Compendium of Cancer Genome Aberrations

Systemic EBV-positive T-cell lymphoma of childhood

Revision as of 21:06, 18 November 2025 by Karin.Miller (talk | contribs) (→Gene Mutations (SNV/INDELS))

Haematolymphoid Tumours (WHO Classification, 5th ed.)

editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification
This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Systemic EBV-Positive T-cell Lymphoma of Childhood.

(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)*

  • Karin Miller, MD

WHO Classification of Disease

Structure Disease
Book Haematolymphoid Tumours (5th ed.)
Category T-cell and NK-cell lymphoid proliferations and lymphomas
Family Mature T-cell and NK-cell neoplasms
Type EBV-positive T-cell and NK-cell lymphoid proliferations and lymphomas of childhood
Subtype(s) Systemic EBV-positive T-cell lymphoma of childhood

Related Terminology

Acceptable N/A
Not Recommended Fulminant EBV-positive T-cell lymphoproliferative disorder of childhood; sporadic fatal infectious mononucleosis; severe chronic active EBV (CAEBV) infection; severe CAEBV with monoclonal EBV-positive T-cell proliferation; fatal EBV-associated haemophagocytic syndrome; fulminant haemophagocytic syndrome

Gene Rearrangements

Monoclonal T-cell receptor gene rearrangements in most cases.[1][2] T-cell clonality can also be detected in EBV-associated HLH and other EBV-associated disorders.[3]

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
T-cell Receptor (TCR) Gene Rearrangements N/A V(D)J rearrangement of T-cell receptor loci[4] N/A Common[1] D Yes The WHO 5th edition notes that diagnosis of SEBVTCL of childhood "may be supported by clonal TR gene rearrangements," and clonal TR gene rearrangements are included as desirable diagnostic criteria.[5][6]

Individual Region Genomic Gain/Loss/LOH

  • Cytogenetic abnormalities found in 30-35% of cases of SEBVTCL of childhood. The WHO 5th edition and International Consensus Classification note that cytogenetic abnormalities favor a diagnosis of SEBVTCL over EBV-positive nonfamilial HLH.[7] [5][6][3]
  • No observable patterns in the cytogenetic/karyotypic abnormalities to-date; cytogenetic abnormalities associated with worse prognosis[2][8][9][10]
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
N/A

Characteristic Chromosomal or Other Global Mutational Patterns

N/A

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
N/A

Gene Mutations (SNV/INDELS)

  • Somatic mutations have been reported; however, consistent/recurrent mutations are not well-described.[3][11][12]
    • FYN mutations have been reported in two cases [3][12]
    • Mutations in KMT2D, MFHAS1, STAT3, EP300, ITPKB, DDX3X, NOTCH1, NOTCH2, TET2, and STAT3 (amongst others) have also been reported[13]
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
N/A

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.

Epigenomic Alterations

N/A

Genes and Main Pathways Involved

N/A

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
N/A

Genetic Diagnostic Testing Methods

  • WHO 5th edition essential diagnostic criteria include:[5][6]
    • Acute presentation with fever and systemic symptoms
    • Multiorgan infiltration by atypical T-cells
    • EBV-positivity
    • Exclusion of known immunodeficiency
  • WHO 5th edition desirable diagnostic criteria include:[5][6]
    • Clonal TCR-gene rearrangement
    • Hemophagocytic lymphohistiocytosis (HLH)
    • Hepatosplenomegaly
  • Differential Diagnosis with EBV-positive HLH is challenging
    • TCR-gene rearrangements and aberrant T-cell phenotypes can be seen in both SEBVTCL of childhood and EBV-positive HLH
    • The WHO 5th edition and International Consensus Classification note that cytogenetic abnormalities favor a diagnosis of SEBVTCL over EBV-positive nonfamilial HLH.[5][7]
    • Primary/familial EBV-positive HLH can be excluded by family history and genetic analysis[3]
  • TCR-gene rearrangements can be detected via PCR or NGS methods. Cytogenetic abnormalities can be detected with karyotype and chromosome microarray (CMA).

Familial Forms

N/A

Additional Information

  • SEBVTCL of childhood shows an increased prevalence in populations from Asia and Latin America, suggesting a potential genetic etiology. However, no specific genetic abnormalities have been detected[14]
  • Typically occurs following primary acute EBV infection; though, it is rarely reported in patients with a history of systemic chronic active EBV (CAEBV)[3]
  • All cases analyzed carry type A EBV with the wildtype or 30 bp deleted product of LMP1[1][15][16]

Links

HAEM4:EBV-Positive T-cell and NK-cell Lymphoproliferative Diseases of Childhood



References

  1. ↑ 1.0 1.1 1.2 Quintanilla-Martinez, L.; et al. (2000-07-15). "Fulminant EBV(+) T-cell lymphoproliferative disorder following acute/chronic EBV infection: a distinct clinicopathologic syndrome". Blood. 96 (2): 443–451. ISSN 0006-4971. PMID 10887104.
  2. ↑ 2.0 2.1 Coffey, Amy M.; et al. (2019-08). "A clinicopathologic study of the spectrum of systemic forms of EBV-associated T-cell lymphoproliferative disorders of childhood: A single tertiary care pediatric institution experience in North America". Pediatric Blood & Cancer. 66 (8): e27798. doi:10.1002/pbc.27798. ISSN 1545-5017. PMID 31099136. Check date values in: |date= (help)
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Dojcinov, Stefan D.; et al. (2023-01-04). "How I Diagnose EBV-Positive B- and T-Cell Lymphoproliferative Disorders". American Journal of Clinical Pathology. 159 (1): 14–33. doi:10.1093/ajcp/aqac105. ISSN 1943-7722. PMID 36214507 Check |pmid= value (help).
  4. ↑ van Dongen, J. J. M.; et al. (2003-12). "Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936". Leukemia. 17 (12): 2257–2317. doi:10.1038/sj.leu.2403202. ISSN 0887-6924. PMID 14671650. Check date values in: |date= (help)
  5. ↑ 5.0 5.1 5.2 5.3 5.4 The WHO Classification of Tumours Editorial Board, ed. Haematolymphoid Tumours: Who Classification of Tumours. 5th ed. International Agency for Research on Cancer; 2024.
  6. ↑ 6.0 6.1 6.2 6.3 "BlueBooksOnline".
  7. ↑ 7.0 7.1 Arber DA, Borowitz MJ, Cook JR, et al. The International Consensus Classification of Myeloid and Lymphoid Neoplasms.; 2025.
  8. ↑ Hue, Susan Swee-Shan; et al. (2020-01). "Epstein-Barr virus-associated T- and NK-cell lymphoproliferative diseases: an update and diagnostic approach". Pathology. 52 (1): 111–127. doi:10.1016/j.pathol.2019.09.011. ISSN 1465-3931. PMID 31767131. Check date values in: |date= (help)
  9. ↑ Smith, Megan C.; et al. (2014). "The ambiguous boundary between EBV-related hemophagocytic lymphohistiocytosis and systemic EBV-driven T cell lymphoproliferative disorder". International Journal of Clinical and Experimental Pathology. 7 (9): 5738–5749. ISSN 1936-2625. PMC 4203186. PMID 25337215.
  10. ↑ Chen, J. S.; et al. (1997-09). "Clonal karyotype abnormalities in EBV-associated hemophagocytic syndrome". Haematologica. 82 (5): 572–576. ISSN 0390-6078. PMID 9407723. Check date values in: |date= (help)
  11. ↑ Saleem, Atif; et al. (2020-03-01). "Novel IRF8 and PD-L1 molecular aberrations in systemic EBV-positive T-cell lymphoma of childhood". Human Pathology: Case Reports. 19: 200356. doi:10.1016/j.ehpc.2020.200356. ISSN 2214-3300.
  12. ↑ 12.0 12.1 Asmussen, Anders; et al. (2024-01). "Severe lympho-depletion, abrogated thymopoiesis and systemic EBV positive T-cell lymphoma of childhood, a case". Leukemia & Lymphoma. 65 (1): 118–122. doi:10.1080/10428194.2023.2264425. ISSN 1029-2403. PMID 37871127 Check |pmid= value (help). Check date values in: |date= (help)
  13. ↑ Gao, Li-Min; et al. (2019). "Somatic mutations in KMT2D and TET2 associated with worse prognosis in Epstein-Barr virus-associated T or natural killer-cell lymphoproliferative disorders". Cancer Biology & Therapy. 20 (10): 1319–1327. doi:10.1080/15384047.2019.1638670. ISSN 1555-8576. PMC 6783120. PMID 31311407.
  14. ↑ Montes-Mojarro, Ivonne A.; et al. (2020-01). "Epstein - Barr virus positive T and NK-cell lymphoproliferations: Morphological features and differential diagnosis". Seminars in Diagnostic Pathology. 37 (1): 32–46. doi:10.1053/j.semdp.2019.12.004. ISSN 0740-2570. PMID 31889602. Check date values in: |date= (help)
  15. ↑ Kasahara, Y.; et al. (2001-09-15). "Differential cellular targets of Epstein-Barr virus (EBV) infection between acute EBV-associated hemophagocytic lymphohistiocytosis and chronic active EBV infection". Blood. 98 (6): 1882–1888. doi:10.1182/blood.v98.6.1882. ISSN 0006-4971. PMID 11535525.
  16. ↑ Suzuki, Keiko; et al. (2004-05). "Clinicopathological states of Epstein-Barr virus-associated T/NK-cell lymphoproliferative disorders (severe chronic active EBV infection) of children and young adults". International Journal of Oncology. 24 (5): 1165–1174. ISSN 1019-6439. PMID 15067338. Check date values in: |date= (help)


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): Lisa A. Lansdon, PhD & Linda D. Cooley, MD, MBA


*Citation of this Page: “Systemic EBV-positive T-cell lymphoma of childhood”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 11/18/2025, https://ccga.io/index.php/HAEM5:Systemic_EBV-positive_T-cell_lymphoma_of_childhood.

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