Nodal marginal zone lymphoma
Haematolymphoid Tumours (5th ed.)
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Primary Author(s)*
Andrew Ly, DO and Shivani Golem, PhD, FACMG
Cancer Category / Type
Cancer Sub-Classification / Subtype
- Nodal Marginal Zone Lymphoma
Definition / Description of Disease
Nodal marginal zone lymphoma (NMZL) is an uncommon subtype of non-Hodgkin lymphoma. It is a primary nodal B-cell lymphoma with histological features similar to Splenic marginal zone lymphoma and Extranodal marginal zone lymphoma involving lymph nodes, but without evidence of splenic or extranodal disease[1].
Synonyms / Terminology
- Monocytoid B-cell lymphoma
- Parafollicular B-cell lymphoma (no longer in use)
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Epidemiology / Prevalence
- 1.5-1.8% of all lymphoid neoplasms
- Median age ~60 years old
- Both sexes are affected equally
- Cases also occur in children and are separately diagnosed as HAEM5:Paediatric nodal marginal zone lymphoma
- Association with autoimmune diseases
- Association with Hepatitis C virus infection reported in some studies but not all studies
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Clinical Features
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| Signs and Symptoms | EXAMPLE Asymptomatic (incidental finding on complete blood counts)
EXAMPLE B-symptoms (weight loss, fever, night sweats) EXAMPLE Fatigue EXAMPLE Lymphadenopathy (uncommon) |
| Laboratory Findings | EXAMPLE Cytopenias
EXAMPLE Lymphocytosis (low level) |
editv4:Clinical FeaturesThe content below was from the old template. Please incorporate above.
- Asymptomatic, localized or generalized lymphadenopathy
- B symptoms (fever, night sweats, and weight loss)
- Bone marrow involvement
The presence of a primary extranodal marginal zone lymphoma should be ruled out due to the possibility of a nodal dissemination of a MALT lymphoma occurring in patients with a history of Sjogren syndrome and Hashimoto thyroiditis[1].
Sites of Involvement
- Lymph nodes
- Bone marrow
- Peripheral blood
Morphologic Features
- Variable populations of lymphoma cells
- Centrocyte-like and monocytoid B-cells
- Plasma cells
- Scattered transformed B cells
- Lymph nodes show small lymphoma cells surrounding reactive follicles (marginal zone distribution)
- Extension to interfollicular areas and follicular colonization may be present
- Diffuse or partial nodal effacement may be present
- Bone marrow shows lymphoma cells in interstitial, nodular, intertrabecular or paratrabecular distribution
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Immunophenotype
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| Finding | Marker |
|---|---|
| Positive (universal) | EXAMPLE CD1 |
| Positive (subset) | EXAMPLE CD2 |
| Negative (universal) | EXAMPLE CD3 |
| Negative (subset) | EXAMPLE CD4 |
editv4:ImmunophenotypeThe content below was from the old template. Please incorporate above.
Finding Marker Positive (B-cell lineage markers) CD19, CD20, CD22, PAX5, FMC7, CD79a, sIg Positive (most cases) BCL2, MNDA, IRTA1 Variable positivity CD5, CD43, CD23 Negative CD10, Cyclin D1, BCL6, LMO2
Chromosomal Rearrangements (Gene Fusions)
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| Chromosomal Rearrangement | Genes in Fusion (5’ or 3’ Segments) | Pathogenic Derivative | Prevalence | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|---|---|---|
| EXAMPLE t(9;22)(q34;q11.2) | EXAMPLE 3'ABL1 / 5'BCR | EXAMPLE der(22) | EXAMPLE 20% (COSMIC)
EXAMPLE 30% (add reference) |
Yes | No | Yes | EXAMPLE
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). |
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editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).Please incorporate this section into the relevant tables found in:
- Chromosomal Rearrangements (Gene Fusions)
- Individual Region Genomic Gain/Loss/LOH
- Characteristic Chromosomal Patterns
- Gene Mutations (SNV/INDEL)
- None.
Individual Region Genomic Gain / Loss / LOH
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| Chr # | Gain / Loss / Amp / LOH | Minimal Region Genomic Coordinates [Genome Build] | Minimal Region Cytoband | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|---|---|---|
| EXAMPLE
7 |
EXAMPLE Loss | EXAMPLE
chr7:1- 159,335,973 [hg38] |
EXAMPLE
chr7 |
Yes | Yes | No | EXAMPLE
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference). |
| EXAMPLE
8 |
EXAMPLE Gain | EXAMPLE
chr8:1-145,138,636 [hg38] |
EXAMPLE
chr8 |
No | No | No | EXAMPLE
Common recurrent secondary finding for t(8;21) (add reference). |
editv4:Genomic Gain/Loss/LOHThe content below was from the old template. Please incorporate above.
Chromosome Number Gain/Loss/Amp/LOH Region 3 Gain N/A 12 Gain N/A 18 Gain N/A 6 Loss 6q23-24
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Characteristic Chromosomal Patterns
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| Chromosomal Pattern | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|
| EXAMPLE
Co-deletion of 1p and 18q |
Yes | No | No | EXAMPLE:
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). |
editv4:Characteristic Chromosomal Aberrations / PatternsThe content below was from the old template. Please incorporate above.
- Deletions in 7q31
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Gene Mutations (SNV / INDEL)
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| Gene; Genetic Alteration | Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other) | Prevalence (COSMIC / TCGA / Other) | Concomitant Mutations | Mutually Exclusive Mutations | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|---|---|---|---|
| EXAMPLE: TP53; Variable LOF mutations
EXAMPLE: EGFR; Exon 20 mutations EXAMPLE: BRAF; Activating mutations |
EXAMPLE: TSG | EXAMPLE: 20% (COSMIC)
EXAMPLE: 30% (add Reference) |
EXAMPLE: IDH1 R123H | EXAMPLE: EGFR amplification | EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference).
|
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
editv4:Gene Mutations (SNV/INDEL)The content below was from the old template. Please incorporate above.Whole-exome sequencing (WES) study have identified mutations involved in NOTCH, nuclear factor κB (NF-κB), B-cell receptors and toll like receptor pathways . In one study, 16% (4/25) of cases identified a BRAF (V600E) mutation with associated strong IgD expression. In one of the four BRAF positive mutation, two non-hotspot mutations were detected (L597Q and N581I) which was previously found in BRAF V600 wild-type melanoma. In the same study, mutations of KMT2D (7/25, 28%), TET2 (5/25, 20%), and EZH2 (5/25, 20%) were among the more frequent mutated genes. CREBBP, TNFRSF14, FAS, TNFAIP3, KLF2, and CXCR4 mutations were also detected[4]. In another study, which investigated genetic lesions in 35 patients with NMZL, PTPRD mutations were found in 14.3% (5/35) of patients and PTPRD locus deletions were found in 5.7% (2/35) of patients[5]. Mutations were also identified in another study for NFKBIE and ITPR2 mutations involved in the NF-κB pathway and B-cell receptor mediated calcium signal pathway. However, in this study they did not find any PTPRD mutations or BRAF mutations, demonstrating the diverseness of the disease[6]. No BRAF mutations have yet to be identified in other studies on NMZL[4].
Other Mutations
Immunoglobulin genes are clonally rearranged consisting of mutated IGHV3 and IGHV4 family members, particularly IGHV4-34 and cases associated with hepatitis C use IGHV1-69[1].
Epigenomic Alterations
- Not known in this specific subtype.
Genes and Main Pathways Involved
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| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| EXAMPLE: BRAF and MAP2K1; Activating mutations | EXAMPLE: MAPK signaling | EXAMPLE: Increased cell growth and proliferation |
| EXAMPLE: CDKN2A; Inactivating mutations | EXAMPLE: Cell cycle regulation | EXAMPLE: Unregulated cell division |
| EXAMPLE: KMT2C and ARID1A; Inactivating mutations | EXAMPLE: Histone modification, chromatin remodeling | EXAMPLE: Abnormal gene expression program |
editv4:Genes and Main Pathways InvolvedThe content below was from the old template. Please incorporate above.
- NF-κB pathway and B-cell receptor mediated calcium signal pathway.
Genetic Diagnostic Testing Methods
- No diagnostic test is specifically established.
Familial Forms
- Not known in this specific subtype.
Additional Information
None
Links
- HAEM5:Paediatric nodal marginal zone lymphoma
- HAEM5:Splenic marginal zone lymphoma
- Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue
References
(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference.)
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 Campo E, et al., (2017). Nodal marginal zone lymphoma, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p263-264.
- ↑ Arcaini, Luca; et al. (2007-01). "Primary nodal marginal zone B-cell lymphoma: clinical features and prognostic assessment of a rare disease". British Journal of Haematology. 136 (2): 301–304. doi:10.1111/j.1365-2141.2006.06437.x. ISSN 0007-1048. Check date values in:
|date=(help) - ↑ Brand, Michiel van den; et al. (2013-07-01). "Recognizing nodal marginal zone lymphoma: recent advances and pitfalls. A systematic review". Haematologica. 98 (7): 1003–1013. doi:10.3324/haematol.2012.083386. ISSN 1592-8721. PMC 3696602. PMID 23813646.CS1 maint: PMC format (link)
- ↑ 4.0 4.1 4.2 4.3 Pillonel, V.; et al. (2018-11). "High-throughput sequencing of nodal marginal zone lymphomas identifies recurrent BRAF mutations". Leukemia. 32 (11): 2412–2426. doi:10.1038/s41375-018-0082-4. ISSN 0887-6924. PMC 6224405. PMID 29556019. Check date values in:
|date=(help)CS1 maint: PMC format (link) - ↑ Spina, Valeria; et al. (2016-09-08). "The genetics of nodal marginal zone lymphoma". Blood. 128 (10): 1362–1373. doi:10.1182/blood-2016-02-696757. ISSN 0006-4971. PMC 5016706. PMID 27335277.CS1 maint: PMC format (link)
- ↑ Koh, Jiwon; et al. (2020-06-23). "Discovery of Novel Recurrent Mutations and Clinically Meaningful Subgroups in Nodal Marginal Zone Lymphoma". Cancers. 12 (6): 1669. doi:10.3390/cancers12061669. ISSN 2072-6694. PMC PMC7352856 Check
|pmc=value (help). PMID 32585984 Check|pmid=value (help).CS1 maint: PMC format (link)
Notes
*Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.
*The hierarchical tumour classification structure displayed on this page is reproduced from the WHO Classification of Tumours with permission from the copyright holder, ©International Agency for Research on Cancer.
*Citation of this Page: “Nodal marginal zone lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 12/13/2023, https://ccga.io/index.php/HAEM5:Nodal_marginal_zone_lymphoma.