells show a&nbsp;<strong>pleomorphic cell morphology<\/strong>&nbsp;open, with frequent nuclear deformation and a hyperchromatic nucleus<\/li>\n\n\n\n<li><strong>Immunophenotype<\/strong><br>The tumor cells express&nbsp;<strong>CD56<\/strong>,&nbsp;<strong>CD2<\/strong>,&nbsp;<strong>CD3\u03b5 Cytotype<\/strong>,&nbsp;<strong>Granzyme B<\/strong>,&nbsp;<strong>TIA-1<\/strong>,&nbsp;<strong>Perforin<\/strong>&nbsp;and other cytotoxic molecules. They are&nbsp;<strong>CD3-, CD4-, CD8-, and CD5-negative<\/strong>, which deviates from T-cells<br>The expression of CD56 alone is not specific, but must be interpreted in the context of other NK markers.<\/li>\n\n\n\n<li><strong>Molecular Pathology<\/strong><br>In the&nbsp;<strong>In the vast majority of cases, the Epstein-Barr virus (EBV) is clonally present<\/strong>, demonstrable by means of&nbsp;<strong>EBER in situ hybridization<\/strong><br>Are found&nbsp;<strong>no clonal TCR gene rearrangements<\/strong>, which proves the NK cell lineage<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_-methodik-7\"><\/span>Differential diagnosis and methodology<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The diagnosis requires a&nbsp;<strong>multimodal analysis<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Clinical examination<\/strong><br>Differentiation of systemic inflammation, infections, and other hematological diseases<\/li>\n\n\n\n<li><strong>Blood count and bone marrow biopsy<\/strong><br>Detection of atypical lymphoid cells in peripheral blood and bone marrow<\/li>\n\n\n\n<li><strong>Immunophenotyping (Flow Cytometry)<\/strong><br>Confirmation of CD56+, CD2+, CD3\u03b5+, cytotoxic molecules+, and T-cell antigen-negative phenotype<\/li>\n\n\n\n<li><strong>Molecular pathology<\/strong>:&nbsp;<strong>EBER in situ hybridization<\/strong>&nbsp;for the detection of EBV<br><strong>PCR on clonal TCR rearrangements<\/strong>&nbsp;(usually negative)<\/li>\n\n\n\n<li><strong>Differential diagnoses<\/strong><br>- <strong>Nasal NK\/T-cell lymphoma<\/strong><br>Similar phenotype, but&nbsp;<strong>local localization (nose, nasopharynx)<\/strong><br>strong angio-centric growth<br><strong>also EBV+<\/strong><br>- <strong>Aggressive B-cell lymphomas<\/strong>&nbsp;(e.g., DLBCL)<br>CD20+, CD5-, CD10+<br><strong>no CD56+<\/strong>;&nbsp;<strong>No EBV+<\/strong><br>- <strong>T-cell lymphomas<\/strong><br>CD3+, CD4+, or CD8+<br><strong>Clonal TCR rearrangement<\/strong>;&nbsp;<strong>CD56- or weakly<\/strong><br>- <strong>Reactive lymphadenopathies<\/strong>&nbsp;(e.g., Kikuchi's disease):<br>Focal infiltrates, mass apoptosis,&nbsp;<strong>young Asian women<\/strong><br><strong>No EBV+<\/strong><br><strong>no systemic infestation<\/strong><br>- <strong>Myeloid Leukemias<\/strong><br><strong>CD3-<\/strong>,&nbsp;<strong>CD13\/CD33+<\/strong>,&nbsp;<strong>no CD56+<\/strong><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-25\"><\/span>Therapy<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Standard therapy<\/strong><br><strong>Intensive Chemotherapy<\/strong>&nbsp;(e.g., CHOP, Hyper-CVAD) in combination with&nbsp;<strong>anti-CD52 antibodies (Alemtuzumab)<\/strong>&nbsp;or&nbsp;<strong>anti-CD25 antibodies (Denileukin diftitox)<\/strong><\/li>\n\n\n\n<li><strong>Targeted therapies<\/strong><br><strong>BTK inhibitors (e.g., Ibrutinib)<\/strong>&nbsp;and&nbsp;<strong>PI3K inhibitors (e.g., Idelalisib)<\/strong>&nbsp;are effective in individual cases, especially in EBV-positive tumors<\/li>\n\n\n\n<li><strong>Allogeneic stem cell transplantation (SCT)<\/strong><br><strong>The only potentially curative therapy<\/strong>, especially in patients with good general condition and a suitable donor.<br>Indexed at&nbsp;<strong>First-line therapy failure or relapse<\/strong><\/li>\n\n\n\n<li><strong>Immunotherapy<\/strong><br><strong>NK cell-based cell therapies<\/strong>&nbsp;and&nbsp;<strong>CAR-NK cells<\/strong>&nbsp;evaluated in clinical trials<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-24\"><\/span>Forecast<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Very unfavorable<\/strong><br>The&nbsp;<strong>5-year survival rate is less than 20 %<\/strong>, especially in advanced stages.&nbsp;<\/li>\n\n\n\n<li><strong>Factors with an unfavorable prognosis<\/strong><br>- <strong>Systemic infestation<\/strong><br>- <strong>Bone marrow involvement<\/strong><br>- <strong>large tumor mass<\/strong><br>- <strong>EBV positivity<\/strong><br>- <strong>high proliferation rate<\/strong><\/li>\n\n\n\n<li><strong>Favorable prognostic factors<\/strong><br>- <strong>Early diagnosis<\/strong><br>- <strong>Good general condition<\/strong><br>. <strong>Reaction to chemotherapy<\/strong><br>- <strong>Success of allogeneic SCT<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The diagnosis and therapy require a&nbsp;<strong>interdisciplinary collaboration<\/strong>&nbsp;between hematologists, oncologists, pathologists, and molecular biology laboratories.<\/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>Hodgkin's lymphoma<\/strong> - Related diseases<\/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>Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The <strong>Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL)<\/strong>&nbsp;is a rare subtype of Hodgkin's lymphoma, accounting for about&nbsp;<strong>5\u201310 % of all Hodgkin lymphoma cases<\/strong>&nbsp;makes the difference.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">He is characterized by a&nbsp;<strong>cheap forecast<\/strong>, a&nbsp;<strong>Typical age of onset before age 40<\/strong>&nbsp;and a&nbsp;<strong>male prevalence of 3:1<\/strong>&nbsp;Australia.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_und_morphologisches_Bild-4\"><\/span><strong>Clinical and Morphological Picture<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Clinical features<\/strong><br>Often&nbsp;<strong>limited disease to peripheral lymph nodes<\/strong>&nbsp;(Neck, Armpit, Groin)<br>- <strong>Rare B-symptoms<\/strong>&nbsp;Fever, night sweats, weight loss<br>- <strong>Mediastinal involvement is rare<\/strong>, no spatially continuous spread<br>- <strong>More than 80 % of cases in Stage I or II<\/strong><br>\u2013 Extranodal involvement (spleen, liver, bone marrow, lung) occurs only in&nbsp;<strong>10\u201315 % (spleen), &lt;5 % (liver, bone marrow, lung)<\/strong>&nbsp;on<\/li>\n\n\n\n<li><strong>Morphological characteristics<\/strong><br>- <strong>No typical Hodgkin and Reed-Sternberg (HRS) cells<\/strong><br>- <strong>Malignant Lymphocyte Predominant (LP) cells<\/strong>&nbsp;\u2013 monoclonal B cells from the germinal center<br>- <strong>CD20-positive<\/strong>,&nbsp;<strong>CD15-negative<\/strong>,&nbsp;<strong>CD30-negative<\/strong>&nbsp;(differentiated from classical HL)<br>- <strong>Typical Growth Forms<\/strong><br>\u2013 \u2013 <strong>Knotty (nodular) shape (Pattern A)<\/strong> \u2013 Lower forecast<br>- <strong>\u2013 Diffuse (atypical) form (patterns C, E)<\/strong> \u2013 More frequent advanced stage, higher recurrence rate<br>- <strong>Angiogenesis<\/strong> \u2013 Low vascular density (MVD), diffuse vascular distribution<br>differs from classic HL and 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>Differential diagnosis and methodology<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The differential diagnosis is crucial, as NLPHL morphologically and immunophenotypically overlaps with other lymphomas:<\/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>Differential diagnosis<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Key features<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Distinguishing features<\/strong><\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Classic lymphocyte-rich HL (cHL)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">HRS cells, CD30+\/CD15+, CD20\u2013<\/td><td class=\"has-text-align-left\" data-align=\"left\">LP cells in NLPHL are CD20+ and CD30\u2013<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Progressive Transformation of Germinal Centers (PTGC)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Germinal center proliferation, CD20+ B cells<\/td><td class=\"has-text-align-left\" data-align=\"left\">No structural destruction, no LP cells; NLPHL shows characteristic nodular structures<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>T-cell\/histiocyte-rich large B-cell lymphoma (THRLBCL)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Aggressive growth, high T-cell\/histiocyte surplus<\/td><td class=\"has-text-align-left\" data-align=\"left\">Similar morphology to diffuse NLPHL;&nbsp;<strong>Differentiation solely by immunophenotype (CD20+ B cells) and molecular investigation (clonal B cell rearrangement)<\/strong><\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Follicular lymphoma (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\">No LP cells;&nbsp;<strong>No CD20+ LP cells<\/strong>, but rather uniform B-cell proliferation<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Angioimmunoblastic T-cell lymphoma (AITL)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">CD4+ T cells, HEV changes, CD10+ T cells<\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>CD20\u2013 in T cells<\/strong>,&nbsp;<strong>Clonal T-cell rearrangement<\/strong>; in contrast to NLPHL, which shows clonal B cells<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Follicular T-cell lymphoma (FTCL)<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">T-cell-based, CD4+<\/td><td class=\"has-text-align-left\" data-align=\"left\"><strong>Clonal T-cell rearrangement<\/strong>,&nbsp;<strong>no B-cell lineage<\/strong><\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostik-4\"><\/span>Diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Lymph node biopsy<\/strong><\/li>\n\n\n\n<li><strong>Immunohistochemistry<\/strong><br>CD20+, CD15\u2013, CD30\u2013, CD45+, BCL2+ (in LP cells)<\/li>\n\n\n\n<li><strong>Molecular biology<\/strong><br>Detection of clonal B-cell rearrangements (Ig genes)<\/li>\n\n\n\n<li><strong>Biopsy for recurrence<\/strong><br><strong>Mandatory<\/strong>, yes&nbsp;<strong>bis zu 10 % der Patienten eine Transformation in ein aggressives B-Zell-Lymphom (z.\u202fB.\u00a0\u00a0DLBCL)<\/strong>&nbsp;experience<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-26\"><\/span><strong>Therapy<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Early stage (IA without risk factors)<\/strong><br>- <strong>Irradiation of the affected area (IFRT)<\/strong>&nbsp;with 30\u201336 Gy<br>- <strong>Rituximab alone<\/strong>&nbsp;(Anti-CD20) as an alternative, radiation-free option in studies<\/li>\n\n\n\n<li><strong>Early stage (not IA or with risk factors)<\/strong><br>- <strong>Therapy analogous to classic HL<\/strong>Chemotherapy (e.g.&nbsp;<strong>ABVD<\/strong>Protocol<br>- <strong>B-cell NHL protocols<\/strong>&nbsp;(e.g.&nbsp;<strong>R-CHOP<\/strong>) can also be effective<\/li>\n\n\n\n<li><strong>Recurrence<\/strong><br>- <strong>Rituximab<\/strong>&nbsp;(Anti-CD20) is&nbsp;<strong>effective in relapsed NLPHL<\/strong><br>- <strong>High-dose chemotherapy + autologous stem cell transplantation<\/strong>&nbsp;only for&nbsp;<strong>few patients<\/strong>&nbsp;required<br>- <strong>Salvage therapies<\/strong>&nbsp;like ICE or according to cHL protocols<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-25\"><\/span><strong>Forecast<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Very cheap<\/strong><br>- <strong>10-year survival rate &gt;90 %<\/strong>&nbsp;(limited stadium)<br>- <strong>First-line treatment leads to remission in 90\u2013100 %<\/strong><br>- <strong>Recurrence in 10\u201315 %<\/strong>, mostly&nbsp;<strong>3\u20136 years after diagnosis<\/strong><\/li>\n\n\n\n<li><strong>Long-term consequences<\/strong><br>- <strong>Secondary malignancies<\/strong>&nbsp;e.g., diffuse large B-cell lymphoma \u2013&nbsp;<strong>25 % Risk after 20 years<\/strong>)<br>\u2013 Carcinomas (lung, breast, gastrointestinal tract) \u2013 often in irradiated regions<\/li>\n\n\n\n<li><strong>Long-term monitoring<\/strong>&nbsp;required<br>\u2013 Proof of secondary malignancies<br>Screening for cardiopulmonary diseases (caused by radiation therapy)<\/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>EBV-positive Diffuse Large B-cell Lymphoma (PTLD)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+ DLBCL) in the context of post-transplant lymphoproliferative disorder (PTLD) is a rare but potentially life-threatening complication after organ or stem cell transplantation.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It typically arises in patients with an immunosuppressed immune response who are unable to control Epstein-Barr virus (EBV)-infected B cells.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The incidence is higher in the first few years after transplantation, with a second peak in frequency occurring five to ten years later.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_und_morphologisches_Bild-5\"><\/span>Clinical and Morphological Picture<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Clinical picture<\/strong><br>The illness often manifests&nbsp;<strong>extranodal<\/strong>&nbsp;(e.g., in the gastrointestinal tract, lungs, skin, CNS), but can also occur nodularly<br>Symptoms are non-specific and include fever, night sweats, weight loss (B symptoms), as well as organ dysfunction depending on the location.<br>Systemic involvement is possible, especially in the primary cutaneous form.<\/li>\n\n\n\n<li><strong>Morphological characteristics<\/strong><br>- <strong>Diffuses, polymorphous lymphatic infiltrate<\/strong>&nbsp;with large, atypical B-cell blasts<br>\u2013 Common&nbsp;<strong>Hodgkin and Reed-Sternberg-like cells<\/strong>&nbsp;(HRS-like), necrosis and ulcerations<br>- <strong>CD30 positivity<\/strong>&nbsp;in about 10\u201320 % of cases,&nbsp;<strong>CD138-negative<\/strong>&nbsp;(distinguishes from plasma cell neoplasms)<br>- <strong>EBV latency type III<\/strong>&nbsp;with expression of EBNA-2, LMP1, and LMP2 \u2013 typical for PTLD<br>- <strong>Immunohistochemistry<\/strong><br>Positive for&nbsp;<strong>CD20, CD79a, PAX5, MUM1<\/strong><br>negative for CD5, CD10 (unlike GCB-DLBCL)<br>- <strong>Ki67 Index<\/strong><br>High (&gt;90 %), indicating rapid proliferation<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-21\"><\/span>Differential diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The differential diagnosis includes:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>EBV-negative DLBCL<\/strong><br>mostly in older adulthood, without immunosuppression<\/li>\n\n\n\n<li><strong>Primary cutaneous DLBCL<\/strong><br>localized to the skin, rarely systemic<\/li>\n\n\n\n<li><strong>EBV-positive mucocutaneous ulcer<\/strong><br>Self-limiting course, good response to conservative measures, no systemic growth<\/li>\n\n\n\n<li><strong>Primary cutaneous intravascular large B-cell lymphoma (PCIVLBL)<\/strong><br>Intra- and perivascular infiltrates, high morbidity due to thrombosis<\/li>\n\n\n\n<li><strong>Other forms of PTLD<\/strong><br>- <strong>Monomorphic PTLD<\/strong>&nbsp;(EBV-negative)<br>More frequent, monoclonal, less responsive to immunosuppression reduction<br>- <strong>Polyclonal PTLD<\/strong><br>Self-limiting, often responsive to reduction of immunosuppression<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostik-5\"><\/span>Diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Histology<\/strong><br>Lymph node or organ biopsy<\/li>\n\n\n\n<li><strong>Immunohistochemistry<\/strong><br>CD20, CD79a, MUM1, CD30, CD138<\/li>\n\n\n\n<li><strong>EBV Detection<\/strong><br><strong>In situ hybridization (ISH)<\/strong>&nbsp;for EBV-miRNA (EBER-ISH) \u2013&nbsp;<strong>imperatively necessary for confirmation<\/strong>.&nbsp;<\/li>\n\n\n\n<li><strong>FISH<\/strong><br>Exclusion of MYC\/BCL2\/BCL6 rearrangements (e.g., for DLBCL\/HGBL-MYC\/BCL2)<\/li>\n\n\n\n<li><strong>Molecular genetics<\/strong><br>PCR for EBV DNA in serum or tissue (quantification for monitoring)<\/li>\n\n\n\n<li><strong>Imaging<\/strong><br><strong>PET-CT<\/strong>&nbsp;for staging and therapy planning<\/li>\n\n\n\n<li><strong>Bone marrow biopsy<\/strong><br>In case of suspected systemic involvement<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-27\"><\/span>Therapy<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>First line<\/strong><br>- <strong>Reduction of immunosuppression<\/strong>&nbsp;(with stable organ function)<br>- <strong>Rituximab<\/strong>&nbsp;(anti-CD20 antibody) -&nbsp;<strong>effective for EBV+ PTLD<\/strong>, often alone or in combination<br>\u2013 In advanced stages:&nbsp;<strong>R-CHOP<\/strong>&nbsp;(Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone)<\/li>\n\n\n\n<li><strong>Second line<\/strong><br>- <strong>CAR T-cell therapy<\/strong>&nbsp;(e.g., Tisagenlecleucel, Axicabtagen-ciloleucel) in relapsed or refractory disease<br>- <strong>EBV-specific T-cell preparations<\/strong>&nbsp;(in specialized centers)<br>- <strong>Bispecific antibodies<\/strong>&nbsp;(e.g., Epcoritamab, Glofitamab)<\/li>\n\n\n\n<li><strong>High-dose chemotherapy with autologous stem cell transplant<\/strong><br>In selected patients with early recurrences<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-26\"><\/span>Forecast<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Inexpensive<\/strong>&nbsp;with early diagnosis and therapy<\/li>\n\n\n\n<li><strong>Unfavorable factors<\/strong><br>Altered &gt;60 years old, advanced stage (III\/IV), multiple extranodal locations<br><strong>Elevated LDH<\/strong>,&nbsp;<strong>No response rate to immunosuppression reduction<\/strong><\/li>\n\n\n\n<li><strong>Median survival<\/strong><br>After rituximab therapy, the median survival time is approximately&nbsp;<strong>8.7 months<\/strong>, with significant improvement through modern therapies<\/li>\n\n\n\n<li><strong>Prognosis for EBV+ PTLD<\/strong><br>in general better than in EBV-negative PTLD, especially regarding response to immunosuppression reduction and rituximab<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Detection and early therapy are crucial.&nbsp;<strong>Interdisciplinary tumor conference<\/strong>&nbsp;is recommended, especially in complex cases.<\/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>Immunoproliferative diseases &amp; borderline cases<\/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>MALT lymphomas<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>MALT lymphoma (mucosa-associated lymphoid tissue lymphoma)<\/strong>&nbsp;is a rare form of malignant non-Hodgkin lymphoma that arises from B-cells and typically develops in mucous membranes, especially in the stomach, lungs, lacrimal glands, thyroid, or salivary glands.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It is a&nbsp;<strong>indolent (slowly progressing)<\/strong>&nbsp;Lymphoma, which in about&nbsp;<strong>5 % of annually diagnosed non-Hodgkin lymphomas<\/strong>&nbsp;appearance. A crucial etiology is the&nbsp;<strong>Chronic immune stimulation<\/strong>&nbsp;through infections (e.g.&nbsp;<em>Helicobacter pylori<\/em>&nbsp;in the stomach) or autoimmune diseases (e.g., Sj\u00f6gren's syndrome, Hashimoto's thyroiditis).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In contrast, the&nbsp;<strong>Post-transplant lymphoproliferative disorder (PTLD)<\/strong>&nbsp;after a solid organ or allogeneic stem cell transplant and is closely related to a&nbsp;<strong>Epstein-Barr Virus (EBV) Infection<\/strong>&nbsp;connected.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">PTLD occurs&nbsp;<strong>0.5\u201312 %<\/strong>&nbsp;of transplant patients and shows a spectrum from early lesions to aggressive monomorphic lymphomas.&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>Clinical picture and morphological features<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>MALT lymphoma<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Clinical picture<\/strong><br>Symptoms are often non-specific:&nbsp;<strong>Fatigue, fever, weight loss, nausea, anemia<\/strong><br>Localized infestation causes organ symptoms&nbsp;<strong>Upper abdominal pain, reflux, stomach bleeding<\/strong>,&nbsp;<strong>Visual disturbances with lacrimal gland involvement<\/strong>,&nbsp;<strong>Respiratory tract infections with lung involvement<\/strong><br>B-symptoms (fever, night sweats, weight loss) are rare<br><strong>No lymphadenopathy<\/strong>&nbsp;is typical<\/li>\n\n\n\n<li><strong>Morphology<\/strong><br>Histologically, MALT lymphoma shows a&nbsp;<strong>polymorphous small cell infiltrate<\/strong>&nbsp;with reactive follicles populating the mantle zone and interfollicular region<br>Neoplastic B cells are&nbsp;<strong>CD20+, CD19+, CD22+<\/strong>, but&nbsp;<strong>CD5\u2013, CD10\u2013, CD23\u2013<\/strong><br>Common translocations such as&nbsp;<strong>t(11;18)(q21;q21)<\/strong>&nbsp;BIRC3-MALT1 fusion is prognostically relevant<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Post-transplant lymphoproliferative disorder (PTLD)<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Clinical picture<\/strong><br>PTLD can&nbsp;<strong>early<\/strong>&nbsp;(after 3\u20136 months) or&nbsp;<strong>late<\/strong>&nbsp;occur after several years<br>Symptoms depend on the infestation:&nbsp;<strong>Enlarged lymph nodes, hepatosplenomegaly, organ failure<\/strong>&nbsp;(e.g., kidney failure after kidney transplant)<br><strong>EBV-positive<\/strong>&nbsp;in over 90 % of early lesions, but often&nbsp;<strong>EBV-negative<\/strong>&nbsp;in monomorphic lymphomas<\/li>\n\n\n\n<li><strong>Morphology<\/strong><br>PTLD shows a spectrum:&nbsp;<strong>early lesions<\/strong>&nbsp;(polyclonal, EBV+),&nbsp;<strong>Polymorphic PTLD<\/strong>&nbsp;(oligoclonal, EBV\u00b1),&nbsp;<strong>monomorphic PTLD<\/strong>&nbsp;(monoclonal, often EBV\u2013)<br>Histologically, it often resembles a&nbsp;<strong>Diffuse large B-cell lymphoma (DLBCL)<\/strong><br>CD20+ and CD79a+; often&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>Differential diagnosis and diagnostics<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Differential diagnoses for MALT lymphoma<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Reactive lymphoproliferations (e.g., in&nbsp;<em>H. pylori<\/em>Gastritis<\/li>\n\n\n\n<li>Other non-Hodgkin lymphomas (DLBCL, follicular lymphoma)<\/li>\n\n\n\n<li>Infections (e.g.&nbsp;<em>H. pylori<\/em>,&nbsp;<em>Chlamydia psittaci<\/em>)<\/li>\n\n\n\n<li>Autoimmune diseases (e.g., Sj\u00f6gren's syndrome, lupus)&nbsp;<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Differential diagnoses for PTLD<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Reactive lymphadenopathy<\/li>\n\n\n\n<li>Chronic infections (e.g., EBV infection)<\/li>\n\n\n\n<li>Other lymphomas (e.g., DLBCL, Hodgkin lymphoma)<\/li>\n\n\n\n<li>Organ rejection<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Diagnostic Methodology<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Biopsy<\/strong>&nbsp;the affected localization (gold standard)<\/li>\n\n\n\n<li><strong>Histology, Immunophenotyping<\/strong><br>CD20, CD79a, CD5, CD10, CD23<\/li>\n\n\n\n<li><strong>PCR analysis of IgH rearrangement<\/strong><br>for clonal analysis<\/li>\n\n\n\n<li><strong>FISH\/Genetics<\/strong><br>on the proof obligation for translocations (t(11;18), t(14;18))<\/li>\n\n\n\n<li><strong>Imaging<\/strong><br>(CT, MRI, PET-CT) for staging<\/li>\n\n\n\n<li><strong>Bone marrow aspiration<\/strong><br>to exclude bone marrow involvement<\/li>\n\n\n\n<li><strong>EBV DNA PCR in serum<\/strong><br>for PTLD diagnosis and monitoring&nbsp;<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-28\"><\/span><strong>Therapy<\/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>MALT lymphoma<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>H. pylori-positive gastric lymphoma<\/strong>:&nbsp;<strong>Antibiotic therapy<\/strong>&nbsp;Eradication&nbsp;<strong>Regression<\/strong>&nbsp;of lymphoma<\/li>\n\n\n\n<li><strong>H. pylori-negative gastric lymphoma<\/strong>&nbsp;or&nbsp;<strong>Non-gastric MALT lymphoma<\/strong><br>- <strong>Radiotherapy<\/strong>&nbsp;(e.g., in conjunctival lymphoma)<br>- <strong>Chemotherapy<\/strong>Chlorambucil, Cyclophosphamide, Fludarabine<br>- <strong>Rituximab<\/strong>&nbsp;CD20 antibodies in advanced cases<\/li>\n\n\n\n<li><strong>Indolent course<\/strong>&nbsp;\u2192 Treatment often&nbsp;<strong>not necessary<\/strong>, if asymptomatic (\u201eObserve\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>Post-transplant lymphoproliferative disorder (PTLD)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>First line<\/strong><br><strong>Reduction of immunosuppression<\/strong>&nbsp;(Core therapy)<\/li>\n\n\n\n<li><strong>Monoclonal antibody<\/strong><br><strong>Rituximab<\/strong>&nbsp;(CD20) \u2013 alone or in combination<\/li>\n\n\n\n<li><strong>Chemotherapy<\/strong><br>in advanced or aggressive courses (e.g., CHOP)<\/li>\n\n\n\n<li><strong>Cytokines<\/strong><br>(e.g., Interferon-\u03b1) for specific forms<\/li>\n\n\n\n<li><strong>Surgical removal<\/strong><br>for localized lesions&nbsp;<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-27\"><\/span><strong>Forecast<\/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>MALT lymphoma<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Good prognosis<\/strong><br>The&nbsp;<strong>10-year survival rate<\/strong>&nbsp;in treated isolated lymphomas is approximately&nbsp;<strong>75 %<\/strong><br>Median survival &gt;10 years<br>The risk of transformation into aggressive DLBCL is low (approx. 5-10 %)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"PTLD\"><\/span>Post-transplant lymphoproliferative disorder<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>1-year survival rate<\/strong>&nbsp;is up to&nbsp;<strong>90 %<\/strong>&nbsp;with early detected and treated PTLD, depending on the stage and therapy<\/li>\n\n\n\n<li>Monomorphic PTLD have a poorer prognosis<\/li>\n\n\n\n<li>Long-term survival is threatened by immunosuppression and the risk of infection.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Zusammenfassung\"><\/span><strong>Summary<\/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\">Feature<\/td><td class=\"has-text-align-left\" data-align=\"left\">MALT lymphoma<\/td><td class=\"has-text-align-left\" data-align=\"left\">Post-transplant lymphoproliferative disorder<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Etiology<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Chronic infection (e.g.&nbsp;&nbsp;<em>H. pylori<\/em>), autoimmune<\/td><td class=\"has-text-align-left\" data-align=\"left\">EBV infection, immunosuppression<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Typical localization<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Stomach, lungs, eye adnexa, thyroid gland<\/td><td class=\"has-text-align-left\" data-align=\"left\">Lymph nodes, liver, small intestine, lungs<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>Clonality<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Monoclonal<\/td><td class=\"has-text-align-left\" data-align=\"left\">Oligo-\/polyclonal (early), monoclonal (late)<\/td><\/tr><tr><td class=\"has-text-align-left\" data-align=\"left\"><strong>EBV status<\/strong><\/td><td class=\"has-text-align-left\" data-align=\"left\">Rarely positive<\/td><td class=\"has-text-align-left\" data-align=\"left\">Mostly positive (early), often negative (late)<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Lymphomatoide_Granulomatose\"><\/span>Lymphomatoid granulomatosis<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The <strong>Lymphomatoid granulomatosis<\/strong>&nbsp;is a rare, angiocentric and destructive lymphoproliferative disease that belongs to the B-cell proliferative diseases with varying malignant potential.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It is called&nbsp;<strong>granulomatous systemic disease<\/strong>&nbsp;with a&nbsp;<strong>Epstein-Barr virus (EBV) association<\/strong>&nbsp;(detectable by LMP1 expression) and shows a&nbsp;<strong>CD20 and CD30 expression<\/strong>&nbsp;of the tumor cells.&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>Clinical picture and clinical-morphological features<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Skin manifestations<\/strong>&nbsp;occur at about&nbsp;<strong>45 % of the patients<\/strong>&nbsp;and are uncharacteristic:<br>- Painless&nbsp;<strong>reddish-brown spots, papules, plaques or nodules<\/strong><br>- Rare:&nbsp;<strong>Erythema nodosum-like nodules<\/strong>&nbsp;with a tendency to&nbsp;<strong>Ulceration<\/strong><br>- No epidermotropism<\/li>\n\n\n\n<li><strong>Extracutaneous organ involvement<\/strong><br>- <strong>lung<\/strong>Cough, shortness of breath, chest pain, fever, weight loss<br>- <strong>Central nervous system (CNS)<\/strong>: At approx.&nbsp;<strong>26 % of the patients<\/strong>&nbsp;- Headaches, ataxia, hemiplegia, cramps<br>- <strong>Liver and kidney<\/strong>Pathological laboratory values (e.g. elevated liver values, renal insufficiency)<\/li>\n\n\n\n<li><strong>General symptoms<\/strong>Fever, non-specific inflammatory phenomena, B-symptoms (weight loss, night sweats)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_-methodik-9\"><\/span><strong>Differential diagnosis and methodology<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The differential diagnosis is crucial, as the clinical picture is non-specific.<br>Main candidates:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Sarcoidosis<\/strong><br>Granulomatous processes, but&nbsp;<strong>No angiocentric destruction<\/strong>,&nbsp;<strong>no EBV association<\/strong>,&nbsp;<strong>No atypical lymphocytes<\/strong><\/li>\n\n\n\n<li><strong>B-cell lymphomas (especially diffuse large B-cell lymphoma)<\/strong><br>Monoclonal B-cell proliferation,&nbsp;<strong>Lack of granulomatous structures<\/strong>,&nbsp;<strong>higher blast rate<\/strong>&nbsp;(Grade III)<\/li>\n\n\n\n<li><strong>Wegener's granulomatosis (GPA)<\/strong><br><strong>Small vessel vasculitis<\/strong>,&nbsp;<strong>positive ANCA<\/strong>,&nbsp;<strong>non-EBV-associated<\/strong>,&nbsp;<strong>no CD20 expression<\/strong>&nbsp;of the cells<\/li>\n\n\n\n<li><strong>Cutaneous lymphomas<\/strong><br>Distinction by&nbsp;<strong>Epidermotropism<\/strong>&nbsp;(absent in lymphomatoid granulomatosis)<\/li>\n\n\n\n<li><strong>Eosinophilic myalgia syndrome<\/strong><br>No granulomatous infiltration, usually with eosinophilia and myalgia<\/li>\n\n\n\n<li><strong>Infectious granulomatoses<\/strong><br>(e.g. tuberculosis, histoplasmosis)<br>Detection of pathogens in the tissue.&nbsp;<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Diagnostic methods<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Skin and organ biopsy<\/strong>&nbsp;(lung, kidney) with histological analysis<\/li>\n\n\n\n<li><strong>Immunohistochemistry<\/strong><br>CD20+, CD30+, LMP1+ (EBV)<\/li>\n\n\n\n<li><strong>Molecular biological analysis<\/strong><br>EBV DNA detection in tissue<\/li>\n\n\n\n<li><strong>Imaging<\/strong><br>CT\/MRI (lung, CNS), PET-CT for staging and therapy monitoring (e.g. increased FDG uptake)<\/li>\n\n\n\n<li><strong>Laboratory<\/strong><br>Elevated inflammatory parameters (CRP, SED),&nbsp;<strong>positive EBV serology<\/strong>, elevated LDH<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-29\"><\/span><strong>Therapy<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">It exists&nbsp;<strong>No established therapy standard<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The therapy is based on the&nbsp;<strong>Histology stage<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Grade I<\/strong>&nbsp;(Low-Grade)<br>- <strong>Watchful Waiting<\/strong>&nbsp;with immunomodulation (e.g. improvement of the immune status), as spontaneous remissions are possible.<\/li>\n\n\n\n<li><strong>Grade II and III<\/strong>&nbsp;(high-grade) or multiple affected organs<br>- <strong>Combination therapy<\/strong>:&nbsp;<strong>CHOP scheme<\/strong>&nbsp;(cyclophosphamide, doxorubicin, vincristine, prednisone) or&nbsp;<strong>R-CHOP<\/strong>&nbsp;(with Rituximab)<br>- <strong>Immunosuppressive therapy<\/strong>&nbsp;to&nbsp;<strong>Fauci scheme<\/strong>&nbsp;(prednisone + cyclophosphamide)<br>- <strong>Aggressive therapy for recurrence or grade III<\/strong><br>\u2013 \u2013 <strong>High-dose chemotherapy<\/strong>&nbsp;(e.g. BEAM) +&nbsp;<strong>Autologous stem cell transplantation (ASCT)<\/strong><br>\u2013 \u2013 <strong>Radioimmunotherapy<\/strong>&nbsp;with&nbsp;<strong>Y-90-Ibritumomab-Tiuxetan<\/strong>&nbsp;in combination with ASCT (proven for recurrences)<br>\u2013 \u2013 <strong>Interferon-\u03b12b<\/strong>&nbsp;as an additional option (demonstrably effective in individual cases)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-28\"><\/span><strong>Forecast<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Variable course<\/strong><br>Possible&nbsp;<strong>Spontaneous remissions<\/strong>but also&nbsp;<strong>rapid progression<\/strong><\/li>\n\n\n\n<li><strong>Frequent complication<\/strong><br>Development of a&nbsp;<strong>aggressive B-cell lymphoma<\/strong>&nbsp;(e.g. diffuse large B-cell lymphoma)<\/li>\n\n\n\n<li><strong>Cause of death<\/strong><br>Most&nbsp;<strong>respiratory insufficiency<\/strong>&nbsp;or&nbsp;<strong>septic complications<\/strong><\/li>\n\n\n\n<li><strong>Long-term survival rate<\/strong><br>Approx.&nbsp;<strong>25 %<\/strong>&nbsp;(depending on severity and response to therapy)<\/li>\n\n\n\n<li><strong>Prognostic factors<\/strong><br>Stage, organ involvement (especially CNS), EBV load, LDH values.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">One&nbsp;<strong>Early histological confirmation<\/strong>&nbsp;and&nbsp;<strong>multimodal therapy<\/strong>&nbsp;are decisive for the prognosis.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Skin biopsies<\/strong>&nbsp;can provide the decisive clue, but&nbsp;<strong>Systemic participation<\/strong>&nbsp;must always be clarified.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"GANZL\"><span class=\"ez-toc-section\" id=\"Granulomatose_mit_organerhaltender_Vaskulitis_GANZL\"><\/span>Granulomatosis with organ-preserving vasculitis (GANZL)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Granulomatosis with polyangiitis (GPA), formerly known as Wegener's disease, is a rare, systemic, necrotizing small vessel vasculitis characterized by a&nbsp;<strong>Extravascular granulomatous inflammation<\/strong>&nbsp;in the respiratory tract and a&nbsp;<strong>Vasculitis of small and medium-sized vessels<\/strong>&nbsp;is marked.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It belongs to the ANCA-associated vasculitides (AAV) and is typically associated with&nbsp;<strong>PR3-ANCA<\/strong>&nbsp;associated.&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>Clinical picture and clinical-morphological features<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The clinical picture varies depending on the involvement of the organs, with the&nbsp;<strong>pulmonary-renal syndrome<\/strong>&nbsp;(alveolar hemorrhage, rapidly progressive glomerulonephritis) and the&nbsp;<strong>Involvement of the upper respiratory tract<\/strong>&nbsp;are typical.&nbsp;<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Upper respiratory tract<\/strong><br>Recurrent bloody rhinitis, nosebleeds, nasal crusts, mucous membrane appears granulated,&nbsp;<strong>Saddle nose<\/strong>&nbsp;(nasal bridge collapse), sinusitis, subglottic stenosis<\/li>\n\n\n\n<li><strong>Lower respiratory tract<\/strong><br>Cough, hemoptysis, pulmonary nodules with cavitation, interstitial lung changes, alveolar hemorrhage (acute dyspnea, blood in sputum)<\/li>\n\n\n\n<li><strong>Kidneys<\/strong><br>Glomerulonephritis with focal necrotizing glomerulonephritis, often with crescent formation, hypertension, edema, elevated serum creatinine<\/li>\n\n\n\n<li><strong>skin<\/strong><br>Palpable purpura, subcutaneous nodules, pyoderma gangraenosum<\/li>\n\n\n\n<li><strong>Nervous system<\/strong><br>Mononeuritis multiplex, cranial nerve palsies<\/li>\n\n\n\n<li><strong>Eyes<\/strong><br>Conjunctivitis, scleritis, uveitis, retro-orbital infiltrates (exophthalmos, visual disturbances)<\/li>\n\n\n\n<li><strong>Other organs<\/strong><br>Heart (rarely coronary involvement), joints (non-erosive arthritis), liver, spleen<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Histologically, the biopsy shows a&nbsp;<strong>Necrotizing vasculitis of small and medium-sized vessels<\/strong>, granulomatous inflammation with epithelioid cells, giant cells and&nbsp;<strong>geographic necrosis<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">However, the classic triad (granulomatous inflammation, necrotizing vasculitis, geographic necrosis) is not present in the&nbsp;<strong>localized GPA<\/strong>&nbsp;rarely detectable.&nbsp;<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnose_und_-methodik\"><\/span>Differential diagnosis and methodology<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The diagnosis requires a differentiated clarification, as many diseases have similar symptoms.&nbsp;<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Clinical symptoms<\/strong><br>(e.g. nosebleeds, pulmonary nodules, glomerulonephritis) must be differentiated from other causes<\/li>\n\n\n\n<li><strong>Serological tests<\/strong>: Proof of&nbsp;<strong>PR3-ANCA<\/strong>&nbsp;(specific for GPA) or MPO-ANCA (for MPA\/EGPA)<br>ANCA positivity is not 100 % certain, as ANCA-negative cases also occur<\/li>\n\n\n\n<li><strong>Biopsy<\/strong><br><strong>Tissue samples from affected organs<\/strong> (e.g. nose, lung, kidney) are the gold standard for confirming the diagnosis.<br>Histologically detectable: necrotizing vasculitis, granulomatous inflammation<\/li>\n\n\n\n<li><strong>Imaging procedures<\/strong><br>CT of the thorax (lung nodules, cavitation), MRI (e.g. brain, nerves), ultrasound (kidneys)<\/li>\n\n\n\n<li><strong>Cerebrospinal fluid examination<\/strong><br>In case of neurological symptoms: increased cell count and protein (inflammatory CSF), but no oligoclonal bands<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Differential diagnoses<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Infections<\/strong><br>Tuberculosis, fungal infections (e.g. aspergillosis), bacterial endocarditis<\/li>\n\n\n\n<li><strong>Other vasculitides<\/strong><br>Giant cell arteritis, Takayasu's arteritis, polyarteritis nodosa<\/li>\n\n\n\n<li><strong>Autoimmune diseases<\/strong><br>Systemic lupus erythematosus (SLE), Sj\u00f6gren's syndrome<\/li>\n\n\n\n<li><strong>Tumors<\/strong><br>Lymphoma, carcinoma (especially pulmonary)<\/li>\n\n\n\n<li><strong>Infectious granulomas<\/strong><br>Tuberculosis, sarcoidosis<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-30\"><\/span>Therapy<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The therapy depends on the severity and organ involvement and is divided into&nbsp;<strong>Remission induction<\/strong>&nbsp;and&nbsp;<strong>Maintenance of remission<\/strong>.<br><br><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Remission induction<\/strong>&nbsp;(in case of serious illness)<br>- <strong>Rituximab<\/strong>&nbsp;(anti-CD20 antibody) or&nbsp;<strong>Cyclophosphamide<\/strong>&nbsp;(in combination with&nbsp;<strong>Glucocorticoids<\/strong>, e.g. prednisone)<br>- In severe alveolar hemorrhage or rapid progressive glomerulonephritis:&nbsp;<strong>Plasma exchange<\/strong><\/li>\n\n\n\n<li><strong>Maintenance of remission<\/strong><br>- <strong>Azathioprine<\/strong>&nbsp;or&nbsp;<strong>Methotrexate<\/strong>&nbsp;(effective)<br>- <strong>Mycophenolate mofetil<\/strong>&nbsp;(less effective)<br>- <strong>Rituximab<\/strong>&nbsp;also for maintenance therapy (for PR3-ANCA-positive patients)<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-29\"><\/span>Forecast<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li>With modern therapies, the following can be achieved&nbsp;<strong>more than 80 % of patients achieve remission<\/strong><\/li>\n\n\n\n<li><strong>Recurrences are frequent<\/strong>, especially with PR3-ANCA positivity, pulmonary involvement or involvement of the upper respiratory tract<\/li>\n\n\n\n<li><strong>Prognostic factors for poor outcome<\/strong><br>- Poor kidney function at the time of diagnosis (e.g. need for dialysis)<br>- High disease activity (Birmingham Vasculitis Activity Score)<br>- Cardiac or gastrointestinal manifestations<br>- Age &gt;65 years<br>- Sclerosing glomerulonephritis in the biopsy<\/li>\n\n\n\n<li><strong>Mortality<\/strong><br>is increased, especially with severe kidney involvement or infections (therapy-associated)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">GPA is a complex, multi-organ disease whose diagnosis is based on a combination of clinical presentation, ANCA serology and&nbsp;<strong>biopsy-confirmed histological change<\/strong>&nbsp;is based on.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Early, centralized therapy with immunosuppressants is crucial for a favorable prognosis.<\/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>EBV-associated B-cell lymphoproliferations<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Epstein-Barr virus (EBV)-associated B-cell lymphoproliferations comprise a spectrum of diseases that differ in their biology, clinical manifestation and prognosis.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A differentiated differentiation is crucial for the treatment decision.&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>Clinical picture and morphological features<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Post-transplant lymphoproliferative diseases (PTLD)<\/strong><br>Occurs after solid organ or hematopoietic stem cell transplantation. The clinical picture depends on the stage of the disease:<br>- <strong>Early lesions (approx. 5%)<\/strong><br>Oligo- or polyclonal,&nbsp;<strong>almost always EBV-positive<\/strong>, often with monoclonal B-cell expansion. Morphologically, they show diffuse infiltrative lymphocyte proliferation with cellular atypia<br>- <strong>Poly- and monomorphic PTLD<\/strong><br>\u2013 \u2013 <em>Polyclonal PTLD<\/em>:&nbsp;<strong>EBV-positive or -negative<\/strong>, often with polyclonal B-cell proliferation<br>\u2013 \u2013 <em>Monomorphic PTLD<\/em>:&nbsp;<strong>often EBV-negative<\/strong>&nbsp;(up to 50%), monoclonal, morphologically similar to a&nbsp;<strong>diffuse large B-cell lymphoma (DLBCL)<\/strong>, often with immunoblastic or anaplastic morphology<\/li>\n\n\n\n<li><strong>Epstein-Barr virus-positive DLBCL in older people<\/strong><br>- Mainly meets&nbsp;<strong>older adults<\/strong>&nbsp;(mostly &gt;60 years), often&nbsp;<strong>not immunosuppressed<\/strong><br>- Clinical<br>\u2013 \u2013 <strong>Extranodal manifestations<\/strong>&nbsp;(e.g. skin, gastrointestinal tract, CNS)<br>\u2013 \u2013 <strong>B symptoms<\/strong>&nbsp;Fever, night sweats, weight loss<br>\u2013 \u2013 <strong>Rapid progression<\/strong><br>- Morphology<br>\u2013 \u2013 <strong>Diffuse large cell population<\/strong>&nbsp;with centroblastic or immunoblastic atypia<br>\u2013 \u2013 <strong>high proliferation rate<\/strong>&nbsp;(Ki67 &gt;90%)<\/li>\n\n\n\n<li><strong>Aggressive primary cutaneous B-cell lymphoma (primary cutaneous DLBCL, lower extremity)<\/strong><br>- <strong>Extralymphatic infestation<\/strong>&nbsp;(skin, especially legs), mostly&nbsp;<strong>non-systemic<\/strong>, often&nbsp;<strong>only a single stove<\/strong><br>- <strong>EBV-positive<\/strong>&nbsp;in elderly patients,&nbsp;<strong>EBV-negative<\/strong>&nbsp;for younger<br>- Morphology<br>\u2013 \u2013 <strong>diffuse large B-cell proliferation<\/strong>&nbsp;with expression of cell types (e.g. immunoblastic)<\/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>Differential Diagnosis and Methodology<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cytomorphology<\/strong><br>- <strong>DLBCL, NOS<\/strong>&nbsp;vs.&nbsp;<strong>EBV+ DLBCL<\/strong><br>Morphology alone is not enough to differentiate<br>- <strong>PTLD vs. DLBCL<\/strong><br>Clinic (transplant history), clonality (PCR), EBV status (EBER-ISH) are decisive<\/li>\n\n\n\n<li><strong>Immunophenotyping<\/strong><br>- <strong>All EBV-associated lymphomas<\/strong><br>\u2013 \u2013 <strong>CD20+<\/strong>,&nbsp;<strong>CD79a+<\/strong>,&nbsp;<strong>PAX5+<\/strong>,&nbsp;<strong>CD45+<\/strong>,&nbsp;<strong>CD10+<\/strong>&nbsp;(for GCB subtype)<br>\u2013 \u2013 <strong>BCL6+<\/strong>,&nbsp;<strong>CD30+<\/strong>&nbsp;(for 10-20% of cases)<br>- <strong>EBV+ DLBCL in the elderly<\/strong><br>\u2013 \u2013 <strong>CD30+<\/strong>&nbsp;in up to 70% of cases<br>\u2013 \u2013 <strong>CD5-<\/strong>,&nbsp;<strong>CD138-<\/strong>,&nbsp;<strong>MYC-<\/strong>&nbsp;(not double-expresser)<\/li>\n\n\n\n<li><strong>Genetic and molecular biological methods<\/strong><br>- <strong>EBER-ISH (Epstein-Barr virus-encoded RNA in situ hybridization)<\/strong>,<strong> EBV detection<\/strong>&nbsp;in cells<br>- <strong>FISH<\/strong><br>Exclusion of&nbsp;<strong>MYC\/BCL2 translocations<\/strong>&nbsp;(then:&nbsp;<strong>Double-hit lymphoma<\/strong>)<br>- <strong>PCR for EBV DNA<\/strong><br>Quantification in serum\/plasma (not for diagnosis alone, but for monitoring)<br>- <strong>Gene expression analysis (COO subtype)<\/strong><br>\u2013 \u2013 <strong>GCB subtype<\/strong>&nbsp;(germinal center B-cell) - more common with&nbsp;<strong>EBV+ DLBCL in the elderly<\/strong><br>\u2013 \u2013 <strong>ABC subtype<\/strong>&nbsp;(activated B-cell) - more common in&nbsp;<strong>Post-transplant lymphoproliferative disorder<\/strong><\/li>\n\n\n\n<li><strong>Differential diagnosis<\/strong><br>- <strong>DLBCL, NOS<\/strong>Without EBV association, often with MYC\/BCL2 translocations<br>- <strong>Burkitt's lymphoma<\/strong><br>\u2013 \u2013 <strong>Extremely high proliferation rate (Ki67 &gt;95%)<\/strong>,&nbsp;<strong>MYC translocation<\/strong>,&nbsp;<strong>\u201estarry sky\u201c pattern<\/strong>,&nbsp;<strong>CD10+<\/strong>,&nbsp;<strong>BCL6+<\/strong>,&nbsp;<strong>CD5-<\/strong><br>- <strong>Anaplastic large cell lymphoma (ALCL)<\/strong><br>\u2013 \u2013 <strong>CD30+<\/strong>,&nbsp;<strong>ALK+<\/strong>&nbsp;(for ALK-positive ALCL),&nbsp;<strong>CD15+<\/strong>,&nbsp;<strong>T-cell phenotype<\/strong><br>- <strong>Hodgkin's lymphoma<\/strong><br>\u2013 \u2013 <strong>CD15+<\/strong>,&nbsp;<strong>CD30+<\/strong>,&nbsp;<strong>CD20-<\/strong>,&nbsp;<strong>CD45-<\/strong>,&nbsp;<strong>Reed-Sternberg cells<\/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>Therapy<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Post-transplant lymphoproliferative disorder<\/strong><br>- <strong>First line<\/strong><br>\u2013 \u2013 <strong>Reduction of immunosuppression<\/strong>&nbsp;(if possible)<br>\u2013 \u2013 <strong>Rituximab (monoclonal)<\/strong>, <strong>First choice<\/strong>&nbsp;for EBV+ PTLD<br>\u2013 \u2013 <strong>Advanced stage<\/strong><br>\u2013 \u2013 \u2013 <strong>R-CHOP<\/strong>&nbsp;or&nbsp;<strong>R-CHOP-like regimes<\/strong><br>\u2013 \u2013 <strong>For non-responsive cases<\/strong><br>\u2013 \u2013 \u2013 <strong>Chemotherapy<\/strong>,&nbsp;<strong>Cell therapy (e.g. CAR-T cells)<\/strong>.<\/li>\n\n\n\n<li><strong>EBV+ DLBCL in the elderly<\/strong><br>- <strong>R-CHOP<\/strong>&nbsp;(Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone)<br>- For patients with&nbsp;<strong>high risk (e.g. IPI high)<\/strong> <strong>Intensified therapy (e.g. DA-EPOCH-R)<\/strong><br>- <strong>CAR-T cells<\/strong>&nbsp;in case of recurrence\/refractory disease<\/li>\n\n\n\n<li><strong>Primary cutaneous DLBCL, lower extremity<\/strong><br>- <strong>Local therapy (radiation)<\/strong>&nbsp;With limited infestation<br>- <strong>Systemic therapy (R-CHOP)<\/strong>&nbsp;for multiple or systemic lesions<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\" id=\"prognose\"><span class=\"ez-toc-section\" id=\"Prognose-30\"><\/span><strong>Forecast<\/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>Post-transplant lymphoproliferative disorder<span class=\"ez-toc-section-end\"><\/span><\/h5>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Inexpensive<\/strong>&nbsp;with early diagnosis and reduction of immunosuppression<\/li>\n\n\n\n<li><strong>5-year survival rate<\/strong>: approx.&nbsp;<strong>60\u201370%<\/strong>, depending on the stage and response to therapy<\/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 in the elderly<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h5>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Worse forecast<\/strong>&nbsp;compared to EBV-negative DLBCL (especially in older patients).&nbsp;<\/li>\n\n\n\n<li><strong>5-year survival rate<\/strong>: approx.&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>Primary cutaneous DLBCL, lower extremity<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h5>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>More favorable forecast<\/strong>, if locally limited<\/li>\n\n\n\n<li><strong>5-year survival rate<\/strong>&gt;80% with local therapy<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The differential diagnosis of EBV-associated B-cell lymphoma requires multimodal diagnostics (histology, immunophenotype, EBER-ISH, FISH, gene expression analysis).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Therapy is based on the clinic, stage classification and risk profile, with rituximab and R-CHOP being central therapy components.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The prognosis varies greatly depending on the subtype and is generally less favorable compared to EBV-negative DLBCL, especially in older patients.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Hodgkin-Lymphom\"><\/span><strong>Hodgkin's lymphoma<\/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>Classical Hodgkin's lymphoma, nodular sclerosis (cHL, NS)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Classical Hodgkin's lymphoma (cHL) with nodular sclerosis is the&nbsp;<strong>most common subtype<\/strong>&nbsp;of cHL, with a prevalence of about&nbsp;<strong>70 %<\/strong>&nbsp;in western countries.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It shows a&nbsp;<strong>bimodal age distribution<\/strong>&nbsp;with a peak occurrence between the ages of 20 and 30 and a second peak after the age of 65.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild-4\"><\/span>Clinical picture<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Symptomatology<\/strong><br>Painless enlargement of lymph nodes, often in the neck and cervical region, supraclavicular and in the mediastinum.<br>One&nbsp;<strong>B-symptomatics<\/strong>&nbsp;(fever, night sweats, weight loss &gt;10 %) is present in about 50 % of patients.<\/li>\n\n\n\n<li><strong>Localization<\/strong><br>Preferential infestation of&nbsp;<strong>mediastinal lymph nodes<\/strong>, which leads to a typical mediastinal tumor mass (in about 80 % of cases).<\/li>\n\n\n\n<li><strong>Laboratory findings<\/strong><br>Anemia and\/or pruritus occur in about a quarter of patients.&nbsp;<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisch-morphologische_Merkmale-9\"><\/span>Clinical-morphological features<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Histology<\/strong><br>Characterized by a&nbsp;<strong>nodular growth pattern<\/strong>,&nbsp;<strong>pronounced sclerosis<\/strong>&nbsp;(collagenous connective tissue strands) and&nbsp;<strong>Lacunar cells<\/strong>&nbsp;(a special form of Hodgkin-Reed-Sternberg cells that show an optically empty cytoplasm during formalin fixation)<\/li>\n\n\n\n<li><strong>Cell population<\/strong><br>Only about&nbsp;<strong>1 % of the cells<\/strong>&nbsp;are malignant tumor cells (Hodgkin-Reed-Sternberg cells). The remainder consists of a&nbsp;<strong>mixed infiltrate<\/strong>&nbsp;reactive cells: Lymphocytes, plasma cells, eosinophil granulocytes and histiocytes<\/li>\n\n\n\n<li><strong>Immunophenotype of the tumor cells<\/strong><br>- <strong>CD30+<\/strong>,&nbsp;<strong>CD15+<\/strong>,&nbsp;<strong>PD-L1+<\/strong>,&nbsp;<strong>MUM1+<\/strong><br>- <strong>CD20-\/+<\/strong>&nbsp;(positive in approx. 20 %),&nbsp;<strong>CD45-<\/strong><br>- <strong>EBV-<\/strong>&nbsp;or&nbsp;<strong>EBV+<\/strong>&nbsp;(in variable numbers)<br>- <strong>J-chain<\/strong><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik-22\"><\/span>Differential diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The differential diagnosis is crucial because of the clinical and histological similarity with other diseases:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Infectious mononucleosis<\/strong>&nbsp;(EBV-associated)<br>Differentiation by clinical picture, serological findings (heterophilic antibodies), and lack of clonal cell population<\/li>\n\n\n\n<li><strong>Follicular lymphoma<\/strong><br>Differentiation by lack of Reed-Sternberg cells, typical follicular growth pattern and CD10+\/CD20+\/BCL2+ immunophenotype<\/li>\n\n\n\n<li><strong>Lymphocyte-predominant Hodgkin's lymphoma (NLPHL)<\/strong><br>Differentiation by lack of CD30\/CD15 expression, positive CD20\/CD45\/J-chain expression and typical L&amp;H cells (lymphocyte- and histiocyte-rich cells)<\/li>\n\n\n\n<li><strong>Aggressive T-cell histiocyte-rich large B-cell lymphoma (TCHRBCL)<\/strong><br>Differentiation due to lack of CD30\/CD15 expression in tumor cells and other immunophenotypes (e.g. CD5+, CD10-)<\/li>\n\n\n\n<li><strong>Reactive germinal center progression (PTKZ)<\/strong><br>Differentiation by lack of clonal cell population and lack of typical HRS cells<\/li>\n\n\n\n<li><strong>EBV-associated diseases<\/strong>&nbsp;(e.g. EBV-positive mucocutaneous ulcer)<br>Differentiation by clinical picture, localization and EBV DNA detection<\/li>\n\n\n\n<li><strong>Anaplastic large cell lymphoma (ALK-negative)<\/strong><br>In lymphocyte-poor cHL, especially in HIV-positive patients, differentiation is necessary<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostik-6\"><\/span>Diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Biopsy<\/strong><br>Primary diagnosis by lymph node biopsy (usually mediastinal or cervical)<\/li>\n\n\n\n<li><strong>Immunohistochemistry<\/strong><br>Crucial for confirmation of the immunophenotype (CD30, CD15, CD20, CD45, PD-L1).<\/li>\n\n\n\n<li><strong>Imaging<\/strong><br>Computed tomography (CT) of the thorax, neck, abdomen and pelvis; positron emission tomography (PET) for staging and therapy monitoring<\/li>\n\n\n\n<li><strong>Bone marrow biopsy<\/strong><br>Only indicated for B symptoms or abnormal laboratory values<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-32\"><\/span>Therapy<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>Stage-adapted therapy<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Stage I\/II without risk factors<\/strong><br>Combined radio- and chemotherapy (e.g. ABVD + Involved Field Radiotherapy)<\/li>\n\n\n\n<li><strong>Stage I\/II with risk factors or stage III\/IV<\/strong><br>Chemotherapy (e.g. ABVD) with or without radiotherapy<\/li>\n\n\n\n<li><strong>New therapies<\/strong><br>Anti-CD30 antibody-cytostatic conjugates (e.g. brentuximab vedotin) in salvage therapy<\/li>\n\n\n\n<li><strong>Goal<\/strong><br>Long-term survival of&nbsp;<strong>80-90 %<\/strong>&nbsp;with adequate therapy<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-31\"><\/span>Forecast<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Without treatment&nbsp;<strong>moderately aggressive<\/strong><\/li>\n\n\n\n<li>With treatment&nbsp;<strong>extremely favorable<\/strong>, about&nbsp;<strong>80 % of the patients<\/strong>&nbsp;are cured in the long term<\/li>\n\n\n\n<li>The&nbsp;<strong>Histological subclassification (e.g. nodular sclerosis)<\/strong>&nbsp;has&nbsp;<strong>No therapeutic relevance<\/strong>&nbsp;today's therapy is adapted to the stage and risk of the disease.&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>Notice<\/strong>: The differential diagnosis requires a&nbsp;<strong>Multidisciplinary clarification<\/strong>&nbsp;by pathology, hematology and oncology.  The&nbsp;<strong>Early and correct diagnosis<\/strong>&nbsp;is crucial for successful therapy.<\/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>Classical Hodgkin's lymphoma (cHL) - mixed cellularity (MC)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>classical Hodgkin's lymphoma (cHL), mixed cellularity (MC)<\/strong>, is a histologic subtype of cHL, which is approximately&nbsp;<strong>25 % of cases<\/strong>&nbsp;and is particularly common in patients over the age of 50 and in HIV-positive people. Men are more frequently affected than women.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild_und_morphologische_Merkmale-4\"><\/span><strong>Clinical picture and morphological features<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Clinical<\/strong><br>Infestation preferred&nbsp;<strong>Cervical and abdominal lymph node regions<\/strong><br>Compared to other cHL subtypes, the mixed type is diagnosed more frequently in a&nbsp;<strong>advanced stage<\/strong>&nbsp;discovered and shows frequent&nbsp;<strong>B-symptomatics<\/strong>&nbsp;(fever, night sweats, weight loss &gt;10 % within 6 months)<\/li>\n\n\n\n<li><strong>Morphological<\/strong><br>- Characteristic is a&nbsp;<strong>Mixed cell infiltrate<\/strong>&nbsp;from Hodgkin and Reed-Sternberg cells (H-RS cells), lymphocytes, histiocytes, granulocytes (especially eosinophils) and fine fibrillar fibrosis<br>- H-RS cells are&nbsp;<strong>multinucleated (Reed-Sternberg cells)<\/strong>&nbsp;or mononuclear, with&nbsp;<strong>prominent nucleoli (\u201eowl's eye cells\u201c)<\/strong>&nbsp;and basophilic cytoplasm<br>- The tumor cells only make up about&nbsp;<strong>0.1-10 %<\/strong>&nbsp;of the total cell mass; the rest consists of reactive inflammatory infiltrate<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnose_und_-methodik-2\"><\/span><strong>Differential diagnosis and methodology<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Differential diagnosis is crucial, as cHL must be differentiated by its characteristic biphasic pattern (few tumor cells, strong reactive infiltrate) and specific immunophenotypes.&nbsp;<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Important differential diagnoses<\/strong><br>- <strong>Follicular lymphoma (FL)<\/strong><br>Neoplastic proliferation of centrocytes\/centroblasts with typical germinal center architecture, CD10+, bcl-2+, t(14;18)<br>- <strong>Diffuse large B-cell lymphoma (DLBCL)<\/strong>Diffuse infiltration of large, transformed B cells, CD20+, BCL6+, MUM1+, more frequently with B symptoms and rapid growth<br>- <strong>Chronic lymphocytic leukemia (CLL)<\/strong>Peripheral lymphadenopathy, bone marrow involvement, CD5+, CD23+, CD20 (weak), CD10-<br>- <strong>Mantle cell lymphoma (MCL)<\/strong>CD5+, CD23-, CD10-, t(11;14), mostly advanced at diagnosis, poor prognosis<br>- <strong>Multiple myeloma<\/strong>Bone pain, pathological fractures, plasma cell infiltration in the bone marrow, anemia, hypercalcemia<br>- <strong>Reactive lymphadenopathy<\/strong>No clonal proliferation, typically after infections, with normal architecture and lack of H-RS cells<\/li>\n\n\n\n<li><strong>Diagnostic Methodology<\/strong><br>- <strong>Histology<\/strong><br>Microscopic examination of the lymph node preparation with detection of H-RS cells and reactive infiltrate<br>- <strong>Immunohistochemistry<\/strong><br><strong>H-RS cells are positive for CD30, CD15, MUM1, PD-L1<\/strong>&nbsp;and mostly negative for CD45, CD20 (positive in approx. 20 %), J-chain, and BOB.1\/Oct2 (negative in classic HL)<br>- <strong>Molecular pathology<\/strong><br>Detection of clonal B-cell neoplasia (e.g. by immunoglobulin gene PCR, mutations)<br>- <strong>Imaging<\/strong><br>CT\/MRI for staging (Ann Arbor classification), PET-CT for therapy planning and monitoring<br>- <strong>Bone marrow biopsy<\/strong><br>For B symptoms or advanced stage to rule out bone marrow involvement<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie_und_Prognose-7\"><\/span><strong>Therapy and prognosis<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Therapy principle<\/strong><br><strong>Stage-adapted polychemotherapy<\/strong>&nbsp;(e.g. ABVD: doxorubicin, bleomycin, vinblastine, dacarbazine) combined with&nbsp;<strong>Radiotherapy<\/strong>&nbsp;For localized infestation (stages I-II)<\/li>\n\n\n\n<li><strong>Forecast<\/strong><br>Achieve with modern therapies&nbsp;<strong>over 80 % of patients achieve a long-term cure<\/strong><br>The 5-year survival rate is between&nbsp;<strong>75 % and 99 %<\/strong>, depending on the stage and risk factors<\/li>\n\n\n\n<li><strong>Prognostic factors<\/strong><br>B symptoms, high LDH, age &gt;50 years, extent of the disease (stage IV), number of affected lymph node regions<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The classic Hodgkin's lymphoma, mixed cellularity, is a&nbsp;<strong>Well treatable but complex disease<\/strong>, whose diagnosis and therapy are based on a&nbsp;<strong>multimodal, individualized approach<\/strong>&nbsp;based.<\/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>Classical Hodgkin's lymphoma - lymphocyte-rich type (cHL, LR)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>Lymphocyte-rich classical Hodgkin's lymphoma (cHL, LR)<\/strong>&nbsp;is a rare histologic variant of classic Hodgkin's lymphoma, which occurs in about&nbsp;<strong>4 %<\/strong>&nbsp;of all cases.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Through a&nbsp;<strong>Dominant lymphocyte-rich environment<\/strong>&nbsp;characterized by only a few Hodgkin and Reed-Sternberg cells (H-RS cells), which are typically&nbsp;<strong>CD30- and CD15-positive<\/strong>&nbsp;are.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The tumor cells often also carry&nbsp;<strong>CD20<\/strong>&nbsp;and&nbsp;<strong>CD23<\/strong>, but are&nbsp;<strong>CD30-negative<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The disease occurs more frequently in&nbsp;<strong>male patients around the age of 30<\/strong>&nbsp;and has a&nbsp;<strong>Very good forecast<\/strong>&nbsp;on.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild_und_morphologische_Merkmale-5\"><\/span>Clinical picture and morphological features<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Clinical picture<\/strong><br>The LR type usually manifests itself as&nbsp;<strong>Infestation of peripheral lymph nodes<\/strong>, often in the&nbsp;<strong>Cervical or axillary region<\/strong><br>Patients often show&nbsp;<strong>painless swelling of the lymph nodes<\/strong>, that persist for weeks to months.<br><strong>B symptoms<\/strong>&nbsp;(fever, night sweats, weight loss) are less common than in other subtypes.&nbsp;<\/li>\n\n\n\n<li><strong>Morphological<\/strong><br>The histologic image shows a&nbsp;<strong>lymphocyte-rich infiltrate<\/strong>&nbsp;(predominantly T lymphocytes) in the marginal and mantle zones of the lymph follicles<br>It is characterized by a&nbsp;<strong>diffuse fibrosis<\/strong>&nbsp;and a small number of H-RS cells<br>The environment consists of a mixture of lymphocytes, histiocytes and granulocytes<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_-methodik-10\"><\/span>Differential diagnosis and methodology<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Differential diagnosis is crucial, as the LR type can be confused morphologically and immunophenotypically with other lymphomas:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Aggressive T-cell histiocyte-rich large B-cell lymphoma (TCHRBCL)<\/strong><br>This aggressive non-Hodgkin's lymphoma may have similar morphologic features, in particular a rich lymphocytic environment<br>In terms of differential diagnosis, it is crucial that TCHRBCL&nbsp;<strong>CD20-positive<\/strong>&nbsp;is, but&nbsp;<strong>CD30-negative<\/strong>&nbsp;and&nbsp;<strong>CD15-negative<\/strong><br>The tumor cells are&nbsp;<strong>MUM1-positive<\/strong>&nbsp;and show a high proliferation rate<\/li>\n\n\n\n<li><strong>Reactive proliferation of germinal centers (PTKZ)<\/strong><br>These can be irritated by a lymphocyte-rich environment and occasional H-RS-like cells<br>The criteria for differentiation are&nbsp;<strong>Absence of CD30- and CD15-positive H-RS cells<\/strong>&nbsp;and the&nbsp;<strong>positive B-cell marker<\/strong>&nbsp;(CD20, CD79a, CD45) in the reactive cells<br>The&nbsp;<strong>EBV negativity<\/strong>&nbsp;is also typical<\/li>\n\n\n\n<li><strong>Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)<\/strong><br>Although NLPHL also shows a lymphocyte-rich environment, the tumor cells are&nbsp;<strong>CD20-positive<\/strong>,&nbsp;<strong>CD30-negative<\/strong>&nbsp;and&nbsp;<strong>CD15-negative<\/strong><br>The cells are&nbsp;<strong>EBV-negative<\/strong>&nbsp;and show a characteristic&nbsp;<strong>Lymphocyte predominance<\/strong>&nbsp;with small lymphocytes and epithelioid cells<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The differential diagnosis requires a&nbsp;<strong>Careful histological and immunophenotypic analysis<\/strong>, to differentiate with aggressive lymphomas such as TCHRBCL or reactive proliferations.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-33\"><\/span>Therapy<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">As the LR type is a&nbsp;<strong>Very good forecast<\/strong>&nbsp;a&nbsp;<strong>Risk-adapted therapy<\/strong>&nbsp;applied.<br>Patients with early stages (I-II) often receive&nbsp;<strong>short chemotherapies<\/strong>&nbsp;(e.g. ABVD) in combination with&nbsp;<strong>certain irradiation<\/strong><br>For advanced stages (III-IV), a&nbsp;<strong>more intensive chemotherapy<\/strong>&nbsp;(e.g. BEACOPP), but with lower irradiation requirements<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-32\"><\/span>Forecast<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>5-year survival rate is over 90 %<\/strong>.<br>The favorable forecast is due to the&nbsp;<strong>High sensitivity to chemotherapy and radiation<\/strong>&nbsp;attributable.<br>However, late complications (e.g. secondary tumors, cardiovascular diseases) are possible in younger patients and require careful follow-up care.&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>Classical lymphocyte-poor Hodgkin's lymphoma (cHL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The <strong>Classical lymphocyte-poor Hodgkin's lymphoma (cHL)<\/strong>&nbsp;is a rare form of Hodgkin's lymphoma that affects about&nbsp;<strong>1 % of cases<\/strong>&nbsp;and especially with&nbsp;<strong>older patients<\/strong>&nbsp;performance.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It is characterized by a&nbsp;<strong>Diffuse, blastic infiltrate<\/strong>&nbsp;with&nbsp;<strong>few lymphocytes<\/strong>&nbsp;and&nbsp;<strong>atypical Hodgkin and Reed-Sternberg cells (H-RS cells)<\/strong>&nbsp;which are often accompanied by mitoses and necrosis.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Histologically there is a&nbsp;<strong>diffuse HRS cell infiltration<\/strong>&nbsp;with only a sparse accompanying non-neoplastic reaction, resulting in a&nbsp;<strong>sarcomatous image<\/strong>&nbsp;can lead to.&nbsp;<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Klinisches_Bild_und_morphologische_Merkmale-6\"><\/span>Clinical picture and morphological features<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Primary localization<\/strong><br>Frequently&nbsp;<strong>abdominal lymph node involvement<\/strong>, especially in the area of the mesentery or retroperitoneally<\/li>\n\n\n\n<li><strong>Symptoms<\/strong><br>Typically&nbsp;<strong>B symptoms<\/strong>&nbsp;(fever, night sweats, unintentional weight loss &gt;10 % in 6 months), which occur more frequently in this subtype<\/li>\n\n\n\n<li><strong>Sleeve<\/strong><br>Prefers patients in the&nbsp;<strong>older age<\/strong>&nbsp;(mostly &gt;60 years), with a&nbsp;<strong>Male preference<\/strong><\/li>\n\n\n\n<li><strong>Morphology<\/strong><br>H-RS cells are&nbsp;<strong>pleomorphic<\/strong>, with large, granular nuclei and prominent nucleoli; lymphocytes are minimally present<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnostik_und_-methodik-11\"><\/span>Differential diagnosis and methodology<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>lymphocyte-poor classical Hodgkin's lymphoma (cHL)<\/strong>&nbsp;must be distinguished from the following diseases in particular:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Anaplastic large cell lymphoma (ALK-negative)<\/strong><br>This differential diagnosis is particularly important as both diseases have similar morphological and immunophenotypic characteristics (e.g. CD30+, CD15+)<br><strong>Immunohistochemistry<\/strong>&nbsp;(CD20-, CD30+, CD15+, ALK-) and&nbsp;<strong>molecular biology analyses<\/strong>&nbsp;(e.g.&nbsp;&nbsp;<em>ALK<\/em>-genre arrangements) are crucial for differentiating<\/li>\n\n\n\n<li><strong>Reactive lymph node changes<\/strong>&nbsp;(e.g. in the case of infections or autoimmune diseases)<br>Due to missing clonal cell population and missing H-RS cells<\/li>\n\n\n\n<li><strong>Aggressive B-cell lymphoma (e.g. T-cell histiocyte-rich large B-cell lymphoma, TCHRBCL)<\/strong><br>Differentiation through&nbsp;<strong>CD20 positivity<\/strong>&nbsp;(at TCHRBCL),&nbsp;<strong>CD30 positivity<\/strong>&nbsp;and&nbsp;<strong>CD15 negativity<\/strong>&nbsp;at TCHRBCL<br>In contrast to cHL, the H-RS cell structure is not typical for TCHRBCL<\/li>\n\n\n\n<li><strong>EBV-associated diseases<\/strong>, especially&nbsp;<strong>EBV-positive mucocutaneous ulcer<\/strong>, as CD30+ and CD15+ cells can also occur here<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostik-7\"><\/span>Diagnostics<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Histological diagnosis<\/strong><br>Only through&nbsp;<strong>Lymph node biopsy<\/strong>&nbsp;with&nbsp;<strong>whole lymph node<\/strong>&nbsp;possible<br><strong>Fine needle aspiration (cytology)<\/strong>&nbsp;is insufficient!<\/li>\n\n\n\n<li><strong>Immunohistochemistry<\/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>EBV positivity<\/strong>&nbsp;can be variable<\/li>\n\n\n\n<li><strong>Imaging<\/strong><br><strong>PET-CT<\/strong>&nbsp;for staging and treatment planning<br><strong>CT thorax\/abdomen<\/strong>&nbsp;with contrast medium<\/li>\n\n\n\n<li><strong>Staging<\/strong><br>After&nbsp;<strong>modified Ann Arbor classification<\/strong>&nbsp;(Stage I-IV)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-34\"><\/span>Therapy<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Therapy principle<\/strong><br><strong>Polychemotherapy<\/strong>&nbsp;(e.g.&nbsp;&nbsp;<strong>BEACOPP<\/strong>-protocol) with or without&nbsp;<strong>Irradiation<\/strong>.&nbsp;<\/li>\n\n\n\n<li><strong>Risk-adapted therapy<\/strong><br>Due to the poor prognosis, this subtype is often treated with a&nbsp;<strong>intensive chemotherapy<\/strong>&nbsp;recommended<\/li>\n\n\n\n<li><strong>New therapies<\/strong><br>In case of recurrence or treatment failure:&nbsp;<strong>Antibody therapies<\/strong>&nbsp;(e.g.&nbsp;&nbsp;<strong>Brentuximab vedotin<\/strong>, an anti-CD30 antibody),&nbsp;<strong>Checkpoint inhibitors<\/strong>&nbsp;(e.g.&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>Forecast<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Worst forecast<\/strong>&nbsp;of all Hodgkin's lymphoma subtypes<\/li>\n\n\n\n<li><strong>5-year survival rate<\/strong><br>Significantly lower compared to other subtypes (below 75 %, depending on staging and therapy)<\/li>\n\n\n\n<li><strong>Risk of recurrence<\/strong><br>is high, therefore&nbsp;<strong>Intensive aftercare<\/strong>&nbsp;with regular PET-CT and clinical checks required<\/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>Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The <strong>Nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL)<\/strong>&nbsp;is a rare subtype of Hodgkin's lymphoma, accounting for about&nbsp;<strong>5\u201310 % of all Hodgkin lymphoma cases<\/strong>&nbsp;makes the difference.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It is characterized by a&nbsp;<strong>cheap forecast<\/strong>, a&nbsp;<strong>Tendency towards limited lymph node involvement<\/strong>&nbsp;(especially the neck, axilla and groin region) and a&nbsp;<strong>Low frequency of B-symptoms<\/strong>&nbsp;(fever, night sweats, weight loss).&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>Clinical picture and morphological features<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Sleeve<\/strong><br>Typically begins before the age of 40, with a male proportion of about&nbsp;<strong>3:1<\/strong><\/li>\n\n\n\n<li><strong>Clinical picture<\/strong><br>Most&nbsp;<strong>limited stage I or II disease (&gt;80 % of cases)<\/strong>.<br>Mediastinal involvement is rare<br>Extranodal manifestations only occur in&nbsp;<strong>10-15 % of cases in the spleen<\/strong>, less frequently in the liver, bone marrow or lungs<\/li>\n\n\n\n<li><strong>Morphology<\/strong><br>Histologically characterized by&nbsp;<strong>lymphocyte-predominant (LP) cells<\/strong>which&nbsp;<strong>CD20-positive<\/strong>,&nbsp;<strong>CD15-negative<\/strong>&nbsp;and&nbsp;<strong>CD30-negative<\/strong>&nbsp;are.<br>These cells are monoclonal B cells originating from the germinal center.<br>In contrast to classic Hodgkin's lymphoma, typical Hodgkin's and Reed-Sternberg cells are absent.<br>The tumor cells are located in&nbsp;<strong>nodular structures<\/strong>, often surrounded by a dense lymphocyte envelope, before<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Differenzialdiagnosen_und_Differenzialmethodik\"><\/span><strong>Differential diagnoses and differential methodology<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The differential diagnosis is crucial, as NLPHL overlaps morphologically and immunophenotypically with other lymphomas.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The most important differential diagnoses are<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Classical lymphocyte-rich Hodgkin's lymphoma (cHL, lymphocyte-rich type)<\/strong><br>- <strong>Difference<\/strong>Although both have a lymphocyte-rich environment, the tumor cells in cHL&nbsp;<strong>CD20-negative<\/strong>,&nbsp;<strong>CD15-positive<\/strong>&nbsp;and&nbsp;<strong>CD30-positive<\/strong>, in contrast to NLPHL<br>- <strong>Differentiation<\/strong>: Immunophenotype is decisive<\/li>\n\n\n\n<li><strong>Progressive Transformation of Germinal Centers (PTGC)<\/strong><br>- <strong>Difference<\/strong>PTC is a&nbsp;<strong>premalignant, non-clonal<\/strong>&nbsp;Change that appears very similar histologically<br>- <strong>Differentiation<\/strong>Clonality (e.g. through&nbsp;<strong>PCR for immunoglobulin genes<\/strong>) shows monoclonal B-cell proliferation in NLPHL, but polyclonal B-cell proliferation in PTC.<\/li>\n\n\n\n<li><strong>T-cell\/histiocyte-rich large B-cell lymphoma (THRLBCL)<\/strong><br>- <strong>Difference<\/strong>THRLBCL shows&nbsp;<strong>Aggressive clinical behavior<\/strong>, advanced stage and poor prognosis<br>- <strong>Differentiation<\/strong>Histologically similar patterns (diffuse, atypical), but&nbsp;<strong>T cells dominate<\/strong>,&nbsp;<strong>CD20-positive with B cells<\/strong>,&nbsp;<strong>no LP cells<\/strong><br>- <strong>Molecular<\/strong>THRLBCL shows&nbsp;<strong>Clonal T-cell receptor rearrangement<\/strong>&nbsp;- in contrast to NLPHL, which&nbsp;<strong>B-cell clonal rearrangement<\/strong>&nbsp;has<\/li>\n\n\n\n<li><strong>Follicular lymphoma (FL)<\/strong><br>- <strong>Difference<\/strong>FL is a&nbsp;<strong>Non-Hodgkin lymphoma<\/strong>, with&nbsp;<strong>follicular proliferation<\/strong>&nbsp;and&nbsp;<strong>B cells<\/strong>which&nbsp;<strong>CD20-positive<\/strong>,&nbsp;<strong>CD10-positive<\/strong>&nbsp;are<br>- <strong>Differentiation<\/strong>No LP cells, no T cell-histiocyte overlap.&nbsp;<strong>CD21-positive<\/strong>&nbsp;in follicles (in contrast to NLPHL)<\/li>\n\n\n\n<li><strong>Angioimmunoblastic T-cell lymphoma (AITL)<\/strong><br>- <strong>Difference<\/strong>: Shows&nbsp;<strong>T-cell clonal rearrangement<\/strong>,&nbsp;<strong>CD4-positive<\/strong>,&nbsp;<strong>CD10-negative<\/strong>,&nbsp;<strong>CD21-negative<\/strong><br>- <strong>Differentiation<\/strong>:&nbsp;<strong>Vessel density and T-cell infiltrate<\/strong>&nbsp;(high for AITL, low for NLPHL) and&nbsp;<strong>CD20-positive with T cells<\/strong>&nbsp;in the AITL<\/li>\n\n\n\n<li><strong>Follicular T-cell lymphoma (FTCL)<\/strong><br>- <strong>Difference<\/strong>:&nbsp;<strong>T-cell clonal rearrangement<\/strong>,&nbsp;<strong>CD4-positive<\/strong>,&nbsp;<strong>CD8-negative<\/strong>,&nbsp;<strong>CD20-negative<\/strong><br>- <strong>Differentiation<\/strong>: Molecular detection of a&nbsp;<strong>T-cell receptor rearrangement<\/strong><\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Diagnostik-8\"><\/span><strong>Diagnostics<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Lymph node biopsy<\/strong>&nbsp;with histological and immunophenotypic analysis<\/li>\n\n\n\n<li><strong>Central marker<\/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>Molecular biology<\/strong><br><strong>PCR for immunoglobulin genes<\/strong>&nbsp;to ensure B-cell clonality<\/li>\n\n\n\n<li><strong>Staging<\/strong><br><strong>Cotswold staging system<\/strong>&nbsp;to determine the degree of severity and spread<\/li>\n\n\n\n<li><strong>Biopsy for recurrence<\/strong><br><strong>Mandatory<\/strong>, yes&nbsp;<strong>Transformation into diffuse large B-cell lymphoma (DLBCL)<\/strong>&nbsp;approximately&nbsp;<strong>10 % of cases within 10 years<\/strong>&nbsp;appearance<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Therapie-35\"><\/span><strong>Therapy<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Stage IA without risk factors<\/strong><br>- <strong>Irradiation of the affected area (IFRT)<\/strong>&nbsp;with 30\u201336 Gy&nbsp;<\/li>\n\n\n\n<li><strong>Stage IA with risk factors or higher stage (II-IV)<\/strong><br>- <strong>Similar to classic HL<\/strong>:&nbsp;<strong>Chemotherapy (e.g. ABVD)<\/strong>&nbsp;or&nbsp;<strong>Combined therapy<\/strong><br>- <strong>Protocols from B-cell non-Hodgkin's lymphoma therapy (B-NHL)<\/strong>&nbsp;are also effective<\/li>\n\n\n\n<li><strong>Recurrence<\/strong><br>- <strong>Rituximab (anti-CD20 antibody)<\/strong>&nbsp;is&nbsp;<strong>Very effective<\/strong><br>- High-dose chemotherapy with&nbsp;<strong>autologous stem cell transplantation<\/strong>&nbsp;only for&nbsp;<strong>few cases<\/strong>&nbsp;required<\/li>\n\n\n\n<li><strong>New approaches<\/strong><br>Check clinical studies&nbsp;<strong>Rituximab + chemotherapy<\/strong>&nbsp;in the first line, especially in higher stages<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Prognose-34\"><\/span><strong>Forecast<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Very good<\/strong><br>- <strong>10-year survival rate &gt;90 %<\/strong>&nbsp;for limited illness<br>- <strong>First-line therapy leads to remission in 90-100 %<\/strong><\/li>\n\n\n\n<li><strong>Recurrence rate<\/strong><br><strong>10-15 %<\/strong>, mostly&nbsp;<strong>3\u20136 years after diagnosis<\/strong><\/li>\n\n\n\n<li><strong>Long-term consequences<\/strong><br>- <strong>Secondary malignancies<\/strong><br>\u2013 \u2013 <strong>Diffuse large B-cell lymphoma (DLBCL)<\/strong>:&nbsp;<strong>25 % Risk after 20 years<\/strong><br>\u2013 \u2013 <strong>Carcinomas (lung, breast, gastrointestinal tract)<\/strong> often in irradiated regions<br>\u2013 \u2013 <strong>Cardiopulmonary diseases<\/strong>&nbsp;as a result of radiotherapy<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The&nbsp;<strong>Differential diagnosis is critical<\/strong>, especially with&nbsp;<strong>THRLBCL, PTC, FL and AITL<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The therapy is&nbsp;<strong>stage-adapted<\/strong>, with&nbsp;<strong>Radiation for early stages<\/strong>&nbsp;and&nbsp;<strong>Chemotherapy for advanced cases<\/strong>.&nbsp;<strong>Rituximab<\/strong>&nbsp;is the therapy of choice.<\/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>Standard therapeutics (chemo)<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Chemotherapy for lymphomas depends on the type (Hodgkin's vs. non-Hodgkin's lymphoma), the stage and the risk profile.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Common undesirable side effects are (see below for specific side effects):<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Myelosuppression (anemia, neutropenia, thrombocytopenia)<\/li>\n\n\n\n<li>Nausea, vomiting, tiredness (fatigue)<\/li>\n\n\n\n<li>Hair loss<\/li>\n\n\n\n<li>Immunosuppression<\/li>\n\n\n\n<li>Fertility impairment (in men and women)<\/li>\n\n\n\n<li>Secondary tumors (long-term, especially with alkylants and topoisomerase II inhibitors such as etoposide)<\/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>Hodgkin's lymphoma<\/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\">Standard in early and advanced stages:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Bleomycin<\/strong><br>Pulmonary fibrosis (dose-dependent), pneumonitis (rare but serious)<\/li>\n\n\n\n<li><strong>Doxorubicin<\/strong><br>Cardiotoxicity (dose-dependent), hair loss, nausea<\/li>\n\n\n\n<li><strong>Vinblastine<\/strong><br>Neuropathy (sensory disturbances), constipation<\/li>\n\n\n\n<li><strong>Dacarbazine<\/strong><br>Nausea, fatigue, myelo-suppressive.<br>\u2192 Lower hematotoxicity than BEACOPP, but lung and heart risk<\/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\">For medium to high risk:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Bleomycin<\/strong><br>Pulmonary fibrosis (dose-dependent), pneumonitis (rare but serious)<\/li>\n\n\n\n<li>Adriamycin<\/li>\n\n\n\n<li><strong>vincristine<\/strong> (Oncovin)<br>Neuropathy (tingling, furred skin), constipation<br>\u2192&nbsp;<strong>Higher acute toxicity<\/strong>, especially hematological; increased risk of secondary tumors in the long term<\/li>\n\n\n\n<li><strong>Prednisolone<\/strong><br><strong>Frequently<\/strong>Weight gain, increased appetite, water retention (edema), redistribution of fatty tissue (truncal obesity, moon face, bull neck), increased blood sugar (risk of diabetes), immunosuppression (increased susceptibility to infections), osteoporosis, muscle loss, sleep disorders.<br><strong>Occasionally<\/strong>Skin changes (thin skin, stretch marks, acne), eye problems (cataracts, glaucoma), high blood pressure, gastrointestinal complaints (ulcers).&nbsp;<br><strong>Rarer<\/strong>Mood swings, depression, euphoria, psychotic states, headaches, menstrual disorders, impotence.&nbsp;<br><strong>Long-term use<\/strong>Risk of kidney damage, premature arteriosclerosis, adrenal dysfunction.<\/li>\n\n\n\n<li><strong>Etoposide<\/strong><br>Myelosuppression (neutropenia, thrombocytopenia), increased risk of infection<\/li>\n\n\n\n<li><strong>Cyclophosphamide<\/strong><br>Bladder damage (hemorrhagic cystitis), myelosuppressive<\/li>\n\n\n\n<li><strong>Procarbazine<\/strong><br>Myelosuppression, gastrointestinal toxicity, interaction with MAO inhibitors<\/li>\n\n\n\n<li><strong>vincristine<\/strong><br>Neuropathy (tingling, furred skin), constipation<br>\u2192&nbsp;<strong>Higher acute toxicity<\/strong>, especially hematological; increased risk of secondary tumors in the long term<\/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\">New standard in advanced stages (18-60 years)<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Brentuximab vedotin<\/strong><br><strong>Peripheral neuropathy<\/strong>&nbsp;(sensory\/motor), most common specific side effect, in up to 50 % of patients, leads to discontinuation of therapy in 23 %<br><strong>Demyelinating polyneuropathy<\/strong>, rare but serious (e.g. Guillain-Barr\u00e9-like).&nbsp;<br><strong>Infusion reactions and anaphylactic reactions<\/strong> due to the antibody component.&nbsp;<br>!- <strong>Pulmonary toxicity<\/strong>, absolute contraindication with&nbsp;<strong>Bleomycin<\/strong>&nbsp;\u2013 <strong>Life-threatening pulmonary fibrosis possible<\/strong> - !<br><strong>Rare but severe skin reactions<\/strong> - <strong>Stevens-Johnson syndrome<\/strong>&nbsp;and toxic epidermal necrolysis<br><strong>Progressive multifocal leukoencephalopathy (PML)<\/strong> due to JC virus reactivation, <strong>potentially fatal<\/strong><br><strong>Tumor lysis syndrome<\/strong> for high tumor burden<br><strong>Fertility restriction<\/strong>, Possible impairment of male fertility - freezing of sperm recommended before starting therapy<\/li>\n\n\n\n<li><strong>Etoposide<\/strong><br>Myelosuppression (neutropenia, thrombocytopenia), increased risk of infection<\/li>\n\n\n\n<li><strong>Cyclophosphamide<\/strong><br>Bladder damage (hemorrhagic cystitis), myelosuppressive<\/li>\n\n\n\n<li><strong>Doxorubicin<\/strong><br>Cardiotoxicity (dose-dependent), hair loss, nausea<\/li>\n\n\n\n<li><strong>Dacarbazine<\/strong><br>Nausea, fatigue, myelo-suppressive.<br>\u2192 Lower hematotoxicity than BEACOPP, but lung and heart risk<\/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>Non-Hodgkin's lymphoma (NHL)<\/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\">Basic regime, often combined with <strong>Rituximab<\/strong> (<strong>R-CHOP<\/strong>)<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cyclophosphamide<\/strong><br>Bladder damage (hemorrhagic cystitis), myelosuppressive<\/li>\n\n\n\n<li><strong>vincristine<\/strong> (Oncovin)<br>Neuropathy (tingling, furred skin), constipation<br>\u2192&nbsp;<strong>Higher acute toxicity<\/strong>, especially hematological; increased risk of secondary tumors in the long term<\/li>\n\n\n\n<li><strong>Doxorubicin<\/strong><br>Cardiotoxicity (dose-dependent), hair loss, nausea<\/li>\n\n\n\n<li><strong>Prednisone<\/strong> - Prednisone is a&nbsp;<strong>Prodrug<\/strong>&nbsp;and must be activated via the liver \u2192 prednisolone is preferable in the case of liver dysfunction.<br><strong>Frequently<\/strong>Weight gain, increased appetite, water retention (edema), redistribution of fatty tissue (truncal obesity, moon face, bull neck), increased blood sugar (risk of diabetes), immunosuppression (increased susceptibility to infections), osteoporosis, muscle loss, sleep disorders.<br><strong>Occasionally<\/strong>Skin changes (thin skin, stretch marks, acne), eye problems (cataracts, glaucoma), high blood pressure, gastrointestinal complaints (ulcers).&nbsp;<br><strong>Rarer<\/strong>Mood swings, depression, euphoria, psychotic states, headaches, menstrual disorders, impotence.&nbsp;<br><strong>Long-term use<\/strong>Risk of kidney damage, premature arteriosclerosis, adrenal dysfunction.<br><\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"R-Bendamustin\"><\/span><strong>R-Bendamustine<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Alternative to R-CHOP, especially for older patients<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Rituximab<\/strong><br>Infusion reactions.<br>\u2192 Severe kidney and nerve damage possible<\/li>\n\n\n\n<li><strong>Bendamustine<\/strong><br>Myelosuppression, susceptibility to infections, skin reactions<br>Lower risk of hair loss and neuropathy<\/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\">Intensive therapies for relapse, before stem cell transplantation<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Rituximab<\/strong><br>Infusion reactions.<br>\u2192 Severe kidney and nerve damage possible<\/li>\n\n\n\n<li><strong>Dexamethasone<\/strong><br><strong>Higher risk of osteoporosis<\/strong>&nbsp;compared to other glucocorticoids, especially due to calcium loss.&nbsp;<br><strong>Pheochromocytoma crisis<\/strong> Rare, but life-threatening, with symptoms such as high blood pressure, headaches, sweating and palpitations in unknown adrenal gland tumors<br><strong>Severe anaphylactic reactions<\/strong>Rare, but possible, up to circulatory failure, cardiac arrest or bronchospasm<br><strong>Central side effects<\/strong> Mental disorders (euphoria, intoxication, depression), insomnia, headaches, rarely epileptic seizures or pseudotumor cerebri (increase in intracranial pressure)<br><strong>Intravenous administration too fast<\/strong> can lead to short-term paraesthesia (tingling, burning), flushing or vein irritation, therefore run in slowly (2-3 minutes)<br><strong>Contraindication for certain infections<\/strong> due to the risk of activation of latent infections (e.g. chickenpox, measles, dwarf threadworm)<br><strong>Eyes<\/strong> Risk of glaucoma and cataract, especially with ocular or prolonged use.&nbsp;<br><strong>Joint injection<\/strong> Rarely tendon rupture or vertebral body fracture<\/li>\n\n\n\n<li><strong>High-dose cytarabine<\/strong> (Cytarabine)<br>Ataxia, conjunctivitis, myelosuppressive<\/li>\n\n\n\n<li><strong>Platinum<\/strong> (Cisplatin)<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\">Intensive therapies for relapse, before stem cell transplantation<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Rituximab<\/strong><br>Infusion reactions.<br>\u2192 Severe kidney and nerve damage possible<\/li>\n\n\n\n<li><strong>Ifosfamide<\/strong><br>Neurotoxicity (encephalopathy), urinary bladder damage (mesna protection required)<\/li>\n\n\n\n<li><strong>Carboplatin<\/strong><br>Myelosuppression (sharp drop in blood values)<\/li>\n\n\n\n<li><strong>Etoposide<\/strong><br>Myelosuppression, secondary leukemia risk.<br>\u2192 Less nephro- and ototoxicity than cisplatin, but higher neuro- and bladder toxicity<\/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\">For indolent forms such as follicular lymphoma<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cyclophosphamide<\/strong><br>Bladder damage (hemorrhagic cystitis), myelosuppressive<\/li>\n\n\n\n<li><strong>vincristine<\/strong> (Oncovin)<br>Neuropathy (tingling, furred skin), constipation<br>\u2192&nbsp;<strong>Higher acute toxicity<\/strong>, especially hematological; increased risk of secondary tumors in the long term<\/li>\n\n\n\n<li><strong>Prednisone<\/strong> - Prednisone is a&nbsp;<strong>Prodrug<\/strong>&nbsp;and must be activated via the liver \u2192 prednisolone is preferable in the case of liver dysfunction.<br><strong>Frequently<\/strong>Weight gain, increased appetite, water retention (edema), redistribution of fatty tissue (truncal obesity, moon face, bull neck), increased blood sugar (risk of diabetes), immunosuppression (increased susceptibility to infections), osteoporosis, muscle loss, sleep disorders.<br><strong>Occasionally<\/strong>Skin changes (thin skin, stretch marks, acne), eye problems (cataracts, glaucoma), high blood pressure, gastrointestinal complaints (ulcers).&nbsp;<br><strong>Rarer<\/strong>Mood swings, depression, euphoria, psychotic states, headaches, menstrual disorders, impotence.&nbsp;<br><strong>Long-term use<\/strong>Risk of kidney damage, premature arteriosclerosis, adrenal dysfunction.<\/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>Special shapes<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Mantle cell lymphoma<\/strong><br>Often intensive with R-DHAP or R-CHOP, followed by high-dose chemotherapy + stem cell transplantation<\/li>\n\n\n\n<li><strong>T-cell lymphomas<\/strong><br>CHOP-based regimens, possibly with etoposide (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>Standard therapeutics - signaling pathways<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>Bendamustine<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Alkylation of the DNA<\/strong>Bendamustine is a&nbsp;<strong>bifunctional alkylane<\/strong>&nbsp;(nitrogen oxide derivative), which forms electrophilic alkyl groups. These bind covalently to the&nbsp;<strong>N7 position of guanine<\/strong>&nbsp;in the DNA \u2192 leads to&nbsp;<strong>intra- and interstrand DNA cross-links<\/strong><\/li>\n\n\n\n<li>The cross-links interfere&nbsp;<strong>DNA replication<\/strong>,&nbsp;<strong>Transcription<\/strong>&nbsp;and&nbsp;<strong>Repair<\/strong>&nbsp;\u2192 DNA strand breaks (especially double strand breaks)<\/li>\n\n\n\n<li>Activation of&nbsp;<strong>p53<\/strong>&nbsp;and&nbsp;<strong>DNA damage response<\/strong>&nbsp;\u2192 Cell cycle arrest and&nbsp;<strong>Apoptosis<\/strong><\/li>\n\n\n\n<li>Inhibits the&nbsp;<strong>Alkyltransferase repair pathway<\/strong>&nbsp;and instead favors the&nbsp;<strong>Nucleotide excision repair pathway<\/strong>, which makes the repair more difficult<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Additional effect<\/strong>: Purine analog structure \u2192&nbsp;<strong>inhibits purine synthesis<\/strong>&nbsp;(antimetabolite properties).&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Effective&nbsp;<strong>Cycle non-specific<\/strong>, also against dormant cells.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Shows activity in alkylansiene-resistant tumors, as the repair of DNA damage is slower and less efficient.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Bleomycin\"><\/span>Bleomycin<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Binds to&nbsp;<strong>Iron(II)<\/strong>&nbsp;(Fe\u00b2\u207a) and forms a&nbsp;<strong>Bleomycin-Fe(II) complex<\/strong><\/li>\n\n\n\n<li>This complex reacts with&nbsp;<strong>oxygen<\/strong>&nbsp;and forms&nbsp;<strong>reactive oxygen species (ROS)<\/strong>&nbsp;such as superoxide and hydroxyl radicals<\/li>\n\n\n\n<li>The ROS cause&nbsp;<strong>DNA strand breaks<\/strong>&nbsp;(single and double-strand breaks), especially on&nbsp;<strong>G-C-rich sequences<\/strong><\/li>\n\n\n\n<li>Specific damage caused by&nbsp;<strong>Abstraction of the 4\u2032-H atom<\/strong>&nbsp;at the deoxyribose \u2192 break in the DNA backbone<\/li>\n\n\n\n<li>Resulting&nbsp;<strong>free base propenals<\/strong>&nbsp;(e.g. of thymine) contribute to cytotoxicity<\/li>\n\n\n\n<li>DNA damage leads to&nbsp;<strong>Cell cycle arrest in the G\u2082 phase<\/strong>&nbsp;\u2192 Inhibition of mitosis \u2192&nbsp;<strong>Apoptosis<\/strong><\/li>\n\n\n\n<li>Bleomycin acts as&nbsp;<strong>Pseudoenzyme<\/strong>, which can catalyze DNA damage multiple times.&nbsp;<\/li>\n\n\n\n<li>Additional inhibition of the&nbsp;<strong>DNA-dependent DNA polymerase<\/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>Cisplatin \/ carboplatin<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Both act as&nbsp;<strong>Platinum-based alkylans<\/strong>, form after intracellular activation&nbsp;<strong>electrophilic aquo-complexes<\/strong>. These bind preferentially to&nbsp;<strong>N7 position of guanine and adenine<\/strong>&nbsp;in the DNA.<br>Emergence&nbsp;<strong>DNA cross-links<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Intrastrand cross-linking<\/strong>&nbsp;(within a strand)<\/li>\n\n\n\n<li><strong>Interstrand cross-linking<\/strong>&nbsp;(between both strands)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">DNA deformation blocked&nbsp;<strong>Replication and transcription<\/strong>.&nbsp;<br>Activation of&nbsp;<strong>DNA damage responses<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>p53 activation<\/strong>&nbsp;\u2192 Cell cycle arrest (usually in G2\/M phase)<\/li>\n\n\n\n<li>Induction of&nbsp;<strong>Apoptosis<\/strong>&nbsp;via mitochondrial and caspase-dependent pathways<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Additional effects:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Inhibition of the&nbsp;<strong>DNA repair<\/strong><\/li>\n\n\n\n<li>Inhibition of the&nbsp;<strong>Telomerase activity<\/strong><\/li>\n\n\n\n<li>Induction of&nbsp;<strong>Point mutations<\/strong><\/li>\n\n\n\n<li>At high concentrations:&nbsp;<strong>PARP hyperactivation<\/strong>&nbsp;\u2192 NAD+\/ATP degradation \u2192 Necrosis<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Carboplatin<\/strong>&nbsp;acts more slowly, but has the same mechanism of action as cisplatin \u2192&nbsp;<strong>Cross-resistance<\/strong>&nbsp;possible.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"9-cyclophosphamid\"><span class=\"ez-toc-section\" id=\"Cyclophosphamid\"><\/span><strong>Cyclophosphamide<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Cyclophosphamide is a&nbsp;<strong>Prodrug<\/strong>, which is produced in the liver by&nbsp;<strong>CYP2B6<\/strong>&nbsp;to&nbsp;<strong>4-hydroxycyclophosphamide<\/strong>&nbsp;is converted.&nbsp;<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>This decomposes into&nbsp;<strong>Aldophosphamide<\/strong>&nbsp;and on to&nbsp;<strong>Phosphoramide Mustard<\/strong>&nbsp;(active) and&nbsp;<strong>Acrolein<\/strong><\/li>\n\n\n\n<li><strong>Phosphoramide Mustard<\/strong>&nbsp;acts as&nbsp;<strong>bifunctional alkylane<\/strong>It transfers alkyl groups to the&nbsp;<strong>N7 position of guanine<\/strong>&nbsp;in the DNA<\/li>\n\n\n\n<li>This results in&nbsp;<strong>DNA-DNA cross-links (cross-links)<\/strong>&nbsp;and&nbsp;<strong>DNA-protein cross-links<\/strong>, which fix the DNA strands<\/li>\n\n\n\n<li>Blocking the cross-links&nbsp;<strong>DNA replication<\/strong>&nbsp;and&nbsp;<strong>Transcription<\/strong>, lead to&nbsp;<strong>Strand breaks<\/strong>&nbsp;and activate&nbsp;<strong>p53<\/strong>-dependent&nbsp;<strong>Apoptosis<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Effect is&nbsp;<strong>Cycle non-specific<\/strong>, but particularly effective in proliferating cells.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Acrolein<\/strong>&nbsp;causes the&nbsp;<strong>Bladder damage<\/strong>&nbsp;(hemorrhagic cystitis).<\/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>Cytarabine (Ara-C)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Cytarabine is converted intracellularly to&nbsp;<strong>Ara-CTP<\/strong>&nbsp;phosphorylated, the active metabolite<\/li>\n\n\n\n<li>Ara-CTP&nbsp;<strong>inhibits DNA polymerase<\/strong>&nbsp;and is incorrectly incorporated into the DNA \u2192&nbsp;<strong>Termination of the DNA chain<\/strong><\/li>\n\n\n\n<li>Blockade of the&nbsp;<strong>DNA replication and repair<\/strong>&nbsp;\u2192 Cell cycle arrest in the&nbsp;<strong>S phase<\/strong><\/li>\n\n\n\n<li>Induction of&nbsp;<strong>Apoptosis<\/strong>&nbsp;via DNA damage response (e.g. p53 activation)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Effect is&nbsp;<strong>Cycle phase specific<\/strong>&nbsp;(only in proliferating cells)<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Dacarbacin\"><\/span>Dacarbacin<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Dacarbazine is a&nbsp;<strong>Prodrug<\/strong>, which is produced in the liver by&nbsp;<strong>Cytochrome P450<\/strong>&nbsp;to&nbsp;<strong>Monomethyltriazenylimidazole carboxamide (MTIC)<\/strong>&nbsp;is metabolized.  MTIC spontaneously decomposes to a reactive&nbsp;<strong>Methyl cation<\/strong>, which is known as&nbsp;<strong>Alkylans<\/strong>&nbsp;works.&nbsp;<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Alkylation of the DNA<\/strong>: The methyl cation binds primarily to the&nbsp;<strong>O-6 and N-7 position of guanine<\/strong>&nbsp;in the DNA<\/li>\n\n\n\n<li>This leads to&nbsp;<strong>DNA strand breaks<\/strong>,&nbsp;<strong>Mismatches<\/strong>&nbsp;during replication and&nbsp;<strong>Blockade of DNA synthesis<\/strong><\/li>\n\n\n\n<li>Activate the damage&nbsp;<strong>DNA repair systems<\/strong>, but overloading or inefficient repair (e.g. low MGMT activity) results in&nbsp;<strong>Apoptosis<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Effect is&nbsp;<strong>Cycle-independent<\/strong>, but particularly effective in proliferating cells<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"9-dexamethason\"><span class=\"ez-toc-section\" id=\"Dexamethason\"><\/span><strong>Dexamethasone<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Binds to intracellular&nbsp;<strong>Glucocorticoid receptors<\/strong>&nbsp;\u2192 Complex migrates into the cell nucleus.&nbsp;<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Transrepression<\/strong>Inhibits the transcription factors&nbsp;<strong>NF-\u03baB<\/strong>&nbsp;and&nbsp;<strong>AP-1<\/strong>&nbsp;\u2192 reduces expression of pro-inflammatory genes (cytokines such as IL-1, IL-6, TNF-\u03b1; enzymes such as phospholipase A2, COX-2)<\/li>\n\n\n\n<li><strong>Transactivation<\/strong>Activates anti-inflammatory genes (e.g. for I\u03baB, which inhibits NF-\u03baB)<\/li>\n\n\n\n<li><strong>In lymphatic cells<\/strong><br>activates the&nbsp;<strong>intrinsic apoptosis pathway<\/strong>&nbsp;\u2192 Mitochondrial permeabilization, cytochrome c release, caspase-9 activation<\/li>\n\n\n\n<li><strong>In fibroblasts<\/strong><br>shows&nbsp;<strong>anti-apoptotic effect<\/strong>&nbsp;about:<br>- Induction of the&nbsp;<strong>Sphingosine kinase 1<\/strong>&nbsp;\u2192 increased production of&nbsp;<strong>Sphingosine-1-phosphate (S1P)<\/strong><br>- Activation of the&nbsp;<strong>PI3K\/Akt signal path<\/strong><br>- Up-regulation of the anti-apoptotic protein&nbsp;<strong>Bcl-xL<\/strong><br>- Preservation of the mitochondrial membrane potential<\/li>\n\n\n\n<li>Inhibits&nbsp;<strong>Phospholipase A2<\/strong>&nbsp;\u2192 Reduced release of pro-inflammatory mediators<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"9-doxorubicin\"><span class=\"ez-toc-section\" id=\"Doxorubicin\"><\/span><strong>Doxorubicin<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>DNA intercalation<\/strong>The planar molecule intercalates between DNA base pairs in a sequence-specific manner \u2192 interferes with helicases, blocks&nbsp;<strong>DNA replication<\/strong>&nbsp;and&nbsp;<strong>Transcription<\/strong><\/li>\n\n\n\n<li><strong>Topoisomerase II inhibition<\/strong>: Doxorubicin stabilizes the&nbsp;<strong>Topoisomerase II DNA cleavage complex<\/strong>&nbsp;\u2192 prevents DNA strands from reuniting \u2192 leads to&nbsp;<strong>Double-strand breaks<\/strong><\/li>\n\n\n\n<li><strong>ROS formation<\/strong>The quinone structure is reduced to a semiquinone radical \u2192 generated&nbsp;<strong>reactive oxygen species (ROS)<\/strong>&nbsp;\u2192 Oxidative damage to DNA, lipids and proteins \u2192 DNA strand breaks<\/li>\n\n\n\n<li><strong>Chromatin dynamics<\/strong>: Increases the&nbsp;<strong>Torsional stress<\/strong>&nbsp;in the DNA and promotes&nbsp;<strong>Nucleosome switching<\/strong>&nbsp;\u2192 Exposes DNA to further damage<\/li>\n\n\n\n<li><strong>Cell cycle arrest and apoptosis<\/strong>Activate DNA damage&nbsp;<strong>p53<\/strong>&nbsp;and&nbsp;<strong>DNA repair systems<\/strong>&nbsp;\u2192 in case of overload: cell cycle arrest (G2\/M) and&nbsp;<strong>Apoptosis<\/strong><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Effect is&nbsp;<strong>Cycle non-specific<\/strong>, but particularly effective in proliferating cells.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" id=\"9-etoposid\"><span class=\"ez-toc-section\" id=\"Etoposid\"><\/span><strong>Etoposide<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Inhibits&nbsp;<strong>Topoisomerase II<\/strong>, an enzyme that uncoils DNA during replication and transcription<\/li>\n\n\n\n<li>Binds to the&nbsp;<strong>Topoisomerase II DNA complex<\/strong>&nbsp;and stabilizes it \u2192 prevents the&nbsp;<strong>Re-ligation (reconnection)<\/strong>&nbsp;of the DNA strands after cleavage<\/li>\n\n\n\n<li>Leads to&nbsp;<strong>persistent double-strand breaks<\/strong>&nbsp;in the DNA<\/li>\n\n\n\n<li>Activate DNA damage&nbsp;<strong>p53<\/strong>&nbsp;and other repair mechanisms \u2192 in the event of overload:&nbsp;<strong>Cell cycle arrest in the G2 phase<\/strong><\/li>\n\n\n\n<li>Induction of the&nbsp;<strong>Apoptosis<\/strong>&nbsp;via mitochondrial and caspase-dependent signaling pathways<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Effect is&nbsp;<strong>Cycle phase specific<\/strong>, especially in the&nbsp;<strong>late S and G2 phase<\/strong>.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Glukokortikoide_Prednison_Prednisolon\"><\/span><strong>Glucocorticoids (prednisone \/ prednisolone)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Genomic effect<\/strong><br>Prednisone is converted in the liver to&nbsp;<strong>Prednisolone<\/strong>&nbsp;(active). Both bind to cytoplasmic&nbsp;<strong>Glucocorticoid receptors (GKR)<\/strong>.  The complex translocates into the cell nucleus and modulates gene expression via:<br>- <strong>Transactivation<\/strong>Binding to&nbsp;<strong>Glucocorticoid response elements (GRE)<\/strong>&nbsp;\u2192 increased expression of anti-inflammatory genes (e.g.&nbsp;&nbsp;<em>Lipocortin<\/em>, which inhibits phospholipase A2)<br>- <strong>Transrepression<\/strong>Inhibition of transcription factors&nbsp;<strong>NF-\u03baB<\/strong>&nbsp;and&nbsp;<strong>AP-1<\/strong>&nbsp;\u2192 reduced production of pro-inflammatory cytokines (IL-1, IL-2, IL-6, TNF-\u03b1, IFN-\u03b3), enzymes (COX-2, phospholipase A2) and leukotrienes<\/li>\n\n\n\n<li><strong>Non-genomic effect<\/strong><br>- At high doses (e.g. i.v.) rapid effect via membrane receptors \u2192 improved microcirculation in shock, increased effect of catecholamines<\/li>\n\n\n\n<li><strong>Further effects<\/strong><br>- Inhibition of fibroblast proliferation and collagen synthesis (antiproliferative)<br>- Immunosuppression through inhibition of proliferation of T lymphocytes<br>- Metabolic effects: Gluconeogenesis, lipolysis, proteolysis \u2192 increased blood sugar<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Ifosfamid\"><\/span><strong>Ifosfamide<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Prodrug<\/strong>Is produced in the liver by&nbsp;<strong>CYP450 enzymes<\/strong>&nbsp;(e.g. CYP3A4) to&nbsp;<strong>4-Hydroxy-Ifosfamide<\/strong>&nbsp;activated.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Spontaneous conversion to&nbsp;<strong>Isoaldophosphamide<\/strong>, which in&nbsp;<strong>Isophosphamide-Lost<\/strong>&nbsp;(alkylating) and&nbsp;<strong>Acrolein<\/strong>&nbsp;disintegrates<\/li>\n\n\n\n<li><strong>Isophosphamide-Lost<\/strong>&nbsp;transfers alkyl groups to the&nbsp;<strong>N7 position of guanine<\/strong>&nbsp;in the DNA \u2192 causes&nbsp;<strong>DNA strand breaks<\/strong>&nbsp;and&nbsp;<strong>Inter- and intrastrong cross-linking<\/strong><\/li>\n\n\n\n<li>This DNA damage blocks&nbsp;<strong>Replication<\/strong>&nbsp;and&nbsp;<strong>Transcription<\/strong>&nbsp;\u2192 lead to&nbsp;<strong>Cell cycle arrest in the G2 phase<\/strong><\/li>\n\n\n\n<li>If the repair mechanisms are overloaded (e.g. by MGMT) \u2192&nbsp;<strong>Apoptosis<\/strong><\/li>\n\n\n\n<li><strong>Acrolein<\/strong>&nbsp;causes the&nbsp;<strong>urotoxic effects<\/strong>&nbsp;(e.g. hemorrhagic cystitis)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Effect is&nbsp;<strong>Cycle non-specific<\/strong>, but particularly effective in proliferating cells.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Cross-resistance with cyclophosphamide possible<\/strong>but also <strong>Activity in cyclophosphamide-resistant tumors<\/strong>.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Procarbazin\"><\/span>Procarbazine<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Is oxidized in the liver (via CYP450) and spontaneously to&nbsp;<strong>Azo-procarbazine<\/strong>, then continue to&nbsp;<strong>Methylazoxy-<\/strong>&nbsp;and&nbsp;<strong>Benzylazoxy compounds<\/strong>.&nbsp;<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Alkylation of the DNA<\/strong>active metabolites (e.g.&nbsp;<strong>Methyl diazonium ion<\/strong>) alkylate the&nbsp;<strong>N7 position of guanine<\/strong>&nbsp;\u2192 leads to&nbsp;<strong>DNA single-strand breaks<\/strong>,&nbsp;<strong>Cross-linking<\/strong>&nbsp;and&nbsp;<strong>Mismatches<\/strong><\/li>\n\n\n\n<li><strong>Inhibition of protein synthesis<\/strong> inhibits the&nbsp;<strong>Transmethylation of methionine in t-RNA<\/strong>&nbsp;\u2192 Defective t-RNA \u2192 Termination of protein synthesis \u2192 Secondary inhibition of DNA and RNA synthesis<\/li>\n\n\n\n<li><strong>ROS formation<\/strong> - is formed during autooxidation&nbsp;<strong>Hydrogen peroxide<\/strong>&nbsp;\u2192 Oxidative damage to proteins (e.g. sulfhydryl groups)<\/li>\n\n\n\n<li><strong>Cell cycle arrest<\/strong> - Damage activates DNA repair mechanisms \u2192&nbsp;<strong>Cell cycle arrest<\/strong>&nbsp;\u2192 in case of overload&nbsp;<strong>Apoptosis<\/strong><\/li>\n\n\n\n<li><strong>Further effect<\/strong> is a weak&nbsp;<strong>MAO inhibition<\/strong>&nbsp;(central nervous system)<\/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\">The name results from<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>RI<\/strong>&nbsp;- Variable (defined by the manufacturer)<\/li>\n\n\n\n<li><strong>you<\/strong>&nbsp;- for \u201etumor\u201c<\/li>\n\n\n\n<li><strong>xi<\/strong>&nbsp;- for \u201echimeric\u201c (the variable region is murine, the constant region is human)<\/li>\n\n\n\n<li><strong>mab<\/strong>&nbsp;- for \u201emonoclonal antibody\u201c&nbsp;<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Rituximab binds to the&nbsp;<strong>CD20 antigen<\/strong>&nbsp;on B cells and activates several mechanisms of action:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Antibody-dependent cell-mediated cytotoxicity (ADCC)<\/strong>Fc region of the antibody activates natural killer cells that destroy the target cell<\/li>\n\n\n\n<li><strong>Complement-dependent cytotoxicity (CDC)<\/strong>Activation of the complement system (via C1q) \u2192 Formation of the membrane attack complex \u2192 Cell lysis<\/li>\n\n\n\n<li><strong>Direct apoptosis induction<\/strong>CD20-mediated signaling pathway \u2192 Activation of&nbsp;<strong>p38 MAP kinase<\/strong>&nbsp;\u2192 programmed cell death (apoptosis), especially after cross-linking of the antibody<\/li>\n\n\n\n<li><strong>Phagocytosis<\/strong>: Macrophages recognize and phagocytose labeled B cells<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">These mechanisms lead to <strong>selective elimination of CD20-positive B cells without affecting stem cells in the bone marrow<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Rituximab is a c<em>Himeric monoclonal antibody<\/em>, which comes from <em>murine<\/em> (mouse) variable domains and human (human) constant domains, interacts optimally with <em>Fc receptors<\/em> (crystallizable fragment \/ crystallizable fragment) on effector cells (<em>NK cells, monocytes, macrophages<\/em>) and the complement system.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Fc receptors<\/strong>&nbsp;are&nbsp;<strong>Membrane proteins on the surface of immune cells<\/strong>, that recognize and bind to the constant Fc portion of antibodies.&nbsp;<br>They combine humoral immunity (antibodies) with cell-mediated immunity by activating immune cells as soon as they bind to target cells (e.g., bacteria, tumor cells, viruses) marked with antibodies.<\/li>\n<\/ul>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>NK cells<\/strong> are a <strong>Lymphocyte type of the innate immune system<\/strong>, recognize and destroy infected and tumor cells without having to recognize specific antigens.<br>As soon as one cell has less <em>MHC-I molecules<\/em> (Surface proteins for the presentation of peptides from the cell interior, e.g., in viral infections or tumor formation) are presented as usual, it is recognized as foreign and killed.<\/li>\n<\/ul>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Monocytes<\/strong> arise, such as B cells (<em>B lymphocytes<\/em>), in the bone marrow and circulate in the blood as <strong>Part of the non-specific immune defense<\/strong>. Once they have migrated into tissue, they differentiate into macrophages.<\/li>\n<\/ul>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Macrophages<\/strong> are derived from monocytes as <strong>mature phagocytes<\/strong> All macrophages together manage around one million cells per second! They dispose of dead, destroyed cells and cell debris. A macrophage can phagocytose several hundred to a thousand cells a day.<\/li>\n<\/ul>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Complement system<\/strong> is <strong>Essential component of the innate immune system<\/strong>, consisting of 30 proteins that are produced in the liver and circulate in the plasma to supplement the effect of antibodies.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>This means:<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The rituximab structure:<br><br>\u251c\u2500 Variable domains (Fab part): MURINE (mouse sequence)<br>\u2502 \u2514\u2500 This part recognizes CD20<br>\u251c\u2500 Constant domains (Fc part): HUMAN (human sequence)<br>\u2502 \u2514\u2500 This part activates ADCC, CDC<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Finding out how and why it came about is a very exciting development that <a href=\"#hier\" data-type=\"internal\" data-id=\"#Rituximab\">here<\/a> is described in more detail below ...!<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Vincristin_Vinblastin\"><\/span><strong>Vincristine \/ vinblastine<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Binding to&nbsp;<strong>\u03b2-tubulin<\/strong>&nbsp;and inhibit the&nbsp;<strong>Polymerization of microtubules<\/strong>.&nbsp;<\/li>\n\n\n\n<li>Disturb the structure of the&nbsp;<strong>mitotic spindle<\/strong>&nbsp;during the metaphase \u2192&nbsp;<strong>Mitosearrest<\/strong>.&nbsp;<\/li>\n\n\n\n<li>Lead to&nbsp;<strong>Cell cycle arrest in the M phase<\/strong>&nbsp;and ultimately to&nbsp;<strong>Apoptosis<\/strong>.&nbsp;<\/li>\n\n\n\n<li>Effect&nbsp;<strong>Cycle phase specific<\/strong>&nbsp;against rapidly dividing cells (e.g. tumor cells).<\/li>\n\n\n\n<li>Vinblastine can also&nbsp;<strong>Crystallize tubulin<\/strong>&nbsp;leave.&nbsp;<\/li>\n\n\n\n<li>Both substances impair axonal transport \u2192 contribute to the&nbsp;<strong>neurotoxic side effect<\/strong>&nbsp;with.&nbsp;<\/li>\n\n\n\n<li>Additional inhibition of&nbsp;<strong>DNA and RNA synthesis<\/strong>&nbsp;(secondary effect).<\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"PTM\"><span class=\"ez-toc-section\" id=\"Phyto-Therapiemoglichkeiten\"><\/span>Phyto-therapy options<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">All references are from the NIH National Library of Medicine of the 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>, or recognized publishers. Care was taken to ensure that there were no conflicts of interest in order to guarantee a largely objective, scientifically sound level.<br>The articles may only contain abstracts. However, full texts are usually linked at the top right, either as free or fee-based publications.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Commonly known radioprotective agents include<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Huaier-Pilz_Trametes_robiniophila_Murr\"><\/span><strong>Huaier's mushroom (Trametes robiniophila Murr.)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The Huaier mushroom has been used in traditional Chinese medicine (TCM) for centuries and is gaining increasing attention in complementary cancer therapy. Studies indicate that huaier extracts can&nbsp;<strong>Support immune function<\/strong>,&nbsp;<strong>Reducing the side effects of radiotherapy<\/strong>&nbsp;and that&nbsp;<strong>Reducing the risk of recurrence<\/strong>&nbsp;can.<br>Particularly relevant is its effect on the&nbsp;<strong>Protective function of the bone marrow<\/strong>&nbsp;and the&nbsp;<strong>Stimulation of immune cells<\/strong>, which is of great importance in radiotherapy, as radiation can damage the bone marrow and impair blood formation.<br>The mushroom contains bioactive polysaccharides and peptidoglycans, which have an immunomodulating and anti-tumor effect.<br><br>It should be noted that the percentage of <a href=\"https:\/\/nutrimentas-shop.de\/products\/vitalpilz-huaier-trametes-robiniophila-fur-wissenschaftliche-zwecke\" target=\"_blank\" rel=\"noreferrer noopener\">Polysaccharides 32%<\/a> the content of \u03b2-glucan fractions should also be determined using <a href=\"https:\/\/cdn.shopify.com\/s\/files\/1\/0699\/3782\/4012\/files\/Phytolab_Beta_Glucane.pdf?v=1771581121\" target=\"_blank\" rel=\"noreferrer noopener\">Laboratory analysis<\/a> is proven to be around 47%, as both are the main active ingredients for which the effects proven by studies are also present!<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben\"><\/span><strong>Sources<\/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 June 3, 2024 - <a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S175646462400269X\" target=\"_blank\" rel=\"noopener\">The potential therapeutic benefits of Huaier in digestive system cancer: Its chemical components, pharmacological applications and future direction<\/a><br>- Hongrong Long, Zhngcai Wu - Front Immunol. 2023 Jun 28 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/37449208\/\" target=\"_blank\" rel=\"noopener\">Immunoregulatory effects of Huaier (Trametes robiniophila Murr) and relevant clinical applications<\/a><br>- Qu P, Han J, Qiu Y, Yu H, Hao J, Jin R, Zhou F. - Biomed Pharmacother. 2019 Sep - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31202171\/\" target=\"_blank\" rel=\"noopener\">Huaier extract enhances the treatment efficacy of imatinib in Ik6(+) Ph(+) acute lymphoblastic leukemia.<\/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\">Known as the \u201emushroom of immortality\u201c, Reishi has the following effects<strong>immunomodulating<\/strong>,&nbsp;<strong>anti-inflammatory<\/strong>&nbsp;and&nbsp;<strong>protects the liver<\/strong>.<br>It can increase stress resistance and support regeneration after radiation damage.<br>Triterpenes and beta-glucans promote the activity of macrophages and NK cells.<br><\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-2\"><\/span><strong>Sources<\/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\">Ganoderma lucidum spore oil induces apoptosis of breast cancer cells in vitro and in vivo by activating caspase-3 and caspase-9<\/a><br>- Lihua Chen, Abudumijiti Abulizi, Min Li - November 28, 2019 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31777016\/\" target=\"_blank\" rel=\"noreferrer noopener\">Protective Effect of Ganoderma (Lingzhi) on Radiation and Chemotherapy<\/a><br>- Xirui He, Xiaoxiao Wang, Jiacheng Fang, Yu Chang, Ning Ning, Hao Guo, Linhong Huang, Xiaoqiang Huang,<br>Zefeng Zhao - April 06, 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;(Reishi mushroom) for cancer treatment<\/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\">Cytotoxic action of Ganoderma lucidum on interleukin-3 dependent lymphoma DA-1 cells: involvement of apoptosis proteins<\/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 causes apoptosis in leukemia, lymphoma and multiple myeloma cells.<\/a><br>- Dr. med. Silke Fischer - December 11, 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\">The medicinal mushroom Ganoderma lucidum (Reishi) in modern medicine: An evidence-based review article for the professional audience<\/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\">Contains lentinan and beta-glucans, which&nbsp;<strong>Immune cell activity<\/strong>&nbsp;such as NK cells and macrophages.<br>Studies show a&nbsp;<strong>antimicrobial and antiviral effect<\/strong>, which is helpful for infectious risks after radiotherapy.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-3\"><\/span><strong>Sources<\/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 - March 14, 2007 - <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18202543\" target=\"_blank\" rel=\"noreferrer noopener\">A Phase I study of the safety of the nutritional supplement, active hexose correlated compound, AHCC, in healthy volunteers<\/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 - March 18, 2002 - <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/12076865\" target=\"_blank\" rel=\"noreferrer noopener\">Improved prognosis of postoperative hepatocellular carcinoma patients when treated with functional foods: a prospective cohort study<\/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\">Efficacy of orally administered superfine dispersed lentinan for advanced pancreatic cancer<\/a> <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19453066\" target=\"_blank\" rel=\"noreferrer noopener\">Source 4<\/a><br>- <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/18670743\/\" target=\"_blank\" rel=\"noreferrer noopener\">Clinical application of a combination therapy of lentinan, multi-electrode RFA and TACE in HCC<\/a> <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18670743\" target=\"_blank\" rel=\"noreferrer noopener\">Source 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\">Rich in beta-glucans, which&nbsp;<strong>Strengthen immune defenses<\/strong>&nbsp;and the&nbsp;<strong>Promote cell regeneration<\/strong>.<br>Studies indicate a role in the&nbsp;<strong>Blood sugar regulation<\/strong>&nbsp;and&nbsp;<strong>Weight management<\/strong>&nbsp;important aspects of nutrition during and after radiotherapy.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-4\"><\/span><strong>Sources<\/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\">The biological activities of the antitumor drug Grifola frondosa polysaccharide<\/a><br>- Xirui He, Xiaoxiao Wang, Jiacheng Fang, Yu Chang, Ning Ning, Hao Guo, Linhong Huang, Xiaoqiang Huang,&nbsp;<br>Zefeng Zhao - April 6, 2017 - International Journal of Biological Macromolecules - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/28366857\/\" target=\"_blank\" rel=\"noreferrer noopener\">Polysaccharides in Grifola frondosa mushroom and their health promoting properties: A review.<\/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\">Often used as&nbsp;<strong>Accompanying therapy for chemotherapy and radiotherapy<\/strong>&nbsp;used.<br>He&nbsp;<strong>improves the quality of life<\/strong>,&nbsp;<strong>strengthens the immune system<\/strong>&nbsp;and increases the&nbsp;<strong>Radiosensitivity of cancer cells<\/strong> (the response to radiation, - <strong>However, radiosensitivity varies greatly between different tumor types and even within a tumor<\/strong>.<br>The ingredient&nbsp;<strong>PSK (polysaccharide crestin)<\/strong>&nbsp;has been well studied clinically.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-5\"><\/span><strong>Sources<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">- Habtemariam S. Biomedicines. - 2020 May 25 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32466253\/\" target=\"_blank\" rel=\"noopener\">Trametes versicolor (Synn. Coriolus versicolor) Polysaccharides in Cancer Therapy: Targets and Efficacy<\/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 and its bioactive molecule are potential immunomodulators against cancer cell metastasis via inactivation of MAPK pathway<\/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\">Coriolus (Trametes) versicolor mushroom to reduce adverse effects from chemotherapy or radiotherapy in people with colorectal cancer<\/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\">Cytotoxic activities of Coriolus versicolor (Yunzhi) extract on human leukemia and lymphoma cells by induction of apoptosis<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Berberin_Berberis_vulgaris\"><\/span><strong>Barbary<\/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>Radiotherapy damage<\/strong>Preclinical and initial clinical studies indicate that berberine has radioprotective properties, particularly through antioxidant and anti-inflammatory effects. A pilot study showed a reduction in radiation-related side effects in cancer patients.&nbsp;<\/li>\n<\/ul>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Lymphomas<\/strong>In vitro and animal studies show that berberine can inhibit the growth of lymphoma cells, e.g. by suppressing the CD47 immune escape mechanism in diffuse large B-cell lymphoma. Synergistic effects with chemotherapeutic agents have also been observed.<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-6\"><\/span><strong>Sources<\/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 Aug - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40699408\/\" target=\"_blank\" rel=\"noopener\">Berberine as a natural immunomodulator of B lymphocytes<\/a><br>- Cao YQ, Sun C, Li JY, Zhou X. - Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2024 Apr - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/38660879\/\" target=\"_blank\" rel=\"noopener\">Research Progress on the Role of&nbsp;<strong>Berberine<\/strong>&nbsp;in Hematologic Malignancies and Its Related Mechanisms -Review<\/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, a novel compound in the therapy of diffuse large B-cell lymphoma via the B cell receptor signaling pathway<\/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\">Berberine exerts anti-tumor activity in diffuse large B-cell&nbsp;<strong>lymphoma<\/strong>&nbsp;by modulating c-myc\/CD47 axis<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Echinacea_Sonnenhut\"><\/span><strong>Echinacea (coneflower)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Strengthens the&nbsp;<strong>Innate immunity<\/strong>&nbsp;by stimulating phagocytes and NK cells.<br>Often used for colds and as part of therapies for&nbsp;<strong>Defense against infections<\/strong>&nbsp;used.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-7\"><\/span><strong>Sources<\/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\">Echinacea purpurea ameliorates bleomycin-induced pulmonary fibrosis in rats through modulating NADPH oxidase-4 and endothelin-1\/connective tissue growth factor\/matrix metalloproteinases signaling axis.<\/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\">Antioxidant and immuno-enhancing effects of 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 - Dose Response 2023 Jun 21 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/37359126\/\" target=\"_blank\" rel=\"noopener\">Immuno-Biochemical Impacts of Gamma Irradiation in Male Rats: A Dose-Response Study<\/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\">Biological effects of Echinacea purpurea on human blood cells<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Kurkuma_Curcumin\"><\/span><strong>Turmeric (curcumin)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Effective&nbsp;<strong>anti-inflammatory<\/strong>,&nbsp;<strong>antioxidant<\/strong>&nbsp;and&nbsp;<strong>protects cells from oxidative stress<\/strong>, which is caused by radiation.<br>Curcumin can improve the&nbsp;<strong>Support cell regeneration<\/strong>&nbsp;and the&nbsp;<strong>Enhancing the effect of radiotherapy<\/strong>, without damaging healthy cells.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-8\"><\/span><strong>Sources<\/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 Dec - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40671673\/\" target=\"_blank\" rel=\"noopener\">Ginger-derived vesicle-like nanoparticles loaded with curcumin to alleviate ionizing radiation-induced intestinal damage via gut microbiota regulation<\/a><br>- Xiu Z, Sun T, Yang Y, He Y, Yang S, Xue X, Yang W. - Oxid Med Cell Longev. 2022 Oct 4 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/36238646\/\" target=\"_blank\" rel=\"noopener\">Curcumin Enhanced Ionizing Radiation-Induced Immunogenic Cell Death in Glioma Cells through Endoplasmic Reticulum Stress Signaling Pathways<\/a><br>- Jagetia GC. - int J Radiat Biol. 2021 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33464136\/\" target=\"_blank\" rel=\"noopener\">Antioxidant activity of curcumin protects against the radiation-induced micronuclei formation in cultured human peripheral blood lymphocytes exposed to various doses of gamma-radiation<\/a><br><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Ingwer_Gingerole\"><\/span><strong>Ginger (gingerols)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Has&nbsp;<strong>antimicrobial and anti-inflammatory properties<\/strong>.<br>Supports digestion and can improve&nbsp;<strong>Mitigating the side effects of therapies<\/strong>.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-9\"><\/span><strong>Sources<\/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 Feb - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41237471\/\" target=\"_blank\" rel=\"noopener\">Dual-targeted exosome nanoplatform co-delivering doxorubicin and Fuzi Lizhong Tang bioactives for synergistic DLBCL therapy and chemotherapy-induced diarrhea management.<\/a><br>- Nafees S, Zafaryab M, Mehdi SH, Zia B, Rizvi MA, Khan MA. - Anticancer Agents Med Chem. 2021 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32951584\/\" target=\"_blank\" rel=\"noopener\">Anti-Cancer Effect of Gingerol in Cancer Prevention and Treatment<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Zitrusfruchte_Quercetin\"><\/span><strong>Citrus fruits &amp; quercetin<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Quercetin from onions and citrus fruits shows&nbsp;<strong>Antiviral and immunomodulating effect<\/strong>.<br>Studies investigate its role in the&nbsp;<strong>Strengthening the immune system<\/strong> (also in the context of&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>Sources<\/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\">Quercetin-derived microbial metabolite DOPAC potentiates CD8(+) T cell anti-tumor immunity via NRF2-mediated mitophagy<\/a><br>- Soofiyani SR, Hosseini K, Forouhandeh H, Ghasemnejad T, Tarhriz V, Asgharian P, Reiner \u017d, Sharifi-Rad J, Cho WC. - Oxide Med Cell Longev. 2021 Aug 2 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34381559\/\" target=\"_blank\" rel=\"noopener\">Quercetin as a Novel Therapeutic Approach for Lymphoma<\/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\">Quercetin induces apoptosis and autophagy in primary effusion lymphoma cells by inhibiting PI3K\/AKT\/mTOR and STAT3 signaling pathways<\/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\">Quercetin potentiates the antitumor activity of rituximab in diffuse large B-cell lymphoma by inhibiting STAT3 pathway<\/a><\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Schwarzkummelol_Nigella_sativa\"><\/span><strong>Black cumin seed oil (Nigella sativa)<\/strong><br><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Has been used as an immune booster since time immemorial.<br>The contained&nbsp;<strong>Thymoquinones<\/strong>&nbsp;work&nbsp;<strong>Antioxidant, anti-inflammatory and immunomodulating<\/strong>.<br>Shows positive effects on blood sugar, blood lipid levels and the immune system.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-11\"><\/span><strong>Sources<\/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\">Apoptotic Effect of Nigella sativa on Human Lymphoma U937 Cells<\/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\">Antitumor principles from Nigella sativa seeds<\/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\">Acts as&nbsp;<strong>Adaptogen<\/strong>, improves the&nbsp;<strong>Stress resistance<\/strong>&nbsp;and supports the&nbsp;<strong>Energy generation<\/strong>&nbsp;after therapies.<br>Can the&nbsp;<strong>Stabilize immune function<\/strong>&nbsp;and the&nbsp;<strong>Promote regeneration<\/strong>.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Quellenangaben-12\"><\/span><strong>Sources<\/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 May 19 - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/37205671\/\" target=\"_blank\" rel=\"noopener\">Ginsenoside 24-OH-PD from red&nbsp;<strong>ginseng<\/strong>&nbsp;inhibits acute T-lymphocytic leukaemia by activating the mitochondrial pathway<\/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\">Prospective Cohort Study of Ginseng Consumption in Association with Cancer Risk: Shanghai Women's Health Study<\/a><br>- Lee SY, Shin YW, Hahm KB. - J Dig Dis. 2008 Aug - <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/18956590\/\" target=\"_blank\" rel=\"noopener\">Phytoceuticals: mighty but ignored weapons against Helicobacter pylori infection<\/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>Phyto-therapeutics - signaling pathways<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\">The active ingredients of the Huaier mushroom - in particular polysaccharides, proteoglycans and flavonoids - intervene in several central signaling pathways:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>PI3K\/Akt\/mTOR<\/strong><br>Inhibition of this growth and survival pathway \u2192 reduces proliferation and induction of apoptosis in cancer cells<\/li>\n\n\n\n<li><strong>MAPK\/ERK and p38<\/strong><br>Modulation of these pathways \u2192 influences cell proliferation, differentiation and stress response<\/li>\n\n\n\n<li><strong>TLR4\/NF-\u03baB<\/strong><br>Activation via polysaccharides \u2192 stimulates immune cells (e.g. dendritic cells, macrophages) \u2192 improves immune response<\/li>\n\n\n\n<li><strong>AMPK<\/strong><br>Activation \u2192 promotes cellular energy balance and inhibits anabolic processes<\/li>\n\n\n\n<li><strong>YAP1 and Wnt\/\u03b2-catenin<\/strong><br>Inhibition of oncogenic signaling pathways \u2192 reduces tumor growth and tumor stem cell properties<\/li>\n\n\n\n<li><strong>TGF-\u03b2\/Smad<\/strong><br>Modulation \u2192 inhibits fibrotic processes in organs<\/li>\n\n\n\n<li><strong>Apoptosis<\/strong>-<br>Induction via&nbsp;<strong>Caspase-3\/9<\/strong>,&nbsp;<strong>ROS increase<\/strong>&nbsp;and&nbsp;<strong>mTOR inhibition<\/strong><\/li>\n\n\n\n<li><strong>Autophagy<\/strong><br>Promotion via mTOR inhibition and ROS \u2192 contributes to detoxification (e.g. of spike proteins)<\/li>\n\n\n\n<li><strong>EMT (Epithelial-Mesenchymal Transition)<\/strong><br>Escapement via&nbsp;<strong>Snail and MMP-9 downregulation<\/strong>&nbsp;\u2192 Reduces metastasis<\/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>Immunomodulation<\/strong><br>Polysaccharides (e.g. \u03b2-glucans) bind to&nbsp;<strong>Dectin-1<\/strong>,&nbsp;<strong>TLRs<\/strong>&nbsp;and&nbsp;<strong>Complement receptor 3<\/strong>&nbsp;\u2192 activate&nbsp;<strong>NF-\u03baB<\/strong>&nbsp;and&nbsp;<strong>MAPK<\/strong>&nbsp;\u2192 promote differentiation and activation of macrophages, dendritic cells and NK cells<\/li>\n\n\n\n<li><strong>Inflammation inhibition<\/strong><br>Triterpenes inhibit&nbsp;<strong>NF-\u03baB<\/strong>&nbsp;and that&nbsp;<strong>NLRP3-Inflammasome<\/strong>&nbsp;\u2192 reduce production of pro-inflammatory cytokines (TNF-\u03b1, IL-1\u03b2, IL-6)<\/li>\n\n\n\n<li><strong>Neuroprotection<\/strong><br>Inhibition of neuroinflammation, modulation of microglia, upregulation of&nbsp;<strong>BDNF<\/strong>&nbsp;\u2192 promotes neuroplasticity; activation of the&nbsp;<strong>FGFR1 signaling pathway<\/strong>&nbsp;\u2192 Increases neurogenesis in the hippocampus<\/li>\n\n\n\n<li><strong>Gut-brain axis<\/strong><br>Reishi modulates the microbiome \u2192 increases&nbsp;<strong>Bifidobacterium<\/strong>&nbsp;\u2192 improves tryptophan metabolism \u2192 increases&nbsp;<strong>Serotonin (5-HT)<\/strong>&nbsp;in the hypothalamus \u2192 sleep-promoting and mood-regulating<\/li>\n\n\n\n<li><strong>AMPK activation<\/strong><br>Regulates energy metabolism, promotes glucose uptake, improves insulin sensitivity (analogous to metformin)<\/li>\n\n\n\n<li><strong>Antihypertensive<\/strong><br>Inhibit peptides&nbsp;<strong>ACE<\/strong>&nbsp;and activate the&nbsp;<strong>eNOS\/NO\/cGMP signaling pathway<\/strong>&nbsp;\u2192 leads to vasodilation<\/li>\n\n\n\n<li><strong>Antidiabetic<\/strong><br>Activated&nbsp;<strong>AMPK<\/strong>, improves phosphorylation of&nbsp;<strong>IR<\/strong>,&nbsp;<strong>IRS1<\/strong>&nbsp;and&nbsp;<strong>Act<\/strong>&nbsp;\u2192 Increases insulin sensitivity; inhibits&nbsp;<strong>SREBP1c<\/strong>,&nbsp;<strong>FAS<\/strong>,&nbsp;<strong>SCD1<\/strong>&nbsp;\u2192 suppresses lipogenesis<\/li>\n\n\n\n<li><strong>Antioxidant<\/strong><br>Reduces ROS via activation of endogenous antioxidant systems<\/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>Immunomodulation<\/strong><br>The polysaccharide&nbsp;<strong>Lentinan<\/strong>&nbsp;binds to&nbsp;<strong>Dectin-1<\/strong>,&nbsp;<strong>TLRs<\/strong>&nbsp;and&nbsp;<strong>Complement receptor 3<\/strong>&nbsp;\u2192 activated&nbsp;<strong>NF-\u03baB<\/strong>&nbsp;and&nbsp;<strong>MAPK<\/strong>&nbsp;\u2192 Stimulates macrophages, dendritic cells and NK cells<\/li>\n\n\n\n<li><strong>Cytokine production<\/strong><br>Lentinan induced&nbsp;<strong>Interleukin-1 (IL-1)<\/strong>,&nbsp;<strong>Interleukin-2 (IL-2)<\/strong>,&nbsp;<strong>Interferon-\u03b3<\/strong>&nbsp;and&nbsp;<strong>TNF-\u03b1<\/strong>&nbsp;\u2192 enhances cellular immune response and apoptosis of tumor cells<\/li>\n\n\n\n<li><strong>Antitumor effect<\/strong><br>Lentinan has&nbsp;<strong>No direct cytotoxicity<\/strong>, but indirectly strengthens the fight against tumors via immune activation \u2192 increases&nbsp;<strong>Antibody production<\/strong>&nbsp;and&nbsp;<strong>endogenous interferon<\/strong><\/li>\n\n\n\n<li><strong>Apoptosis induction<\/strong><br>Promotes apoptosis of cancer cells via&nbsp;<strong>Caspase-3\/8\/9<\/strong>-Activation and mitochondrial signaling pathways<\/li>\n\n\n\n<li><strong>Antiviral<\/strong><br>Increases resistance to viruses (e.g. influenza) via interferon induction<\/li>\n\n\n\n<li><strong>Lipid metabolism<\/strong><br>The ingredient&nbsp;<strong>Eritadenin<\/strong>&nbsp;activated&nbsp;<strong>Lipoprotein receptors in the liver<\/strong>&nbsp;\u2192 increases LDL uptake \u2192 lowers LDL and VLDL cholesterol<\/li>\n\n\n\n<li><strong>Anti-inflammatory<\/strong><br>Inhibits&nbsp;<strong>NF-\u03baB<\/strong>&nbsp;and&nbsp;<strong>NLRP3-Inflammasome<\/strong>&nbsp;\u2192 Reduces inflammation<\/li>\n\n\n\n<li><strong>Microbiome regulation<\/strong><br>Promotes the growth of&nbsp;<strong>Bifidobacteria<\/strong>&nbsp;and&nbsp;<strong>Lactobacteria<\/strong>&nbsp;\u2192 Improves intestinal barrier and immunological regulation<\/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>Immunomodulation<\/strong><br>Polysaccharides (e.g. D-fraction, Grifolan) bind to&nbsp;<strong>TLR4<\/strong>,&nbsp;<strong>Dectin-1<\/strong>&nbsp;and&nbsp;<strong>Complement receptor 3<\/strong>&nbsp;\u2192 activate&nbsp;<strong>TLR4-MyD88-IKK\u03b2-NF-\u03baB p65-Signalweg<\/strong>&nbsp;\u2192 stimulate macrophages, dendritic cells, NK cells and cytotoxic T cells<\/li>\n\n\n\n<li><strong>TH1\/TH2 balance<\/strong><br>Shift from TH2 to TH1 response \u2192 increased production of&nbsp;<strong>Interferon-\u03b3<\/strong>,&nbsp;<strong>IL-12<\/strong>,&nbsp;<strong>IL-18<\/strong>&nbsp;\u2192 Strengthens cellular immune defense<\/li>\n\n\n\n<li><strong>Antitumor effect<\/strong><br>Induction of&nbsp;<strong>Apoptosis<\/strong>&nbsp;about the&nbsp;<strong>mitochondrial signaling pathway<\/strong>&nbsp;(Caspase-3\/9 activation) \u2192 Tumor cell death<\/li>\n\n\n\n<li><strong>MAPK signaling pathway<\/strong><br>Activate maitake polysaccharides&nbsp;<strong>p38 MAPK<\/strong>&nbsp;and&nbsp;<strong>JNK<\/strong>&nbsp;\u2192 Promote immune response and protect against immunosuppression<\/li>\n\n\n\n<li><strong>Blood sugar regulation<\/strong><br>Inhibition of the&nbsp;<strong>Alpha-glucosidase<\/strong>&nbsp;\u2192 Slows down glucose release; increases the&nbsp;<strong>Insulin sensitivity<\/strong>&nbsp;via F2\/F3 polysaccharides and SX glycoprotein.&nbsp;<\/li>\n\n\n\n<li><strong>Metabolism<\/strong><br>Activation of&nbsp;<strong>PPAR\u03b4<\/strong>&nbsp;and insulin-independent signaling pathways \u2192 improve glucose tolerance, lower triglycerides and cholesterol<\/li>\n\n\n\n<li><strong>Blood pressure regulation<\/strong><br>Influence on the&nbsp;<strong>Renin-angiotensin system<\/strong>&nbsp;\u2192 Lowering of the systolic blood pressure<\/li>\n\n\n\n<li><strong>Intestinal health<\/strong><br>Modulation of the&nbsp;<strong>Intestinal microbiota<\/strong>&nbsp;\u2192 Increase from&nbsp;<strong>Bifidobacteria<\/strong>&nbsp;and&nbsp;<strong>short-chain fatty acids<\/strong>&nbsp;\u2192 Anti-inflammatory and metabolically stabilizing<\/li>\n\n\n\n<li><strong>Antioxidant<\/strong><br>Activation of endogenous enzymes (SOD, glutathione peroxidase) \u2192 reduces oxidative stress<\/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>Immunomodulation<\/strong><br>Polysaccharide peptides (PSP, PSK) bind to&nbsp;<strong>TLRs<\/strong>&nbsp;(e.g. TLR2, TLR4),&nbsp;<strong>Dectin-1<\/strong>&nbsp;and&nbsp;<strong>Complement receptor 3<\/strong>&nbsp;\u2192 activate&nbsp;<strong>NF-\u03baB<\/strong>&nbsp;and&nbsp;<strong>p38 MAPK<\/strong>&nbsp;\u2192 Stimulate macrophages, dendritic cells, NK cells and T cells&nbsp;<\/li>\n\n\n\n<li><strong>Cytokine production<\/strong><br>Induction of&nbsp;<strong>IL-2<\/strong>,&nbsp;<strong>IFN-\u03b3<\/strong>,&nbsp;<strong>TNF-\u03b1<\/strong>&nbsp;and&nbsp;<strong>IL-6<\/strong>&nbsp;\u2192 strengthens cellular immune response<\/li>\n\n\n\n<li><strong>Antitumor effect<\/strong><br>Indirectly via immune activation; directly through&nbsp;<strong>Cell cycle arrest<\/strong>&nbsp;and&nbsp;<strong>Apoptosis induction<\/strong>&nbsp;in tumor cells (e.g. via caspase activation)<\/li>\n\n\n\n<li><strong>Anti-inflammatory<\/strong><br>Modulation of the&nbsp;<strong>TLR4-MyD88-NF-\u03baB signaling pathway<\/strong>&nbsp;\u2192 Regulates inflammatory response<\/li>\n\n\n\n<li><strong>Inhibition of metastases<\/strong><br>PSK inhibits&nbsp;<strong>Metalloproteinases (MMPs)<\/strong>&nbsp;\u2192 Reduces tumor invasion<\/li>\n\n\n\n<li><strong>Liver protection<\/strong><br>PSP increased&nbsp;<strong>GSH\/GSSG ratio<\/strong>&nbsp;\u2192 Antioxidant protection of hepatotoxic damage<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Berberin_Berberis_vulgaris-2\"><\/span><strong>Barbary<\/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>Apoptosis induction<\/strong><br>Activated&nbsp;<strong>p53<\/strong>,&nbsp;<strong>Caspase-3\/9<\/strong>,&nbsp;<strong>Cytochrome c<\/strong>; inhibits anti-apoptotic proteins such as&nbsp;<strong>Bcl-2<\/strong>&nbsp;and&nbsp;<strong>Mcl-1<\/strong><\/li>\n\n\n\n<li><strong>Cell cycle arrest<\/strong><br>Blocks G1 and G2\/M phase through upregulation of&nbsp;<strong>p21<\/strong>&nbsp;and&nbsp;<strong>GADD153<\/strong><\/li>\n\n\n\n<li><strong>Inhibition of growth pathways<\/strong><br>Inhibited&nbsp;<strong>PI3K\/Akt\/mTOR<\/strong>,&nbsp;<strong>MAPK<\/strong>,&nbsp;<strong>NF-\u03baB<\/strong>,&nbsp;<strong>STAT3<\/strong>&nbsp;and&nbsp;<strong>Wnt\/\u03b2-catenin<\/strong><\/li>\n\n\n\n<li><strong>Mitochondrial effect<\/strong><br>Disturbs membrane potential \u2192&nbsp;<strong>ROS increase<\/strong>&nbsp;\u2192 Energy crisis in tumor cells<\/li>\n\n\n\n<li><strong>DNA interaction<\/strong><br>Binds directly to DNA and inhibits&nbsp;<strong>Topoisomerase I<\/strong><\/li>\n\n\n\n<li><strong>Inflammation inhibition<\/strong><br>Inhibits&nbsp;<strong>NF-\u03baB<\/strong>&nbsp;and pro-inflammatory cytokines (TNF-\u03b1, IL-6)<\/li>\n\n\n\n<li><strong>Antioxidant<\/strong><br>Activated&nbsp;<strong>Nrf2\/HO-1<\/strong>- and&nbsp;<strong>AMPK<\/strong>-signaling pathways \u2192 protects healthy cells<\/li>\n\n\n\n<li><strong>Immunomodulation<\/strong><br>Suppressed&nbsp;<strong>CD47<\/strong>&nbsp;(\u201eDon't-eat-me\u201c signal) \u2192 promotes phagocytosis of tumor cells<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Echinacea_Sonnenhut-2\"><\/span><strong>Echinacea (coneflower)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>CB2 receptor activation<\/strong><br>Alkylamides bind to cannabinoid receptor 2 (CB2) on immune cells \u2192 modulate immune response without psychoactive effects<\/li>\n\n\n\n<li><strong>cAMP-PKA signaling pathway<\/strong><br>CB2 activation increases cAMP \u2192 activates PKA \u2192 regulates NF-\u03baB and cytokine production<\/li>\n\n\n\n<li><strong>MAPK signaling pathways<\/strong><br>Activation of&nbsp;<strong>p38\/MAPK<\/strong>,&nbsp;<strong>JNK<\/strong>&nbsp;and&nbsp;<strong>ERK1<\/strong>&nbsp;\u2192 Influences cell proliferation, differentiation and inflammatory response<\/li>\n\n\n\n<li><strong>NF-\u03baB inhibition<\/strong><br>Through CB2 and TLR4 modulation \u2192 reduces pro-inflammatory cytokines (TNF-\u03b1, IL-1\u03b2, IL-6)<\/li>\n\n\n\n<li><strong>TLR4 antagonism<\/strong><br>Suppresses MyD88\/TRIF-dependent signaling pathways \u2192 reduces inflammation<\/li>\n\n\n\n<li><strong>JAK1\/STAT1 signaling pathway<\/strong><br>Induction of interferon-dependent genes \u2192 strengthens antiviral defense<\/li>\n\n\n\n<li><strong>Cytokine modulation<\/strong><br>Increase of IL-10 (anti-inflammatory), inhibition of IL-12 (pro-inflammatory) \u2192 promotes TH1\/TH2 balance<\/li>\n\n\n\n<li><strong>T-cell regulation<\/strong><br>Promoted&nbsp;<strong>Foxp3 expression<\/strong>&nbsp;in regulatory T cells \u2192 immunomodulatory effect<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Kurkuma_Curcumin-2\"><\/span><strong>Turmeric (curcumin)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Inhibition of NF-\u03baB<\/strong><br>Suppresses this central transcription factor \u2192 reduces inflammation, cell proliferation and apoptosis inhibition \u2192 lowers expression of COX-2, TNF-\u03b1, IL-6, IL-8, MMP-9<\/li>\n\n\n\n<li><strong>Activation of p53<\/strong><br>Increases the tumor suppressor p53 \u2192 promotes DNA repair and apoptosis<\/li>\n\n\n\n<li><strong>Regulation of the Bax\/Bcl-2 ratio<\/strong><br>Increases pro-apoptotic Bax, lowers anti-apoptotic Bcl-2 \u2192 promotes mitochondria-mediated apoptosis<\/li>\n\n\n\n<li><strong>Inhibition of mTOR<\/strong><br>Inhibits growth and proliferation \u2192 anticarcinogenic effect<\/li>\n\n\n\n<li><strong>Antiangiogenesis<\/strong><br>Inhibits VEGF \u2192 prevents the formation of new tumor vessels<\/li>\n\n\n\n<li><strong>Inhibition of MMP-9<\/strong><br>Reduces tissue degradation \u2192 inhibits invasion and metastasis<\/li>\n\n\n\n<li><strong>Inhibition of adhesion molecules (e.g. CD44)<\/strong><br>Impairs tumor cell adhesion and invasion<\/li>\n\n\n\n<li><strong>Activation of the Nrf2 signaling pathway<\/strong><br>Increases the body's own antioxidants \u2192 protects against oxidative stress<\/li>\n\n\n\n<li><strong>Modulation of cell cycle proteins<\/strong><br>Inhibits cyclin D1, p16, CDK inhibitors \u2192 arrest in the cell cycle<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Ingwer_Gingerole-2\"><\/span><strong>Ginger (gingerols)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>TRPV1 receptor activation<\/strong><br>Gingerols bind to the TRPV1 ion channel on immune cells \u2192 put neutrophil granulocytes on high alert \u2192 increased ROS production and CXCL8 secretion during bacterial stimulation<\/li>\n\n\n\n<li><strong>Inflammation inhibition<\/strong><br>Inhibition of&nbsp;<strong>NF-\u03baB<\/strong>,&nbsp;<strong>p38 MAPK<\/strong>&nbsp;and&nbsp;<strong>JNK<\/strong>&nbsp;\u2192 reduces expression of pro-inflammatory cytokines (TNF-\u03b1, IL-1\u03b2, IL-6, IL-8), COX-2 and PGE2<\/li>\n\n\n\n<li><strong>Antioxidant<\/strong><br>Increase in antioxidant enzymes (e.g. SOD), protection against mitochondrial damage<\/li>\n\n\n\n<li><strong>Antiemetic<\/strong><br>Effect via serotonergic and cholinergic signaling pathways in the vomiting center \u2192 relieves nausea<\/li>\n\n\n\n<li><strong>Metabolic effect<\/strong><br>Improves insulin sensitivity, promotes GLUT4-mediated glucose uptake \u2192 helpful for diabetes<\/li>\n\n\n\n<li><strong>Cartilage protection<\/strong><br>Inhibition of the p38\/JNK signaling pathway \u2192 reduces cartilage degradation in osteoarthritis<\/li>\n\n\n\n<li><strong>Apoptosis induction<\/strong><br>6-Shogaol induces apoptosis in inflamed synovial cells \u2192 anti-inflammatory effect<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Zitrusfruchte_Quercetin-2\"><\/span><strong>Citrus fruits &amp; quercetin<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>NF-\u03baB inhibition<\/strong><br>Blocks this central inflammatory switch \u2192 reduces TNF-\u03b1, IL-6, IL-1\u03b2, COX-2 and iNOS<\/li>\n\n\n\n<li><strong>Nrf2 activation<\/strong><br>Binds to antioxidant response elements (ARE) \u2192 increases expression of HO-1, NQO1, GCLC \u2192 strengthens endogenous antioxidant defense<\/li>\n\n\n\n<li><strong>MAPK modulation<\/strong><br>Inhibits p38, JNK and ERK \u2192 regulates inflammation, proliferation and apoptosis<\/li>\n\n\n\n<li><strong>JAK\/STAT inhibition<\/strong><br>Suppresses pro-inflammatory signal transmission<\/li>\n\n\n\n<li><strong>COX-1\/2 and LOX inhibition<\/strong><br>Reduces prostaglandin and leukotriene formation \u2192 anti-inflammatory<\/li>\n\n\n\n<li><strong>AMPK\/SIRT1 activation<\/strong><br>Improves mitochondrial metabolism, promotes autophagy, protects against oxidative stress<\/li>\n\n\n\n<li><strong>Mast cell stabilization<\/strong><br>Inhibits histamine and cytokine release (e.g. IL-8, TNF) \u2192 anti-allergic<\/li>\n\n\n\n<li><strong>NLRP3 inflammasome attenuation<\/strong><br>Suppresses IL-1\u03b2 production<\/li>\n\n\n\n<li><strong>Senolytic effect<\/strong><br>Promotes elimination of old, dysfunctional cells (senescence)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Schwarzkummelol_Nigella_sativa-2\"><\/span><strong>Black cumin seed oil (Nigella sativa)<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Nrf2\/ARE activation<\/strong><br>Increases antioxidant enzymes (HO-1, SOD, CAT) \u2192 protects against oxidative stress<\/li>\n\n\n\n<li><strong>NF-\u03baB inhibition<\/strong><br>Suppresses inflammation \u2192 reduces TNF-\u03b1, IL-6, IL-1\u03b2, COX-2, iNOS<\/li>\n\n\n\n<li><strong>PI3K\/Akt\/mTOR inhibition<\/strong><br>Inhibits growth and proliferation \u2192 anticarcinogenic effect<\/li>\n\n\n\n<li><strong>MAPK modulation<\/strong><br>Inhibits p38, JNK and ERK \u2192 regulates inflammation and apoptosis<\/li>\n\n\n\n<li><strong>AMPK\/SIRT1 activation<\/strong><br>Improves mitochondrial metabolism, promotes autophagy<\/li>\n\n\n\n<li><strong>Apoptosis induction<\/strong><br>Activates p53, Bax\/Bcl-2 ratio, caspases \u2192 cellular tumor death<\/li>\n\n\n\n<li><strong>COX-2 inhibition<\/strong><br>Reduces inflammatory mediators<\/li>\n\n\n\n<li><strong>JAK\/STAT inhibition<\/strong><br>Suppresses pro-inflammatory signal transmission<\/li>\n\n\n\n<li><strong>GABA increase<\/strong><br>Increases cerebral GABA levels \u2192 anticonvulsant, neuroprotective<\/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>HPA axis modulation<\/strong><br>Ginsenosides (e.g.&nbsp;<strong>Rd<\/strong>) dampen the stress-induced&nbsp;<strong>Cortisol production<\/strong>&nbsp;\u2192 adaptogenic effect for exhaustion and stress<\/li>\n\n\n\n<li><strong>Neurotransmitter systems<\/strong><br>Activate&nbsp;<strong>cholinergic<\/strong>&nbsp;and&nbsp;<strong>dopaminergic signaling pathways<\/strong>&nbsp;\u2192 improve cognitive performance, concentration and mood (e.g. through ginsenoside&nbsp;<strong>Rg1<\/strong>)<\/li>\n\n\n\n<li><strong>Inflammation inhibition<\/strong><br>Inhibit&nbsp;<strong>NF-\u03baB<\/strong>&nbsp;and proinflammatory cytokines \u2192 reduce neuroinflammatory processes<\/li>\n\n\n\n<li><strong>Antioxidant effect<\/strong><br>Activate&nbsp;<strong>Nrf2<\/strong>-signaling pathway \u2192 increase endogenous antioxidants (HO-1, SOD) \u2192 protect against oxidative stress<\/li>\n\n\n\n<li><strong>Neuroprotection<\/strong><br>Convey&nbsp;<strong>BDNF<\/strong>&nbsp;(brain-derived neurotrophic factor) \u2192 support neuronal regeneration and synaptic plasticity<\/li>\n\n\n\n<li><strong>Amyloid \u03b2-inhibition<\/strong><br>Suppress the formation of&nbsp;<strong>Amyloid-\u03b2 plaques<\/strong>&nbsp;\u2192 Potentially neuroprotective in Alzheimer's disease<\/li>\n\n\n\n<li><strong>Promoting blood circulation<\/strong><br>Increase the production of&nbsp;<strong>Nitric oxide (NO)<\/strong>&nbsp;\u2192 Vasodilation, improved cerebral and peripheral perfusion<\/li>\n\n\n\n<li><strong>Immunomodulation<\/strong><br>Regulate macrophage and NK cell activity via&nbsp;<strong>TLR4<\/strong>&nbsp;and&nbsp;<strong>MAPK<\/strong>&nbsp;\u2192 strengthen immune defense<\/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 - the history of development<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 - Development of the <strong>Hybridoma technology<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Before 1975, researchers were unable to find large quantities of <strong>identical antibody<\/strong> produce antibodies. When they immunized a mouse with an antigen, the mouse produced a limited number of different antibodies against different parts of the antigen (polyclonal).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Georges K\u00f6hler<\/strong> and <strong>C\u00e9sar Milstein<\/strong> developed the <strong>Hybridoma technology<\/strong> by<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>B lymphocytes from the spleen of an immunized mouse took<\/li>\n\n\n\n<li>these with <strong>immortal myeloma cells<\/strong> (cancer cells that can divide indefinitely) immunized with<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>That was revolutionary<\/strong>, which is why both were awarded the <strong>Nobel Prize for Physiology or Medicine<\/strong> received.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Wie_konnen_Zellen_unsterblich_sein\"><\/span>How can cells be immortal?<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Tumor cells are always immortal because they use a trick to stimulate the cell to divide again and again and maintain this ability to divide. Normal cells, on the other hand, die automatically, as explained below.<\/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>Plasmacytoma in mice - the original source<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The immortal myeloma cells originate from natural plasmacytomas (lymphoma tumors) in inbred mice, especially from BALB\/c mouse strains. These tumors developed spontaneously or were induced by oil injections.<\/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>The first common cell line - SP2\/0<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The first common cell line was SP2\/0 and was established in 1979. These cells were used by K\u00f6hler and Milstein to develop the first hybridoma technology.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Other important cell lines are:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>NSO (NSO\/U mouse myeloma)<\/li>\n\n\n\n<li>Ag8 (a mouse myeloma)<\/li>\n\n\n\n<li>P3\/NS1\/1-Ag4-1 (also mouse myeloma)<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Warum_sind_Myelomzellen_unsterblich\"><\/span>Why are myeloma cells immortal?<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>Normal cells - The Hayflick limit<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Normal cells can only divide 50-70 times (Hayflick limit, discovered in 1961). Then division stops and the cell dies. The reason for this is that the telomeres (ends of the chromosomes) become shorter with each division and after a certain shortness the cell dies (senescence), or apoptoses.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Visual:<\/strong><\/p>\n\n\n\n<pre class=\"wp-block-code\"><code>Normal cell (young)\n\u251c\u2500 Telomeres long\n\u251c\u2500 Cell divides 1x \u2192 telomeres shorter\n\u251c\u2500 Cell divides 2x \u2192 even shorter\n\u251c\u2500 ...\n\u251c\u2500 cell divides 50x \u2192 telomeres CRITICALLY short\n\u2514\u2500 STOP: cell dies (senescence)<\/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>Cancer cells are inventive - activate telomerase<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Cancer cells (such as myeloma cells) break free from this system:<\/p>\n\n\n\n<ol class=\"wp-block-list\">\n<li>Activation of telomerase, which rebuilds telomeres<\/li>\n\n\n\n<li>TP53 mutations (p53 inactivation) that switch off the tumor suppressor<\/li>\n\n\n\n<li>other survival signals.<\/li>\n<\/ol>\n\n\n\n<pre class=\"wp-block-code\"><code>Myeloma cell (tumor)\n\u251c\u2500 Telomerase activated \u2190 (this is the key!)\n\u251c\u2500 Cell divides 1x \u2192 Telomeres are REPAIRED\n\u251c\u2500 Cell divides 2x \u2192 Telomeres are repaired again\n\u251c\u2500 Cell divides 50x \u2192 Telomeres are still long\n\u251c\u2500 Cell divides 1000x \u2192 still alive\n\u2514\u2500 UNLIMITED divisions possible<\/code><\/pre>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Warum_Telomerase\"><\/span>Why telomerase?<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Telomerase is a ribonucleoprotein enzyme (consisting of TERT = Telomerase Reverse Transcriptase and TERC = Telomerase RNA Component). It repeatedly adds the sequence TTAGGG to the telomere ends and thus repairs the shortening caused by the division process, which leads to the immortality of the cell.<\/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>Telomerase is present in normal cells <strong>OFF<\/strong><\/li>\n\n\n\n<li>Only weakly present in germ cells (sperm, egg cells) and stem cells<\/li>\n\n\n\n<li>Therefore: Normal cells age and die<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>For cancer:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Telomerase is <strong>ON<\/strong> (85-95% of all cancer cells)<\/li>\n\n\n\n<li>Constant repair of telomeres<\/li>\n\n\n\n<li>Cell becomes \u201eimmortal\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>TP53 mutation - the other piece of the puzzle<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">But telomerase alone is not enough, the cell would still trigger a senescence checkpoint:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">When telomeres become critically short, TP53 (the \u201eguardian of the genome\u201c) is normally activated, which says: \u201eStop, the cell is damaged, let's die\u201c. In cancer cells, TP53 <strong>mutated<\/strong> <strong>or inactivated<\/strong>, so the cell ignores this command.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>This means:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Short telomeres \u2192 normally: p53 activated \u2192 cell death<\/li>\n\n\n\n<li>Myeloma cell: short telomeres \u2192 p53 is INACTIVE \u2192 cell says: \u201eNever mind\u201c \u2192 continue<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Wie_Myelomzellen_unsterblich_wurden\"><\/span>How myeloma cells became immortal<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The myeloma cells in mice developed in several steps over decades: <\/p>\n\n\n\n<ol class=\"wp-block-list\">\n<li>A normal plasma cell suffered a t(12;15) translocation or other genetic errors<\/li>\n\n\n\n<li>The MYC gene was overexpressed (cancer driver)<\/li>\n\n\n\n<li>p53 mutated<\/li>\n\n\n\n<li>Telomerase was activated,<\/li>\n\n\n\n<li>After many cycles of selective printing, true immortal cells were created.<\/li>\n<\/ol>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Die_erste_SP20_Hybridoma-Zelle\"><\/span>The first SP2\/0 hybridoma cell<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">SP2\/0 originates from a mouse myeloma. The myeloma was isolated from a BALB\/c mouse (probably after oil injection). The cells were then cultured and established. They have TELOMERASE active and defective p53.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The name is explained by:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>SP<\/strong>&nbsp;stands for&nbsp;<em>Spleen<\/em>&nbsp;(spleen), as the cells originate from spleen cells.&nbsp;<\/li>\n\n\n\n<li><strong>2<\/strong>&nbsp;refers to the second generation of the cell line.&nbsp;<\/li>\n\n\n\n<li><strong>0<\/strong>&nbsp;symbolizes the&nbsp;<strong>Loss of the HGPRT function<\/strong>&nbsp;(\u201ezero\u201c activity), which causes HAT sensitivity*.<br>* Sensitivity of cells to a&nbsp;<strong>HAT medium<\/strong>&nbsp;(hypoxanthine-aminopterin-thymidine), which is used for the selection of hybridomas<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>The criticism at the time:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>These cells are cancer cells themselves!<\/li>\n\n\n\n<li>In other words, \u201etumor cells\u201c are fused with normal B cells<\/li>\n\n\n\n<li>That was ethically\/practically worth considering<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>The solution:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>The cells were <strong>deliberately eradicated<\/strong> for antibody production<\/li>\n\n\n\n<li>They do produce immunoglobulins (because part of the B cell is inside), but no other \u201eharmful\u201c genes<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Warum_keine_normale_B-Zellen\"><\/span>Why no normal B cells?<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">B cells from the spleen (or blood) can only divide to a limited extent (Hayflick limit). After they have been fused with myeloma cells, the new \u201ehybridomas\u201c must also be able to divide indefinitely, otherwise they are useless.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>This means:<\/strong><\/p>\n\n\n\n<pre class=\"wp-block-code\"><code>Experiment 1: Only B cells from spleen\n\u251c\u2500 Produce antibodies (+)\n\u2514\u2500 Divide only 50x, then dead (-)\n\nExperiment 2: Myeloma cells only\n\u251c\u2500 Divide indefinitely (+)\n\u2514\u2500 Do not produce specific antibodies (-)\n\nExperiment 3: HYBRIDOMA (fusion)\n\u251c\u2500 Divide indefinitely (+) (from myeloma)\n\u251c\u2500 Produce antibodies (+) (from the B cell)\n\u2514\u2500 Perfect!  (+)<\/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>The fusion - the hybridoma process<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Fusion takes place using polyethylene glycol (PEG) or electrical pulses (electrofusion). PEG reinforces membrane adhesion: two cells fuse to form one cell with two nuclei. After cytokinesis (cytokinesis ensures that each daughter cell receives organelles and cytoplasm and can function as an independent cell): One cell with genetic material from both parent cells.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Visual:<\/strong><\/p>\n\n\n\n<pre class=\"wp-block-code\"><code>B cell (antibody producer)\n    +\nMyeloma cell (immortal)\n    \u2193 (PEG or electrofusion)\nHybridoma (both!)\n    \u251c\u2500 Immortal (from myeloma)\n    \u2514\u2500 Produces antibodies (from B cell)<\/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>Why myeloma cells and not other tumors?<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Myeloma cells (plasma cell lymphomas) were chosen because they:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>divide quickly (high proliferation rate)<\/li>\n\n\n\n<li>are genetically stable (not too many other mutations)<\/li>\n\n\n\n<li>can reject non-productive antibodies (selection pressure)<\/li>\n\n\n\n<li>are already specialized in protein secretion (produce antibodies)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Other types of cancer would not have worked, for example:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Prostate cancer - Not specialized in protein secretion<\/li>\n\n\n\n<li>Melanoma - too many other mutations<\/li>\n\n\n\n<li>Hepatocellular carcinoma - no antibody production<\/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>The paradox - cancer cells as a remedy for cancer<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The beauty and paradox of hybridoma technology: <strong>Cancer cells (myeloma) are used to produce drugs against cancer (lymphoma)!<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Myeloma cells are themselves a type of cancer, but by fusing with B cells they become a therapeutic production site for monoclonal antibodies.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Neuere_Alternativen\"><\/span>Newer alternatives<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Today, myeloma cells are used less frequently, but<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Humanized cell lines (e.g. CHO = Chinese Hamster Ovary cells)<\/li>\n\n\n\n<li>Display technologies (Phage Display, Yeast Display)<\/li>\n\n\n\n<li>In vitro mutagenesis instead of animal immunization.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Why the change?<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li> (+) No myeloma cell contamination<\/li>\n\n\n\n<li> (+) More direct than chimeric antibodies<\/li>\n\n\n\n<li> (+) Ethically cleaner<\/li>\n\n\n\n<li> (+) Faster<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">In 1990, the hybridoma technology with myeloma cells for rituximab was the <strong>only practical solution available<\/strong>.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Zusammenfassung-2\"><\/span>Summary<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>Question<\/th><th>Answer<\/th><\/tr><\/thead><tbody><tr><td><strong>Where did myeloma cells come from?<\/strong><\/td><td>Spontaneous or oil-induced lymphomas in mice<\/td><\/tr><tr><td><strong>Which line?<\/strong><\/td><td>SP2\/0, NSO, Ag8 (all mouse myeloma cell lines)<\/td><\/tr><tr><td><strong>Why immortal?<\/strong><\/td><td>Telomerase active + p53 mutated = Hayflick limit overcome<\/td><\/tr><tr><td><strong>How does telomerase work?<\/strong><\/td><td>TERT + TERC enzymes endlessly repair telomeres<\/td><\/tr><tr><td><strong>Why not just B cells?<\/strong><\/td><td>Would die after 50 divisions (Hayflick limit)<\/td><\/tr><tr><td><strong>Why not just myeloma?<\/strong><\/td><td>Would not produce antibodies<\/td><\/tr><tr><td><strong>Why fusion?<\/strong><\/td><td>Best of both worlds: immortality + antibody production<\/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 - Discovery of the surface protein CD20<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Lee Nadler<\/strong> from the <strong>Dana Farber Cancer Institute<\/strong> in Boston discovered the surface protein CD20 as a surface marker on B lymphocytes.<br>He used the new hybridoma technology to make antibodies against B cell markers. He identified CD20 as:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>A protein on the surface of all B cells<\/li>\n\n\n\n<li>Also present on B-cell lymphoma cells<\/li>\n\n\n\n<li>A potential therapeutic target<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Erstes_Experiment\"><\/span>First experiment<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">He tested a murine (mouse) anti-CD20 antibody on lymphoma patients. The result was weak, but it was the first proof-of-concept that CD20 targeting is possible.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Das_chimare_Antikorper-Problem\"><\/span>The chimeric antibody problem<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Nadler's antibody and other research teams had murine (mouse) antibodies against CD20, but there were two critical problems:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Problem 1: HAMA (Human Anti-Mouse Antibodies)<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>The human body recognized the mouse antibody as \u201eforeign\u201c<\/li>\n\n\n\n<li>The patient formed antibodies against the antibody<\/li>\n\n\n\n<li>After a few infusions, the mouse antibody was neutralized<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Problem 2: Poor effectiveness<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>The mouse Fc part (constant region) insufficiently activated the human immune system<\/li>\n\n\n\n<li>Mouse IgG does not bind optimally to human Fc receptors<\/li>\n\n\n\n<li>Mouse IgG does not optimally activate human complement<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>The solution<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Geneticists came up with the idea<strong> to combine the mouse part (variable region) with the human region (constant region):<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Variable region (Fab part)<\/strong> - Mouse<br>This is the part that recognizes CD20<br>Mouse antibodies have special gene segments that can recognize CD20 very specifically<\/li>\n\n\n\n<li><strong>Constant region (Fc part)<\/strong> - Human<br>This is the part that activates the immune system<br>Human Fc regions bind perfectly to human Fc receptors<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Result: the chimeric monoclonal antibody<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Specific enough (due to mouse recognition part)<\/li>\n\n\n\n<li>Effective enough (due to human effector function)<\/li>\n\n\n\n<li>Fewer HAMA problems (because more human)<\/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 - Rituximab development<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>The IDEC team<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">A biotech company called <strong>IDEC Pharmaceuticals<\/strong> (founded in 1990) began working on CD20 antibodies. They wanted to<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Find murine antibodies against CD20<\/li>\n\n\n\n<li>convert into chimeric antibodies<\/li>\n\n\n\n<li>test whether they work better than Nadler's previous attempts<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Entwicklung\"><\/span>Development<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>1. immunization of mice<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Mice were immunized with human B cell lines<\/li>\n\n\n\n<li>The mouse immune system recognized: \u201eThese are foreign cells, make antibodies against them!\u2018<\/li>\n\n\n\n<li>Hybridomas were obtained from the mouse splice cells by fusion with the myeloma cells<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>2. screening<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>The best was selected from thousands of hybridomas<\/li>\n\n\n\n<li>Which one recognizes CD20 very selectively?<\/li>\n\n\n\n<li>It should be a strong IgG1 antibody (the best isotype for ADCC and CDC)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>3. chimerization<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>The best murine antibody gene was taken<\/li>\n\n\n\n<li>The variable region (antigen-recognizing) remained murine<\/li>\n\n\n\n<li>The constant region (IgG1-Fc) was replaced by human<\/li>\n\n\n\n<li>Result: <strong>C2B8<\/strong> (chimeric antibody #2, B-cell antigen #8)<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>4. production<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>The rituximab gene was found in <strong>CHO cells<\/strong> (Chinese Hamster Ovary) inserted<\/li>\n\n\n\n<li>These cells produced Rituximab in bioreactors<\/li>\n\n\n\n<li>Batches could be cleaned for medical quality<\/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 - Clinical tests<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 - Phase I study<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The first paper on the clinical testing of 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\">Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20<\/a>\u201e<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">This study showed:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>15 patients with refractory B-cell lymphoma (not responding to standard chemotherapy)<\/li>\n\n\n\n<li>Rituximab was infused in doses of 10 to 500 mg\/m\u00b2<\/li>\n\n\n\n<li><strong>Result:<\/strong> 6 out of 15 patients (40%) had objective remissions<\/li>\n\n\n\n<li><strong>Side effects:<\/strong> Surprisingly mild for such an effective therapy<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>That was sensational<\/strong> - an antibody ALONE (without chemotherapy!) was effective against lymphoma!<\/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 - Phase II study<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">A larger study of 166 patients with refractory lymphoma:<\/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\">Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphomas: half of patients respond to a four-dose treatment program<\/a>\u201e<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Result:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>48% of the patients had objective remission<\/li>\n\n\n\n<li>Some had complete remissions that lasted a long time<\/li>\n\n\n\n<li>The response rate was higher than in historical data with chemotherapy alone<\/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 - FDA approval (November)<span class=\"ez-toc-section-end\"><\/span><\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">Based on the Phase I and Phase II data, IDEC submitted a <strong>Biologics License Application (BLA)<\/strong> with the FDA. On <strong>November 26, 1997<\/strong> Rituximab (under the name <strong>Rituxan<\/strong>) approved by the FDA.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>That was a milestone:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>First monoclonal antibody for oncology<\/strong><\/li>\n\n\n\n<li>Others came later (trastuzumab for breast cancer in 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>Why exactly this mouse antibody?<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">CD20 is a surface protein with a 3D structure recognized by the IDEC hybridoma antibody. Mouse immune systems have different V genes (variable region genes) than humans. This means that mouse antibodies can sometimes recognize structures that human antibodies do not.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Why wasn't a humanized antibody developed directly?<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">That was technically very difficult in 1990:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Humanization requires transplanting murine CDRs (Complementarity-Determining Regions) into human framework regions<\/li>\n\n\n\n<li>This was possible, but complex<\/li>\n\n\n\n<li>Chimeric antibodies were faster and more practical<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Fusion combines the best:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>From the B cell: ability to produce specific antibodies<\/li>\n\n\n\n<li>From myeloma: unlimited ability to divide<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Seit_1997\"><\/span>Since 1997<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Rituximab became standard treatment for non-Hodgkin's lymphoma<\/li>\n\n\n\n<li>Later approved for rheumatoid arthritis and other indications<\/li>\n\n\n\n<li>Biologists called it \u201e<strong>The first antibody miracle of modern medicine<\/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>Dosage recommendations<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\">All recommendations are to be considered exclusively as a basis for discussion with the treating physicians, in particular oncologists, and do not represent a generally valid dosage indication.<\/p>\n<\/blockquote>\n\n\n\n<h3 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Fur_ABC-DLBCL\"><\/span>For ABC-DLBCL<span class=\"ez-toc-section-end\"><\/span><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Dosages of Huaier are NOT generally dependent on body weight and therefore usually do not require adjustment, as the effect is not dependent on blood concentration (like antibiotics, for example), but rather addresses signaling pathways, thereby inducing the intended effects.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>FL with t(14;18)<\/strong><br>PI3K\/AKT-dominant \u2192 Huaier ideal <\/li>\n\n\n\n<li><strong>DLBCL-ABC<\/strong><br>NF-\u03baB-dominant \u2192 Huaier + curcumin ideal <\/li>\n\n\n\n<li><strong>DLBCL-GCB<\/strong><br>BCL2-dominant \u2192 similar to FL <\/li>\n\n\n\n<li><strong>Burkitt<\/strong><br>MYC-driven \u2192 mTOR inhibitors (sulforaphane, berberine)<\/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\">... will be continued ...<\/p>","protected":false},"excerpt":{"rendered":"<p><span class=\"span-reading-time rt-reading-time\" style=\"display: block;\"><span class=\"rt-label rt-prefix\">Reading time<\/span> <span class=\"rt-time\"> 78<\/span> <span class=\"rt-label rt-postfix\">minutes<\/span><\/span>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\/en\/blog\/2026\/03\/13\/lymphome-therapiemoeglichkeiten\/\" rel=\"bookmark\">Read More \"<span class=\"screen-reader-text\">Lymphoma - treatment options<\/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\/en\/wp-json\/wp\/v2\/posts\/12877","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/comments?post=12877"}],"version-history":[{"count":1,"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/posts\/12877\/revisions"}],"predecessor-version":[{"id":13625,"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/posts\/12877\/revisions\/13625"}],"wp:attachment":[{"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/media?parent=12877"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/categories?post=12877"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csiag.de\/en\/wp-json\/wp\/v2\/tags?post=12877"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}