Paediatric nodal marginal zone lymphoma

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Haematolymphoid Tumours (5th ed.)

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This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Paediatric Nodal Marginal Zone Lymphoma.

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Primary Author(s)*

  • Kathleen M. Schieffer, PhD
  • Ruthann Pfau, PhD

Cancer Category / Type

Cancer Sub-Classification / Subtype

Definition / Description of Disease

  • Paediatric nodal marginal zone lymphoma (pNMZL) is a rare and distinct entity of NMZL seen in the pediatrics and young adult population[1]
  • pNMZL typically presents with an indolent course and localized disease[1], contrary from classic NMZL seen in adults[2]
  • Typically presents as asymptomatic, localized lymphadenopathy (Stage I)[3][4][5]
  • Laboratory testing: normal serum lactate dehydrogenase (LDH) levels[3][4][5]
  • Prognosis is typically excellent[4][5][6]
    • Five year event free survival: 94±6%[4]
    • Five year overall survival: 100%[4]
  • Complete remission follows surgical resection in most patients with limited/localized disease[4][7]
  • Chemotherapy and radiation therapy have also been used for management of limited stage disease[4][7]

Synonyms / Terminology

  • Monocytoid B-cell lymphoma
  • Parafollicular B-cell lymphoma (obsolete)

Epidemiology / Prevalence

Clinical Features

Put your text here and fill in the table (Instruction: Can include references in the table)

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 Features
The content below was from the old template. Please incorporate above.

Sites of Involvement

Morphologic Features

  • Effacement of lymph node architecture due to expansion of marginal zone and intrafollicular proliferation
    • Expanded marginal zone may be delineated by IgD staining[6][7]
  • Follicular hyperplasia with features of progressive transformation of germinal centers (PTGC)[3][6][7][9]
  • Polymorphic infiltrate composed of small- to medium-sized cells with round nuclei and moderate cytoplasm[3][7]
  • Starry-sky appearance of residual hyperplastic germinal centers[9]

Immunophenotype

  • Similar to adult-type NMZL, pNMZL is almost universally positive for the mature B cell marker CD20 (90-100%) with most cases also expressing the pan-T cell marker CD43 (70-100%)[3][6][7][9][14]
  • A subset of pNMZL express BCL2 (40-50%) and IgD (20-30%)[3][6][7]
  • pNMZL cells are negative for the germinal center markers CD10, BCL6, CD23, and the T cell markers CD3, CD5[3][6][7][10]
  • CD279/PD-1 staining present in reactive germinal centers of pNMZL, compared to positive staining at the periphery of germinal centers in nodal pediatric-type follicular lymphoma[9]
Finding Marker
Positive (universal) CD19, CD20, sIg (bright, monoclonal), CD43
Positive (subset) BCL2, CD279/PD-1, IgD
Negative (universal) CD10, BCL6, CD23, CD5, CD3, LEF1

Chromosomal Rearrangements (Gene Fusions)

Put your text here and fill in the table

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).


editv4:Chromosomal Rearrangements (Gene Fusions)
The content below was from the old template. Please incorporate above.
  • No chromosomal rearrangements or gene fusions associated with pNMZL[8]
  • Clonal rearrangements of immunoglobulin (Ig) region detected in most cases[3][10]


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)
  • No genomic findings currently assist in diagnosis, prognostication, or therapeutic decisions

Individual Region Genomic Gain / Loss / LOH

Put your text here and fill in the table (Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.)

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/LOH
The content below was from the old template. Please incorporate above.
  • Trisomy 3 and 18 are infrequently described chromosomal aberrations reported in pNMZL[10]
    • These chromosome gains have also been described in adult-type NMZL[2][15][16]
Chromosome Number Gain/Loss/Amp/LOH Region Prevalence[3] Reference
3 Gain Whole chromosome 0-20% [10]
18 Gain Whole chromosome 0-5% [10]
13 Gain Whole chromosome 0-5% [14]

Characteristic Chromosomal Patterns

Put your text here (EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis)

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 / Patterns
The content below was from the old template. Please incorporate above.
  • No characteristic chromosomal aberrations or patterns reported

Gene Mutations (SNV / INDEL)

Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.)

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.
  • Genes reported to be altered in adult-type NMZL, including MLL2 (KMT2D), PTPRD, NOTCH2, KLF2, and BRAF,[17][18] have not been described in pNMZL[8]
  • While no recurrent somatic variations have been identified in pNMZL, a somatic variant in AMOTL1 (NM_130847, p.Ala891Thr) was reported in a single individual with pNMZL[8]
Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence Reference
AMOTL1 Missense Oncogene/Tumor Suppressor* Uncertain 1 patient of 4 total (25%) [8]

*The role in cancer is context dependent

Other Mutations

  • Additional studies are needed to assess the spectrum of somatic variation in pNMZL. A single report evaluated the genetic landscape of pNMZL by whole exome sequencing (n=4) identified missense changes in the following genes: AMOTL1, SCAF1, SELPLG, FAM5B, KLHDC4, RAX, PEG3, CHPF, ACTRT3, NRCAM, CHMP1A, CISH, TTC17, NLE1[8]

Epigenomic Alterations

  • None

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Can include references in the table.)

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 Involved
The content below was from the old template. Please incorporate above.
  • AMOTL1 encodes angiomotin like-1 which associates with tight junctions and regulates the Hippo signaling pathway[21][22]

Genetic Diagnostic Testing Methods

  • Histopathology and immunophenotyping
  • Molecular testing (i.e. clonality assessment)

Familial Forms

  • Not described

Additional Information

  • None

Links

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. ↑ 1.0 1.1 Swerdlow SH, Campo E, Harris NL et al (eds) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, Lyon, pp 264-265
  2. ↑ 2.0 2.1 Swerdlow SH, Campo E, Harris NL et al (eds) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, Lyon, pp 263-264
  3. ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 Koo, Matthew; et al. (2017-05). "Pediatric-type Follicular Lymphoma and Pediatric Nodal Marginal Zone Lymphoma: Recent Clinical, Morphologic, Immunophenotypic, and Genetic Insights". Advances in Anatomic Pathology. 24 (3): 128–135. doi:10.1097/PAP.0000000000000144. ISSN 1533-4031. PMID 28277421. Check date values in: |date= (help)
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 Ronceray, Leila; et al. (04 2018). "Children and adolescents with marginal zone lymphoma have an excellent prognosis with limited chemotherapy or a watch-and-wait strategy after complete resection". Pediatric Blood & Cancer. 65 (4). doi:10.1002/pbc.26932. ISSN 1545-5017. PMID 29286565. Check date values in: |date= (help)
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 Makarova, Olga; et al. (09 2018). "Excellent outcome with limited treatment in paediatric patients with marginal zone lymphoma". British Journal of Haematology. 182 (5): 735–739. doi:10.1111/bjh.14868. ISSN 1365-2141. PMID 28771659. Check date values in: |date= (help)
  6. ↑ 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 Quintanilla-Martinez, Leticia; et al. (2016-02). "Indolent lymphomas in the pediatric population: follicular lymphoma, IRF4/MUM1+ lymphoma, nodal marginal zone lymphoma and chronic lymphocytic leukemia". Virchows Archiv: An International Journal of Pathology. 468 (2): 141–157. doi:10.1007/s00428-015-1855-z. ISSN 1432-2307. PMID 26416032. Check date values in: |date= (help)
  7. ↑ 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 7.11 7.12 Taddessee-Heath, Lekidelu. "Marginal zone B-cell lymphoma in children and young adults". Am J Surg Pathol. 24: 522–531. doi:10.1097/00000478-200304000-00014. PMC 6324530. PMID 12657939.CS1 maint: display-authors (link) CS1 maint: PMC format (link)
  8. ↑ 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 Ozawa, Michael G.; et al. (10 2016). "A study of the mutational landscape of pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 29 (10): 1212–1220. doi:10.1038/modpathol.2016.102. ISSN 1530-0285. PMC 5047957. PMID 27338637. Check date values in: |date= (help)
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 9.7 Liu, Qingyan. "Follicular lymphomas in children and young adults: a comparison of the pediatric variant with usual follicular lymphoma". Am J Surg Pathol. 37: 333–343. doi:10.1097/PAS.0b013e31826b9b57. PMID 23108024.CS1 maint: display-authors (link)
  10. ↑ 10.0 10.1 10.2 10.3 10.4 10.5 10.6 10.7 Rizzo, Kathryn. "Marginal zone lymphomas in children and the young adult population; characterization of genetic aberrations by FISH and RT-PCR". Mol Pathol. 23: 866–873. doi:10.1038/modpathol.2010.63. PMC 6329460. PMID 20305621.CS1 maint: display-authors (link) CS1 maint: PMC format (link)
  11. ↑ 11.0 11.1 11.2 11.3 Ganapathi, Karthik A.; et al. (2014-09). "Early lymphoid lesions: conceptual, diagnostic and clinical challenges". Haematologica. 99 (9): 1421–1432. doi:10.3324/haematol.2014.107938. ISSN 1592-8721. PMC 4562530. PMID 25176983. Check date values in: |date= (help)
  12. ↑ Gitelson, Elena; et al. (2010-01). "Pediatric nodal marginal zone lymphoma may develop in the adult population". Leukemia & Lymphoma. 51 (1): 89–94. doi:10.3109/10428190903349670. ISSN 1029-2403. PMC 3572776. PMID 19863176. Check date values in: |date= (help)
  13. ↑ 13.0 13.1 13.2 Attarbaschi, Andishe; et al. (08 2020). "Rare non-Hodgkin lymphoma of childhood and adolescence: A consensus diagnostic and therapeutic approach to pediatric-type follicular lymphoma, marginal zone lymphoma, and nonanaplastic peripheral T-cell lymphoma". Pediatric Blood & Cancer. 67 (8): e28416. doi:10.1002/pbc.28416. ISSN 1545-5017. PMID 32452165 Check |pmid= value (help). Check date values in: |date= (help)
  14. ↑ 14.0 14.1 Elenitoba-Johnson, K. S.; et al. (1997-01). "Marginal zone B-cell lymphoma with monocytoid B-cell lymphocytes in pediatric patients without immunodeficiency. A report of two cases". American Journal of Clinical Pathology. 107 (1): 92–98. doi:10.1093/ajcp/107.1.92. ISSN 0002-9173. PMID 8980374. Check date values in: |date= (help)
  15. ↑ Rinaldi, Andrea; et al. (2011-02-03). "Genome-wide DNA profiling of marginal zone lymphomas identifies subtype-specific lesions with an impact on the clinical outcome". Blood. 117 (5): 1595–1604. doi:10.1182/blood-2010-01-264275. ISSN 1528-0020. PMID 21115979.
  16. ↑ Dierlamm, J.; et al. (1996-01-01). "Marginal zone B-cell lymphomas of different sites share similar cytogenetic and morphologic features". Blood. 87 (1): 299–307. ISSN 0006-4971. PMID 8547655.
  17. ↑ Spina, Valeria; et al. (09 08, 2016). "The genetics of nodal marginal zone lymphoma". Blood. 128 (10): 1362–1373. doi:10.1182/blood-2016-02-696757. ISSN 1528-0020. PMC 5016706. PMID 27335277. Check date values in: |date= (help)
  18. ↑ Pillonel, V.; et al. (11 2018). "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 1476-5551. PMC 6224405. PMID 29556019. Check date values in: |date= (help)
  19. ↑ Parry, Marina; et al. (2013). "Whole exome sequencing identifies novel recurrently mutated genes in patients with splenic marginal zone lymphoma". PloS One. 8 (12): e83244. doi:10.1371/journal.pone.0083244. ISSN 1932-6203. PMC 3862727. PMID 24349473.
  20. ↑ Rossi, Davide; et al. (2012-08-27). "The coding genome of splenic marginal zone lymphoma: activation of NOTCH2 and other pathways regulating marginal zone development". The Journal of Experimental Medicine. 209 (9): 1537–1551. doi:10.1084/jem.20120904. ISSN 1540-9538. PMC 3428941. PMID 22891273.
  21. ↑ Yi, Chunling; et al. (2011-04-12). "A tight junction-associated Merlin-angiomotin complex mediates Merlin's regulation of mitogenic signaling and tumor suppressive functions". Cancer Cell. 19 (4): 527–540. doi:10.1016/j.ccr.2011.02.017. ISSN 1878-3686. PMC 3075552. PMID 21481793.
  22. ↑ Lv, Meng; et al. (2017). "Angiomotin Family Members: Oncogenes or Tumor Suppressors?". International Journal of Biological Sciences. 13 (6): 772–781. doi:10.7150/ijbs.19603. ISSN 1449-2288. PMC 5485632. PMID 28656002.

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. *Citation of this Page: “Paediatric nodal marginal zone lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 12/13/2023, https://ccga.io/index.php/HAEM5:Paediatric_nodal_marginal_zone_lymphoma.

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