# Nodal marginal zone lymphoma

Source: https://onco.cc/cancers/nodal-marginal-zone-lymphoma/  
OnCo record `nodal-marginal-zone-lymphoma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

How 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.

How common: no registry share in the sources read; rare.

Treatment: 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).

## Fields

- Kind: Cancer
- Last checked: 2026-09-24
- Also known as: NMZL; Nodal marginal zone B cell lymphoma; Nodal marginal zone B-cell lymphoma; Monocytoid B-cell lymphoma; Paediatric nodal marginal zone lymphoma
- Tags: subtype-page; wave4; haematologic; rare
- 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

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/nodal-marginal-zone-lymphoma/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/nodal-marginal-zone-lymphoma/#overview
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/nodal-marginal-zone-lymphoma/#what-it-is [3 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/nodal-marginal-zone-lymphoma/#finding-it [3 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/nodal-marginal-zone-lymphoma/#treating-it [2 settings, 2 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/nodal-marginal-zone-lymphoma/#evidence [3 trials]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/nodal-marginal-zone-lymphoma/#science [4 targets]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/nodal-marginal-zone-lymphoma/where-you-are/ [25 UK centres]
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/nodal-marginal-zone-lymphoma/#living-with-it [11 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/nodal-marginal-zone-lymphoma/coming/ [4 medicines, 1 trial]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/nodal-marginal-zone-lymphoma/data/ [47 connected records]

## Standard of care

- All stages: 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. ([Follicular lymphoma](https://onco.cc/cancers/follicular-lymphoma/), [Rituximab](https://onco.cc/drugs/rituximab/), [Bendamustine](https://onco.cc/drugs/bendamustine/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/), [Zanubrutinib](https://onco.cc/drugs/zanubrutinib/))
- Nodal marginal zone lymphoma: treated like follicular lymphoma, with the same choices: 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. ([Rituximab](https://onco.cc/drugs/rituximab/), [Bendamustine](https://onco.cc/drugs/bendamustine/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/), [Zanubrutinib](https://onco.cc/drugs/zanubrutinib/), [AUGMENT](https://onco.cc/trials/augment/), [Watch and wait in lymphoma: when the right treatment is none yet](https://onco.cc/terms/lymphoma-tx-watch-and-wait/), [Radiotherapy in lymphoma: involved-site fields, 24 Gy, 4 Gy and total skin electron therapy](https://onco.cc/terms/lymphoma-tx-radiotherapy/), [MAGNOLIA: zanubrutinib in relapsed or refractory marginal zone lymphoma](https://onco.cc/key-papers/paper-magnolia-zanubrutinib-mzl-ccr-2021/))

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Marginal_zone_B-cell_lymphoma
- NCI PDQ: adult non-Hodgkin lymphoma treatment: https://www.cancer.gov/types/lymphoma/patient/adult-nhl-treatment-pdq
- Alaggio 2022, Leukemia: the 5th edition WHO classification of haematolymphoid tumours, lymphoid neoplasms: https://doi.org/10.1038/s41375-022-01620-2
- Zucca 2020, Annals of Oncology: marginal zone lymphomas, ESMO clinical practice guidelines: https://doi.org/10.1016/j.annonc.2019.10.010
- Spina 2016, Blood: the genetics of nodal marginal zone lymphoma: https://doi.org/10.1182/blood-2016-02-696757
- Blood 2012: nodal marginal zone lymphoma gene expression and miRNA profiling: https://doi.org/10.1182/blood-2011-02-339556

## Connected records

- cancers: [Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)](https://onco.cc/cancers/malt-lymphoma/), [Follicular lymphoma](https://onco.cc/cancers/follicular-lymphoma/), [Marginal zone lymphoma](https://onco.cc/cancers/marginal-zone-lymphoma/), [Splenic marginal zone lymphoma](https://onco.cc/cancers/splenic-marginal-zone-lymphoma/)
- drugs: [Bendamustine](https://onco.cc/drugs/bendamustine/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/), [Rituximab](https://onco.cc/drugs/rituximab/), [Zanubrutinib](https://onco.cc/drugs/zanubrutinib/)
- terms: [Cancer-related fatigue (tiredness)](https://onco.cc/terms/cancer-related-fatigue/), [Central venous access (port, PICC line)](https://onco.cc/terms/central-venous-access/), [Febrile neutropenia](https://onco.cc/terms/febrile-neutropenia/), [Financial toxicity](https://onco.cc/terms/financial-toxicity/), [Hypogammaglobulinaemia and infection risk after B-cell therapies](https://onco.cc/terms/hypogammaglobulinaemia/), [Late effects and survivorship toxicity](https://onco.cc/terms/late-effects/), [Living with an indolent lymphoma rather than being cured of one](https://onco.cc/terms/lymphoma-living-indolent-lymphoma/), [Low antibodies and infection risk for years after anti-CD20 and bispecific antibodies](https://onco.cc/terms/lymphoma-living-infection-years-after/), [Neutropenia](https://onco.cc/terms/neutropenia/), [Radiotherapy in lymphoma: involved-site fields, 24 Gy, 4 Gy and total skin electron therapy](https://onco.cc/terms/lymphoma-tx-radiotherapy/), [Watch and wait in follicular lymphoma: being told you have cancer and that nobody will treat it](https://onco.cc/terms/lymphoma-decision-watch-and-wait/), [Watch and wait in lymphoma: when the right treatment is none yet](https://onco.cc/terms/lymphoma-tx-watch-and-wait/), [Watchful waiting, and how it differs from active surveillance](https://onco.cc/terms/watchful-waiting/)
- trials: [AUGMENT](https://onco.cc/trials/augment/), [FoRT](https://onco.cc/trials/fort/), [Mosunetuzumab with lenalidomide in relapsed marginal zone lymphoma](https://onco.cc/trials/mosun-len-mzl/)
- key papers: [MAGNOLIA: zanubrutinib in relapsed or refractory marginal zone lymphoma](https://onco.cc/key-papers/paper-magnolia-zanubrutinib-mzl-ccr-2021/)
- technologies: [Early integrated palliative care](https://onco.cc/technologies/palliative-care/), [Exercise during chemotherapy and radiotherapy](https://onco.cc/technologies/exercise-during-chemotherapy/), [Multidisciplinary tumour boards](https://onco.cc/technologies/multidisciplinary-tumour-board/), [Oncofertility and fertility preservation](https://onco.cc/technologies/fertility-preservation/), [Peer support and support groups](https://onco.cc/technologies/peer-support-groups/), [Prehabilitation before cancer surgery](https://onco.cc/technologies/prehabilitation/), [Psycho-oncology and distress screening](https://onco.cc/technologies/psycho-oncology/), [Survivorship care and late-effects surveillance](https://onco.cc/technologies/survivorship-care-plan/)

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JSON: https://onco.cc/api/v1/entities/nodal-marginal-zone-lymphoma.json