{"entity":{"id":"splenic-marginal-zone-lymphoma","kind":"cancer","name":"Splenic marginal zone lymphoma","aka":["SMZL","Splenic lymphoma with villous lymphocytes","Splenic marginal zone B-cell lymphoma"],"tldr":"Splenic marginal zone lymphoma is a slow-growing lymphoma that grows in the spleen and bone marrow, causing a very large spleen and a raised lymphocyte count but rarely swollen lymph nodes. Many people need no treatment for years; when they do, rituximab has largely replaced removal of the spleen, and hepatitis C should be treated first where it is present.","summary":"WHO-HAEM5 keeps splenic marginal zone lymphoma as the splenic member of the marginal zone lymphoma family, defined by massive splenomegaly, moderate lymphocytosis with or without villous lymphocytes, marrow involvement, rare peripheral lymphadenopathy and an indolent course; with no randomised trials there is no formal standard of care, and splenectomy, done for many years, is no longer encouraged first-line because rituximab is as effective with less toxicity (Alaggio 2022; Rev Bras Hematol Hemoter 2017). Its genome carries recurrent NOTCH2, KLF2 and TP53 mutations, with TNFAIP3, KMT2D and TRAF3 also recurrent across 475 cases, though exome studies agree poorly with one another (Scientific Reports 2019). An association with hepatitis C virus is recognised in the ESMO guideline, which recommends antiviral therapy as first treatment in infected patients (Zucca 2020).\n\nHow it differs from its parent: it is diagnosed from blood, marrow and spleen rather than a tissue biopsy of an organ or node; it carries the NOTCH2 and KLF2 lesions the other marginal zone lymphomas mostly lack; and its differential diagnosis includes hairy cell leukaemia and the new WHO-HAEM5 category of splenic B-cell lymphoma/leukaemia with prominent nucleoli.\n\nHow common: no registry share in the sources read; rare.\n\nTreatment: watch and wait while asymptomatic; antiviral therapy for hepatitis C-associated disease; rituximab alone or with chemotherapy for symptomatic disease; splenectomy for selected patients; BTK inhibitors and lenalidomide-rituximab as on the parent page (Zucca 2020; Rev Bras Hematol Hemoter 2017).","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Splenic_marginal_zone_lymphoma","links":[{"label":"NCI PDQ: adult non-Hodgkin lymphoma treatment","url":"https://www.cancer.gov/types/lymphoma/patient/adult-nhl-treatment-pdq"},{"label":"Alaggio 2022, Leukemia: the 5th edition WHO classification of haematolymphoid tumours, lymphoid neoplasms","url":"https://doi.org/10.1038/s41375-022-01620-2"},{"label":"Zucca 2020, Annals of Oncology: marginal zone lymphomas, ESMO clinical practice guidelines","url":"https://doi.org/10.1016/j.annonc.2019.10.010"},{"label":"Rev Bras Hematol Hemoter 2017: splenic marginal zone lymphoma, review of diagnostic and therapeutic challenges","url":"https://doi.org/10.1016/j.bjhh.2016.09.014"},{"label":"Scientific Reports 2019: systematic review of somatic mutations in splenic marginal zone lymphoma, 475 cases","url":"https://doi.org/10.1038/s41598-019-46906-1"}],"tags":["subtype-page","wave4","haematologic","rare"],"related":["marginal-zone-lymphoma","malt-lymphoma","nodal-marginal-zone-lymphoma","hairy-cell-leukemia","splenic-b-cell-lymphoma-leukaemia-prominent-nucleoli"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["rituximab","bendamustine","zanubrutinib","lenalidomide"],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-tx-watch-and-wait","lymphoma-tx-pjp-and-infection-prophylaxis"],"trials":["augment"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"Rare; the systematic review of its mutations gathered 475 sequenced cases from fourteen studies (Scientific Reports 2019). The ESMO guideline treats it as the least common of the three marginal zone lymphomas; no registry share is in the sources read.","subtypes":["Splenic marginal zone lymphoma with villous lymphocytes","Hepatitis C-associated splenic marginal zone lymphoma","Splenic marginal zone lymphoma with NOTCH2 or KLF2 mutation","Transformed splenic marginal zone lymphoma (diffuse large B-cell)"],"biomarkers":["Villous lymphocytes and marrow intrasinusoidal infiltration","NOTCH2, KLF2 and TP53 mutations","Hepatitis C serology","Immunophenotype: CD20 positive, CD5, CD10, CD103 and annexin A1 negative"],"standardOfCare":[{"setting":"Asymptomatic","approach":"Watch and wait; antiviral therapy first if hepatitis C is present.","refs":["marginal-zone-lymphoma"]},{"setting":"Symptomatic","approach":"Rituximab alone or with chemotherapy; splenectomy for selected patients; BTK inhibitors or lenalidomide-rituximab later.","refs":["rituximab","bendamustine","zanubrutinib","lenalidomide","augment"]},{"setting":"Splenic marginal zone lymphoma: hepatitis C first, then rituximab, then splenectomy","approach":"An indolent disease of the spleen, marrow and blood. A patient with no symptoms, no cytopenias and a spleen that is not troublesome is watched, sometimes for years.\n\nWhen treatment is needed, the order is: test and treat hepatitis C if present, because direct-acting antivirals alone produce lymphoma remission in a proportion of hepatitis C-associated cases and that is a reason to check before giving any chemotherapy. Then rituximab alone, weekly for four to eight doses, which corrects cytopenias and shrinks the spleen in the large majority and has displaced splenectomy as first treatment. Chemoimmunotherapy with bendamustine and rituximab is used for disease that does not respond or that transforms.\n\nSplenectomy is now reserved for patients who cannot have rituximab, whose disease is confined to the spleen and who need a diagnosis, or who have refractory painful splenomegaly. It requires pneumococcal, Haemophilus influenzae type b and meningococcal vaccination at least two weeks beforehand where possible, and lifelong penicillin prophylaxis afterwards. Zanubrutinib has activity in relapsed disease across marginal zone subtypes.","refs":["rituximab","bendamustine","zanubrutinib","lymphoma-tx-watch-and-wait","lymphoma-tx-pjp-and-infection-prophylaxis","paper-magnolia-zanubrutinib-mzl-ccr-2021","paper-esmo-marginal-zone-lymphoma-zucca-ann-oncol-2020"],"guideline":{"version":"ESMO marginal zone lymphomas; NCCN B-Cell Lymphomas","url":"https://www.esmo.org/guidelines/esmo-clinical-practice-guidelines-haematological-malignancies"}}],"stateOfArt":[],"history":[],"pipeline":[],"openProblems":[],"parent":"marginal-zone-lymphoma"},"route":"/cancers/splenic-marginal-zone-lymphoma/","neighbours":{"cancer":[{"id":"malt-lymphoma","kind":"cancer","name":"Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)","route":"/cancers/malt-lymphoma/"},{"id":"hairy-cell-leukemia","kind":"cancer","name":"Hairy cell leukaemia","route":"/cancers/hairy-cell-leukemia/"},{"id":"marginal-zone-lymphoma","kind":"cancer","name":"Marginal zone lymphoma","route":"/cancers/marginal-zone-lymphoma/"},{"id":"nodal-marginal-zone-lymphoma","kind":"cancer","name":"Nodal marginal zone lymphoma","route":"/cancers/nodal-marginal-zone-lymphoma/"},{"id":"splenic-b-cell-lymphoma-leukaemia-prominent-nucleoli","kind":"cancer","name":"Splenic B-cell lymphoma/leukaemia with prominent nucleoli (formerly B-cell prolymphocytic leukaemia and hairy cell leukaemia variant)","route":"/cancers/splenic-b-cell-lymphoma-leukaemia-prominent-nucleoli/"}],"drug":[{"id":"bendamustine","kind":"drug","name":"Bendamustine","route":"/drugs/bendamustine/"},{"id":"lenalidomide","kind":"drug","name":"Lenalidomide","route":"/drugs/lenalidomide/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},{"id":"zanubrutinib","kind":"drug","name":"Zanubrutinib","route":"/drugs/zanubrutinib/"}],"term":[{"id":"cancer-related-fatigue","kind":"term","name":"Cancer-related fatigue (tiredness)","route":"/terms/cancer-related-fatigue/"},{"id":"central-venous-access","kind":"term","name":"Central venous access (port, PICC line)","route":"/terms/central-venous-access/"},{"id":"febrile-neutropenia","kind":"term","name":"Febrile neutropenia","route":"/terms/febrile-neutropenia/"},{"id":"financial-toxicity","kind":"term","name":"Financial toxicity","route":"/terms/financial-toxicity/"},{"id":"hypogammaglobulinaemia","kind":"term","name":"Hypogammaglobulinaemia and infection risk after B-cell therapies","route":"/terms/hypogammaglobulinaemia/"},{"id":"lymphoma-tx-pjp-and-infection-prophylaxis","kind":"term","name":"Infection prophylaxis in lymphoma: PJP, herpes, fungal risk and vaccination","route":"/terms/lymphoma-tx-pjp-and-infection-prophylaxis/"},{"id":"late-effects","kind":"term","name":"Late effects and survivorship toxicity","route":"/terms/late-effects/"},{"id":"lymphoma-living-indolent-lymphoma","kind":"term","name":"Living with an indolent lymphoma rather than being cured of one","route":"/terms/lymphoma-living-indolent-lymphoma/"},{"id":"lymphoma-living-infection-years-after","kind":"term","name":"Low antibodies and infection risk for years after anti-CD20 and bispecific antibodies","route":"/terms/lymphoma-living-infection-years-after/"},{"id":"neutropenia","kind":"term","name":"Neutropenia","route":"/terms/neutropenia/"},{"id":"lymphoma-decision-watch-and-wait","kind":"term","name":"Watch and wait in follicular lymphoma: being told you have cancer and that nobody will treat it","route":"/terms/lymphoma-decision-watch-and-wait/"},{"id":"lymphoma-tx-watch-and-wait","kind":"term","name":"Watch and wait in lymphoma: when the right treatment is none yet","route":"/terms/lymphoma-tx-watch-and-wait/"},{"id":"watchful-waiting","kind":"term","name":"Watchful waiting, and how it differs from active surveillance","route":"/terms/watchful-waiting/"}],"trial":[{"id":"augment","kind":"trial","name":"AUGMENT","route":"/trials/augment/"},{"id":"mosun-len-mzl","kind":"trial","name":"Mosunetuzumab with lenalidomide in relapsed marginal zone lymphoma","route":"/trials/mosun-len-mzl/"}],"paper":[{"id":"paper-magnolia-zanubrutinib-mzl-ccr-2021","kind":"paper","name":"MAGNOLIA: zanubrutinib in relapsed or refractory marginal zone lymphoma","route":"/key-papers/paper-magnolia-zanubrutinib-mzl-ccr-2021/"},{"id":"paper-esmo-marginal-zone-lymphoma-zucca-ann-oncol-2020","kind":"paper","name":"Marginal zone lymphomas: ESMO clinical practice guidelines","route":"/key-papers/paper-esmo-marginal-zone-lymphoma-zucca-ann-oncol-2020/"}],"technology":[{"id":"palliative-care","kind":"technology","name":"Early integrated palliative care","route":"/technologies/palliative-care/"},{"id":"exercise-during-chemotherapy","kind":"technology","name":"Exercise during chemotherapy and radiotherapy","route":"/technologies/exercise-during-chemotherapy/"},{"id":"multidisciplinary-tumour-board","kind":"technology","name":"Multidisciplinary tumour boards","route":"/technologies/multidisciplinary-tumour-board/"},{"id":"fertility-preservation","kind":"technology","name":"Oncofertility and fertility preservation","route":"/technologies/fertility-preservation/"},{"id":"peer-support-groups","kind":"technology","name":"Peer support and support groups","route":"/technologies/peer-support-groups/"},{"id":"prehabilitation","kind":"technology","name":"Prehabilitation before cancer surgery","route":"/technologies/prehabilitation/"},{"id":"psycho-oncology","kind":"technology","name":"Psycho-oncology and distress screening","route":"/technologies/psycho-oncology/"},{"id":"survivorship-care-plan","kind":"technology","name":"Survivorship care and late-effects surveillance","route":"/technologies/survivorship-care-plan/"}]}}