Systemic EBV-positive T-cell lymphoma of childhood

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Haematolymphoid Tumours (WHO Classification, 5th ed.)

Primary Author(s)*

Karin Miller, MD; Cedars-Sinai, Los Angeles, CA

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 (SEBVTCL)

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 are found in 30-35% of cases of SEBVTCL and their presence favor a diagnosis of SEBVTCL over EBV-positive nonfamilial HLH (WHO 5th edition / International Consensus Classification).[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 N/A N/A N/A N/A 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 N/A N/A N/A N/A N/A

Gene Mutations (SNV/INDEL)

Somatic mutations have been reported; however, consistent/recurrent mutations are not well-described.[3]

  • FYN mutations have been reported in two cases [3][11]
  • Mutations in KMT2D, MFHAS1, STAT3, EP300, ITPKB, DDX3X, NOTCH1, NOTCH2, and TET2 (amongst others) have also been reported
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 N/A N/A N/A N/A N/A N/A

Epigenomic Alterations

N/A

Genes and Main Pathways Involved

N/A

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
N/A N/A N/A

Genetic Diagnostic Testing Methods

  • PCR or NGS for clonal TCR gene rearrangement: clonality is desirable diagnostic criteria (WHO HAEM5) [5][6]
    • May be seen in both SEBVTCL and EBV+ nonfamilial HLH [5][7]
  • Conventional cytogenetics: karyotypic abnormalities favor a diagnosis of SEBVTCL over EBV+ nonfamilial HLH (WHO HAEM5 / International Consensus Classification (ICC)) [5][7]
    • Differential Diagnosis with EBV+ nonfamilial HLH is challenging
    • Primary/familial EBV+ HLH can be excluded by family history and genetic analysis[3]
  • Chromosome microarray (CMA): detect cytogenetic abnormalities.

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[12]
  • Typically occurs following primary acute EBV infection; though, it is rarely reported in patients with a history of systemic chronic active EBV (CAEBV)[3]
  • Harbors type A EBV with the wildtype or 30bp-deleted product of LMP1[1][13][14]

Links

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

References

  1. ↑ 1.0 1.1 1.2 Quintanilla-Martinez, L.; Kumar, S.; Fend, F.; Reyes, E.; Teruya-Feldstein, J.; Kingma, D. W.; Sorbara, L.; Raffeld, M.; Straus, S. E. (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.; Lewis, Annisa; Marcogliese, Andrea N.; Elghetany, M. Tarek; Punia, Jyotinder N.; Chang, Chung-Che; Allen, Carl E.; McClain, Kenneth L.; Gaikwad, Amos S. (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. {{cite journal}}: Check date values in: |date= (help)CS1 maint: article number as page number (link)
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Dojcinov, Stefan D.; Quintanilla-Martinez, Leticia (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.
  4. ↑ van Dongen, J. J. M.; Langerak, A. W.; Brüggemann, M.; Evans, P. a. S.; Hummel, M.; Lavender, F. L.; Delabesse, E.; Davi, F.; Schuuring, E. (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. {{cite journal}}: 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 "BlueBooksOnline". {{cite journal}}: Cite journal requires |journal= (help)
  7. ↑ 7.0 7.1 7.2 Arber DA, Borowitz MJ, Cook JR, et al. The International Consensus Classification of Myeloid and Lymphoid Neoplasms.; 2025.
  8. ↑ Hue, Susan Swee-Shan; Oon, Ming Liang; Wang, Shi; Tan, Soo-Yong; Ng, Siok-Bian (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. {{cite journal}}: Check date values in: |date= (help)
  9. ↑ Smith, Megan C.; Cohen, Daniel N.; Greig, Bruce; Yenamandra, Ashwini; Vnencak-Jones, Cindy; Thompson, Mary Ann; Kim, Annette S. (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.; Tzeng, C. C.; Tsao, C. J.; Su, W. C.; Chen, T. Y.; Jung, Y. C.; Su, I. J. (1997-09). "Clonal karyotype abnormalities in EBV-associated hemophagocytic syndrome". Haematologica. 82 (5): 572–576. ISSN 0390-6078. PMID 9407723. {{cite journal}}: Check date values in: |date= (help)
  11. ↑ Asmussen, Anders; Quintanilla-Martinez, Leticia; Larsen, Martin; Fagerberg, Christina; Bækvad-Hansen, Marie; Juul, Maja Bech; Rewers, Kate; Raaschou-Jensen, Klas; Barnkob, Mike Bogetofte (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. {{cite journal}}: Check date values in: |date= (help)
  12. ↑ Montes-Mojarro, Ivonne A.; Kim, Wook Youn; Fend, Falko; Quintanilla-Martinez, Leticia (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. {{cite journal}}: Check date values in: |date= (help)
  13. ↑ Kasahara, Y.; Yachie, A.; Takei, K.; Kanegane, C.; Okada, K.; Ohta, K.; Seki, H.; Igarashi, N.; Maruhashi, K. (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.
  14. ↑ Suzuki, Keiko; Ohshima, Koichi; Karube, Kennosuke; Suzumiya, Junji; Ohga, Shouichi; Ishihara, Shigehiko; Tamura, Kazuo; Kikuchi, Masahiro (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. {{cite journal}}: Check date values in: |date= (help)

Notes

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Prior Author(s): Lisa A. Lansdon, PhD & Linda D. Cooley, MD, MBA

Citation of this Page: Miller K. “Systemic EBV-positive T-cell lymphoma of childhood”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 04/21/2026, https://ccga.io/index.php/HAEM5:Systemic_EBV-positive_T-cell_lymphoma_of_childhood.

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