Paediatric nodal marginal zone lymphoma
Haematolymphoid Tumours (WHO Classification, 5th ed.)
 | This page is under construction |
editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition ClassificationThis page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Paediatric Nodal Marginal Zone Lymphoma.
(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support.)
Primary Author(s)*
- Kathleen M. Schieffer, PhD
- Ruthann Pfau, PhD
WHO Classification of Disease
| Structure | Disease |
|---|---|
| Book | Haematolymphoid Tumours (5th ed.) |
| Category | B-cell lymphoid proliferations and lymphomas |
| Family | Mature B-cell neoplasms |
| Type | Marginal zone lymphoma |
| Subtype(s) | Paediatric nodal marginal zone lymphoma |
WHO Essential and Desirable Genetic Diagnostic Criteria
(Instructions: The table will have the diagnostic criteria from the WHO book autocompleted; remove any non-genetics related criteria. If applicable, add text about other classification systems that define this entity and specify how the genetics-related criteria differ.)
| WHO Essential Criteria (Genetics)* | |
| WHO Desirable Criteria (Genetics)* | |
| Other Classification |
*Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the WHO Classification of Tumours.
Related Terminology
(Instructions: The table will have the related terminology from the WHO autocompleted.)
| Acceptable | |
| Not Recommended |
Gene Rearrangements
Put your text here and fill in the table (Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.)
| Driver Gene | Fusion(s) and Common Partner Genes | Molecular Pathogenesis | Typical Chromosomal Alteration(s) | Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease) | Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|---|
| EXAMPLE: ABL1 | EXAMPLE: BCR::ABL1 | EXAMPLE: The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1. | EXAMPLE: t(9;22)(q34;q11.2) | EXAMPLE: Common (CML) | EXAMPLE: D, P, T | EXAMPLE: Yes (WHO, NCCN) | 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). BCR::ABL1 is generally favorable in CML (add reference). |
| EXAMPLE: CIC | EXAMPLE: CIC::DUX4 | EXAMPLE: Typically, the last exon of CIC is fused to DUX4. The fusion breakpoint in CIC is usually intra-exonic and removes an inhibitory sequence, upregulating PEA3 genes downstream of CIC including ETV1, ETV4, and ETV5. | EXAMPLE: t(4;19)(q25;q13) | EXAMPLE: Common (CIC-rearranged sarcoma) | EXAMPLE: D | EXAMPLE:
DUX4 has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references). | |
| EXAMPLE: ALK | EXAMPLE: ELM4::ALK
|
EXAMPLE: Fusions result in constitutive activation of the ALK tyrosine kinase. The most common ALK fusion is EML4::ALK, with breakpoints in intron 19 of ALK. At the transcript level, a variable (5’) partner gene is fused to 3’ ALK at exon 20. Rarely, ALK fusions contain exon 19 due to breakpoints in intron 18. | EXAMPLE: N/A | EXAMPLE: Rare (Lung adenocarcinoma) | EXAMPLE: T | EXAMPLE:
Both balanced and unbalanced forms are observed by FISH (add references). | |
| EXAMPLE: ABL1 | EXAMPLE: N/A | EXAMPLE: Intragenic deletion of exons 2–7 in EGFR removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways. | EXAMPLE: N/A | EXAMPLE: Recurrent (IDH-wildtype Glioblastoma) | EXAMPLE: D, P, T | ||
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[1]
- Clonal rearrangements of immunoglobulin (Ig) region detected in most cases[2][3]
End of V4 Section
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
End of V4 Section
Individual Region Genomic Gain/Loss/LOH
Put your text here and fill in the table (Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.)
| Chr # | Gain, Loss, Amp, LOH | Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size] | Relevant Gene(s) | Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|
| EXAMPLE:
7 |
EXAMPLE: Loss | EXAMPLE:
chr7 |
EXAMPLE:
Unknown |
EXAMPLE: D, P | EXAMPLE: 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 references). |
| EXAMPLE:
8 |
EXAMPLE: Gain | EXAMPLE:
chr8 |
EXAMPLE:
Unknown |
EXAMPLE: D, P | EXAMPLE:
Common recurrent secondary finding for t(8;21) (add references). | |
| EXAMPLE:
17 |
EXAMPLE: Amp | EXAMPLE:
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb] |
EXAMPLE:
ERBB2 |
EXAMPLE: D, P, T | EXAMPLE:
Amplification of ERBB2 is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined. | |
editv4:Genomic Gain/Loss/LOHThe content below was from the old template. Please incorporate above.
- Trisomy 3 and 18 are infrequently described chromosomal aberrations reported in pNMZL[3]
| Chromosome Number | Gain/Loss/Amp/LOH | Region | Prevalence[2] | Reference |
|---|---|---|---|---|
| 3 | Gain | Whole chromosome | 0-20% | [3] |
| 18 | Gain | Whole chromosome | 0-5% | [3] |
| 13 | Gain | Whole chromosome | 0-5% | [7] |
End of V4 Section
Characteristic Chromosomal or Other Global Mutational Patterns
Put your text here and fill in the table (Instructions: Included in this category are alterations such as 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; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.)
| Chromosomal Pattern | Molecular Pathogenesis | Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease) |
Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|
| EXAMPLE:
Co-deletion of 1p and 18q |
EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). | EXAMPLE: Common (Oligodendroglioma) | EXAMPLE: D, P | ||
| EXAMPLE:
Microsatellite instability - hypermutated |
EXAMPLE: Common (Endometrial carcinoma) | EXAMPLE: P, T | |||
editv4:Characteristic Chromosomal Aberrations / PatternsThe content below was from the old template. Please incorporate above.
- No characteristic chromosomal aberrations or patterns reported
End of V4 Section
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 or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries 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. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.)
| Gene | Genetic Alteration | Tumor Suppressor Gene, Oncogene, Other | Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease) |
Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|
| EXAMPLE:EGFR
|
EXAMPLE: Exon 18-21 activating mutations | EXAMPLE: Oncogene | EXAMPLE: Common (lung cancer) | EXAMPLE: T | EXAMPLE: Yes (NCCN) | EXAMPLE: Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references). |
| EXAMPLE: TP53; Variable LOF mutations
|
EXAMPLE: Variable LOF mutations | EXAMPLE: Tumor Supressor Gene | EXAMPLE: Common (breast cancer) | EXAMPLE: P | EXAMPLE: >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer. | |
| EXAMPLE: BRAF; Activating mutations | EXAMPLE: Activating mutations | EXAMPLE: Oncogene | EXAMPLE: Common (melanoma) | EXAMPLE: T | ||
Note: A more extensive list of mutations can be found in cBioportal, COSMIC, 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,[8][9] have not been described in pNMZL[1]
- 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[1]
- Missense alterations in AMOTL1 have been reported in adult splenic marginal zone lymphoma (p.Ala424Thr and p.Val361Ile)[10][11] and other cancers (COSMIC, cBioPortal, PedcBioPortal)
| 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%) | [1] |
*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[1]
End of V4 Section
Epigenomic Alterations
- None
Genes and Main Pathways Involved
Put your text here and fill in the table (Instructions: Please include references throughout the table. Do not delete 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 InvolvedThe 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[12][13]
End of V4 Section
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 where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. 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. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted.)
- ↑ 1.0 1.1 1.2 1.3 1.4 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) - ↑ 2.0 2.1 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) - ↑ 3.0 3.1 3.2 3.3 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)
- ↑ Swerdlow SH, Campo E, Harris NL et al (eds) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, Lyon, pp 263-264
- ↑ 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.
- ↑ 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.
- ↑ 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) - ↑ 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) - ↑ 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) - ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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 Associate Editor or other CCGA representative. When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
Prior Author(s):
*Citation of this Page: “Paediatric nodal marginal zone lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 02/11/2025, https://ccga.io/index.php/HAEM5:Paediatric_nodal_marginal_zone_lymphoma.