Nodal Marginal Zone Lymphoma

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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[1]

  • Monocytoid B-cell lymphoma
  • Parafollicular B-cell lymphoma (no longer in use)

Epidemiology / Prevalence[1][2][3]

  • 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 Paediatric Nodal Marginal Zone Lymphoma
  • Association with autoimmune diseases
  • Association with Hepatitis C virus infection reported in some studies but not all studies

Clinical Features

  • 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[1]

  • Variable populations of lymphoma cells
    1. Centrocyte-like and monocytoid B-cells
    2. Plasma cells
    3. Scattered transformed B cells
  • Lymph nodes show small lymphoma cells surrounding reactive follicles (marginal zone distribution)
    1. Extension to interfollicular areas and follicular colonization may be present
    2. Diffuse or partial nodal effacement may be present
  • Bone marrow shows lymphoma cells in interstitial, nodular, intertrabecular or paratrabecular distribution

Immunophenotype

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)

  • Recurrent chromosomal translocations that are frequent in other lymphoid malignancies and associated with extranodal MZL are not detected[1][4].

Characteristic Chromosomal Aberrations / Patterns[1][4]

  • Deletions in 7q31

Genomic Gain/Loss/LOH[1]

Chromosome Number Gain/Loss/Amp/LOH Region
3 Gain N/A
12 Gain N/A
18 Gain N/A
6 Loss 6q23-24

Gene Mutations (SNV/INDEL)

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].

Epigenomics (Methylation)

  • Not known in this specific subtype.

Genes and Main Pathways Involved

  • NF-κB pathway and B-cell receptor mediated calcium signal pathway.

Diagnostic Testing Methods

  • No diagnostic test is specifically established.

Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

  • None.

Familial Forms

  • Not known in this specific subtype.

Other Information

None

Links

References

  1. 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.
  2. 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)
  3. 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. 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)
  5. 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)
  6. 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.