{"entity":{"id":"nodal-marginal-zone-lymphoma","kind":"cancer","name":"Nodal marginal zone lymphoma","aka":["NMZL","Nodal marginal zone B cell lymphoma","Nodal marginal zone B-cell lymphoma","Monocytoid B-cell lymphoma","Paediatric nodal marginal zone lymphoma"],"tldr":"Nodal marginal zone lymphoma is a slow-growing lymphoma of the lymph nodes that looks like the MALT and splenic types under the microscope but has no organ or spleen involvement to explain it. It lacks a diagnostic marker, so it is diagnosed by excluding the other small B-cell lymphomas, and it is treated like follicular lymphoma with rituximab-based therapy.","summary":"WHO-HAEM5 keeps nodal marginal zone lymphoma as the nodal member of the family, distinguished from splenic marginal zone lymphoma by its pattern of dissemination and still lacking distinct markers (Alaggio 2022; Spina 2016). Exome, targeted and transcriptome sequencing of 35 cases found a distinctive pattern of lesions: KMT2D (MLL2) mutated in 34 percent, PTPRD in 20 percent, NOTCH2 in 20 percent and KLF2 in 17 percent, with PTPRD mutations enriched in this lymphoma among mature B-cell tumours and linked to loss of phosphatase activity and increased proliferation (Spina 2016). Gene expression profiling against follicular lymphoma identified enriched interleukin, integrin, CD40, PI3K and NF-kB pathways, high SYK and TACI expression, and higher CHIT1, TGFB1 and TACI than the BCL6, LMO2 and CD10 of follicular lymphoma (Blood 2012). A paediatric type with an indolent course is recognised.\n\nHow it differs from its parent: no infection to eradicate and no spleen to remove; it presents like other indolent nodal lymphomas and its main difficulty is telling it from follicular lymphoma and from nodal spread of an extranodal or splenic marginal zone lymphoma.\n\nHow common: no registry share in the sources read; rare.\n\nTreatment: as for follicular lymphoma of the same stage, following the ESMO marginal zone guideline: involved-site radiotherapy for localised disease, watch and wait or rituximab with or without chemotherapy for advanced disease, and lenalidomide-rituximab or BTK inhibitors on relapse (Zucca 2020).","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Marginal_zone_B-cell_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":"Spina 2016, Blood: the genetics of nodal marginal zone lymphoma","url":"https://doi.org/10.1182/blood-2016-02-696757"},{"label":"Blood 2012: nodal marginal zone lymphoma gene expression and miRNA profiling","url":"https://doi.org/10.1182/blood-2011-02-339556"}],"tags":["subtype-page","wave4","haematologic","rare"],"related":["marginal-zone-lymphoma","malt-lymphoma","splenic-marginal-zone-lymphoma","follicular-lymphoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["rituximab","bendamustine","lenalidomide","zanubrutinib"],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-tx-watch-and-wait","lymphoma-tx-radiotherapy"],"trials":["augment","fort"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"Rare; the largest genetic study holds 35 patients (Spina 2016). The ESMO guideline gives it as the rarest or second rarest of the three marginal zone lymphomas; no registry share is in the sources read.","subtypes":["Nodal marginal zone lymphoma, adult type (KMT2D, PTPRD, NOTCH2 and KLF2 mutations)","Paediatric nodal marginal zone lymphoma (indolent, localised, young males)","Nodal marginal zone lymphoma with plasmacytic differentiation"],"biomarkers":["Exclusion immunophenotype: CD20 positive, CD5, CD10, cyclin D1 and BCL6 negative","KMT2D, PTPRD, NOTCH2 and KLF2 mutations","Absence of extranodal or splenic disease on staging"],"standardOfCare":[{"setting":"All stages","approach":"Treated as follicular lymphoma of the same stage: radiotherapy when localised, rituximab with or without chemotherapy when advanced, lenalidomide-rituximab or BTK inhibitors on relapse.","refs":["follicular-lymphoma","rituximab","bendamustine","lenalidomide","zanubrutinib"]},{"setting":"Nodal marginal zone lymphoma: treated like follicular lymphoma, with the same choices","approach":"Nodal marginal zone lymphoma has no site-specific treatment of its own and is managed on the follicular lymphoma pathway: watch and wait while asymptomatic, involved-site radiotherapy at 24 Gy for genuinely localised disease, and rituximab-based chemoimmunotherapy (bendamustine and rituximab, or R-CVP) when the disease causes symptoms, organ compromise or cytopenias. Lenalidomide with rituximab is supported by AUGMENT, which enrolled marginal zone as well as follicular lymphoma and gave median progression-free survival of 39.4 against 14.1 months for rituximab alone. Zanubrutinib is an option at relapse on the strength of MAGNOLIA. Hepatitis C should be tested for, as in the splenic form. Transformation to diffuse large B-cell lymphoma is treated as aggressive lymphoma.","refs":["rituximab","bendamustine","lenalidomide","zanubrutinib","augment","lymphoma-tx-watch-and-wait","lymphoma-tx-radiotherapy","paper-magnolia-zanubrutinib-mzl-ccr-2021"],"guideline":{"version":"ESMO marginal zone lymphomas; NCCN B-Cell Lymphomas; AUGMENT, MAGNOLIA","url":"https://www.esmo.org/guidelines/esmo-clinical-practice-guidelines-haematological-malignancies"}}],"stateOfArt":[],"history":[],"pipeline":[],"openProblems":[],"parent":"marginal-zone-lymphoma"},"route":"/cancers/nodal-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":"follicular-lymphoma","kind":"cancer","name":"Follicular lymphoma","route":"/cancers/follicular-lymphoma/"},{"id":"marginal-zone-lymphoma","kind":"cancer","name":"Marginal zone lymphoma","route":"/cancers/marginal-zone-lymphoma/"},{"id":"splenic-marginal-zone-lymphoma","kind":"cancer","name":"Splenic marginal zone lymphoma","route":"/cancers/splenic-marginal-zone-lymphoma/"}],"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":"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-tx-radiotherapy","kind":"term","name":"Radiotherapy in lymphoma: involved-site fields, 24 Gy, 4 Gy and total skin electron therapy","route":"/terms/lymphoma-tx-radiotherapy/"},{"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":"fort","kind":"trial","name":"FoRT","route":"/trials/fort/"},{"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/"}],"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/"}]}}