Paediatric Nodal Marginal Zone Lymphoma

From Compendium of Cancer Genome Aberrations
Jump to navigation Jump to search

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

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]


  • 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)

  • No chromosomal rearrangements or gene fusions associated with pNMZL[8]
  • Clonal rearrangements of immunoglobulin (Ig) region detected in most cases[3][10]

Characteristic Chromosomal Aberrations / Patterns

  • No characteristic chromosomal aberrations or patterns reported

Genomic Gain/Loss/LOH

  • 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]

Gene Mutations (SNV/INDEL)

  • 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]

Epigenomics (Methylation)

  • None

Genes and Main Pathways Involved

  • AMOTL1 encodes angiomotin like-1 which associates with tight junctions and regulates the Hippo signaling pathway[21][22]

Diagnostic Testing Methods

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

Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

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

Familial Forms

  • Not described

Other Information

  • None



  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.


*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.