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

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)

  • 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

Links

References

  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

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