Compendium of Cancer Genome Aberrations

HAEM5:Systemic EBV-positive T-cell lymphoma of childhood: Difference between revisions

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==Primary Author(s)*==
==Primary Author(s)*==
Karin Miller, MD; Cedars-Sinai, Los Angeles, CA


*Karin Miller, MD
==WHO Classification of Disease==
==WHO Classification of Disease==


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|Subtype(s)
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|Systemic EBV-positive T-cell lymphoma of childhood
|Systemic EBV-positive T-cell lymphoma of childhood (SEBVTCL)
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==Gene Rearrangements==
==Gene Rearrangements==
Monoclonal T-cell receptor gene rearrangements in most cases.<ref name=":1">{{Cite journal|last=Quintanilla-Martinez|first=L.|last2=Kumar|first2=S.|last3=Fend|first3=F.|last4=Reyes|first4=E.|last5=Teruya-Feldstein|first5=J.|last6=Kingma|first6=D. W.|last7=Sorbara|first7=L.|last8=Raffeld|first8=M.|last9=Straus|first9=S. E.|date=2000-07-15|title=Fulminant EBV(+) T-cell lymphoproliferative disorder following acute/chronic EBV infection: a distinct clinicopathologic syndrome|url=https://pubmed.ncbi.nlm.nih.gov/10887104|journal=Blood|volume=96|issue=2|pages=443–451|issn=0006-4971|pmid=10887104}}</ref><ref name=":7">{{Cite journal|last=Coffey|first=Amy M.|last2=Lewis|first2=Annisa|last3=Marcogliese|first3=Andrea N.|last4=Elghetany|first4=M. Tarek|last5=Punia|first5=Jyotinder N.|last6=Chang|first6=Chung-Che|last7=Allen|first7=Carl E.|last8=McClain|first8=Kenneth L.|last9=Gaikwad|first9=Amos S.|date=2019-08|title=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|url=https://pubmed.ncbi.nlm.nih.gov/31099136|journal=Pediatric Blood & Cancer|volume=66|issue=8|pages=e27798|doi=10.1002/pbc.27798|issn=1545-5017|pmid=31099136}}</ref> T-cell clonality can also be detected in EBV-associated HLH and other EBV-associated disorders.<ref name=":10">{{Cite journal|last=Dojcinov|first=Stefan D.|last2=Quintanilla-Martinez|first2=Leticia|date=2023-01-04|title=How I Diagnose EBV-Positive B- and T-Cell Lymphoproliferative Disorders|url=https://pubmed.ncbi.nlm.nih.gov/36214507|journal=American Journal of Clinical Pathology|volume=159|issue=1|pages=14–33|doi=10.1093/ajcp/aqac105|issn=1943-7722|pmid=36214507}}</ref>
Monoclonal T-cell receptor gene rearrangements in most cases.<ref name=":1">{{Cite journal|last=Quintanilla-Martinez|first=L.|last2=Kumar|first2=S.|last3=Fend|first3=F.|last4=Reyes|first4=E.|last5=Teruya-Feldstein|first5=J.|last6=Kingma|first6=D. W.|last7=Sorbara|first7=L.|last8=Raffeld|first8=M.|last9=Straus|first9=S. E.|date=2000-07-15|title=Fulminant EBV(+) T-cell lymphoproliferative disorder following acute/chronic EBV infection: a distinct clinicopathologic syndrome|url=https://pubmed.ncbi.nlm.nih.gov/10887104|journal=Blood|volume=96|issue=2|pages=443–451|issn=0006-4971|pmid=10887104}}</ref><ref name=":7">{{Cite journal|last=Coffey|first=Amy M.|last2=Lewis|first2=Annisa|last3=Marcogliese|first3=Andrea N.|last4=Elghetany|first4=M. Tarek|last5=Punia|first5=Jyotinder N.|last6=Chang|first6=Chung-Che|last7=Allen|first7=Carl E.|last8=McClain|first8=Kenneth L.|last9=Gaikwad|first9=Amos S.|date=2019-08|title=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|url=https://pubmed.ncbi.nlm.nih.gov/31099136|journal=Pediatric Blood & Cancer|volume=66|issue=8|pages=e27798|doi=10.1002/pbc.27798|issn=1545-5017|pmid=31099136}}</ref> T-cell clonality can also be detected in EBV-associated HLH and other EBV-associated disorders.<ref name=":10">{{Cite journal|last=Dojcinov|first=Stefan D.|last2=Quintanilla-Martinez|first2=Leticia|date=2023-01-04|title=How I Diagnose EBV-Positive B- and T-Cell Lymphoproliferative Disorders|url=https://pubmed.ncbi.nlm.nih.gov/36214507|journal=American Journal of Clinical Pathology|volume=159|issue=1|pages=14–33|doi=10.1093/ajcp/aqac105|issn=1943-7722|pmid=36214507}}</ref>  
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==Individual Region Genomic Gain/Loss/LOH==
==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.<ref name=":0">Arber DA, Borowitz MJ, Cook JR, et al. ''The International Consensus Classification of Myeloid and Lymphoid Neoplasms''.; 2025.</ref> <ref name=":3" /><ref name=":6" /><ref name=":10" />
* 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).<ref name=":0">Arber DA, Borowitz MJ, Cook JR, et al. ''The International Consensus Classification of Myeloid and Lymphoid Neoplasms''.; 2025.</ref> <ref name=":3" /><ref name=":6" /><ref name=":10" />
* No observable patterns in the cytogenetic/karyotypic abnormalities to-date; cytogenetic abnormalities associated with worse prognosis<ref name=":7" /><ref name=":5">{{Cite journal|last=Hue|first=Susan Swee-Shan|last2=Oon|first2=Ming Liang|last3=Wang|first3=Shi|last4=Tan|first4=Soo-Yong|last5=Ng|first5=Siok-Bian|date=2020-01|title=Epstein-Barr virus-associated T- and NK-cell lymphoproliferative diseases: an update and diagnostic approach|url=https://pubmed.ncbi.nlm.nih.gov/31767131|journal=Pathology|volume=52|issue=1|pages=111–127|doi=10.1016/j.pathol.2019.09.011|issn=1465-3931|pmid=31767131}}</ref><ref name=":9">{{Cite journal|last=Smith|first=Megan C.|last2=Cohen|first2=Daniel N.|last3=Greig|first3=Bruce|last4=Yenamandra|first4=Ashwini|last5=Vnencak-Jones|first5=Cindy|last6=Thompson|first6=Mary Ann|last7=Kim|first7=Annette S.|date=2014|title=The ambiguous boundary between EBV-related hemophagocytic lymphohistiocytosis and systemic EBV-driven T cell lymphoproliferative disorder|url=https://pubmed.ncbi.nlm.nih.gov/25337215|journal=International Journal of Clinical and Experimental Pathology|volume=7|issue=9|pages=5738–5749|issn=1936-2625|pmc=4203186|pmid=25337215}}</ref><ref>{{Cite journal|last=Chen|first=J. S.|last2=Tzeng|first2=C. C.|last3=Tsao|first3=C. J.|last4=Su|first4=W. C.|last5=Chen|first5=T. Y.|last6=Jung|first6=Y. C.|last7=Su|first7=I. J.|date=1997-09|title=Clonal karyotype abnormalities in EBV-associated hemophagocytic syndrome|url=https://pubmed.ncbi.nlm.nih.gov/9407723|journal=Haematologica|volume=82|issue=5|pages=572–576|issn=0390-6078|pmid=9407723}}</ref>
* No observable patterns in the cytogenetic/karyotypic abnormalities to-date; cytogenetic abnormalities associated with worse prognosis<ref name=":7" /><ref name=":5">{{Cite journal|last=Hue|first=Susan Swee-Shan|last2=Oon|first2=Ming Liang|last3=Wang|first3=Shi|last4=Tan|first4=Soo-Yong|last5=Ng|first5=Siok-Bian|date=2020-01|title=Epstein-Barr virus-associated T- and NK-cell lymphoproliferative diseases: an update and diagnostic approach|url=https://pubmed.ncbi.nlm.nih.gov/31767131|journal=Pathology|volume=52|issue=1|pages=111–127|doi=10.1016/j.pathol.2019.09.011|issn=1465-3931|pmid=31767131}}</ref><ref name=":9">{{Cite journal|last=Smith|first=Megan C.|last2=Cohen|first2=Daniel N.|last3=Greig|first3=Bruce|last4=Yenamandra|first4=Ashwini|last5=Vnencak-Jones|first5=Cindy|last6=Thompson|first6=Mary Ann|last7=Kim|first7=Annette S.|date=2014|title=The ambiguous boundary between EBV-related hemophagocytic lymphohistiocytosis and systemic EBV-driven T cell lymphoproliferative disorder|url=https://pubmed.ncbi.nlm.nih.gov/25337215|journal=International Journal of Clinical and Experimental Pathology|volume=7|issue=9|pages=5738–5749|issn=1936-2625|pmc=4203186|pmid=25337215}}</ref><ref>{{Cite journal|last=Chen|first=J. S.|last2=Tzeng|first2=C. C.|last3=Tsao|first3=C. J.|last4=Su|first4=W. C.|last5=Chen|first5=T. Y.|last6=Jung|first6=Y. C.|last7=Su|first7=I. J.|date=1997-09|title=Clonal karyotype abnormalities in EBV-associated hemophagocytic syndrome|url=https://pubmed.ncbi.nlm.nih.gov/9407723|journal=Haematologica|volume=82|issue=5|pages=572–576|issn=0390-6078|pmid=9407723}}</ref>
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<blockquote class="blockedit"><center>
</blockquote>
==Characteristic Chromosomal or Other Global Mutational Patterns==
==Characteristic Chromosomal or Other Global Mutational Patterns==


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== Gene Mutations (SNV/INDELS) ==
== Gene Mutations (SNV/INDEL) ==
 
Somatic mutations have been reported; however, consistent/recurrent mutations are not well-described.<ref name=":10" />
* Somatic mutations have been reported; however, consistent/recurrent mutations are not well-described.<ref name=":10" /><ref>{{Cite journal|last=Saleem|first=Atif|last2=Joshi|first2=Rohan|last3=Lei|first3=Li|last4=Lezama|first4=Lhara|last5=Raghavan|first5=Shyam S.|last6=Neishaboori|first6=Nastaran|last7=Roy|first7=Mohana|last8=Schroers-Martin|first8=Joe|last9=Charville|first9=Gregory W.|date=2020-03-01|title=Novel IRF8 and PD-L1 molecular aberrations in systemic EBV-positive T-cell lymphoma of childhood|url=https://www.sciencedirect.com/science/article/pii/S2214330020300055|journal=Human Pathology: Case Reports|volume=19|pages=200356|doi=10.1016/j.ehpc.2020.200356|issn=2214-3300}}</ref><ref name=":2">{{Cite journal|last=Asmussen|first=Anders|last2=Quintanilla-Martinez|first2=Leticia|last3=Larsen|first3=Martin|last4=Fagerberg|first4=Christina|last5=Bækvad-Hansen|first5=Marie|last6=Juul|first6=Maja Bech|last7=Rewers|first7=Kate|last8=Raaschou-Jensen|first8=Klas|last9=Barnkob|first9=Mike Bogetofte|date=2024-01|title=Severe lympho-depletion, abrogated thymopoiesis and systemic EBV positive T-cell lymphoma of childhood, a case|url=https://pubmed.ncbi.nlm.nih.gov/37871127|journal=Leukemia & Lymphoma|volume=65|issue=1|pages=118–122|doi=10.1080/10428194.2023.2264425|issn=1029-2403|pmid=37871127}}</ref>
* ''FYN'' mutations have been reported in two cases <ref name=":10" /><ref>{{Cite journal|last=Asmussen|first=Anders|last2=Quintanilla-Martinez|first2=Leticia|last3=Larsen|first3=Martin|last4=Fagerberg|first4=Christina|last5=Bækvad-Hansen|first5=Marie|last6=Juul|first6=Maja Bech|last7=Rewers|first7=Kate|last8=Raaschou-Jensen|first8=Klas|last9=Barnkob|first9=Mike Bogetofte|date=2024-01|title=Severe lympho-depletion, abrogated thymopoiesis and systemic EBV positive T-cell lymphoma of childhood, a case|url=https://pubmed.ncbi.nlm.nih.gov/37871127|journal=Leukemia & Lymphoma|volume=65|issue=1|pages=118–122|doi=10.1080/10428194.2023.2264425|issn=1029-2403|pmid=37871127}}</ref>
** ''FYN'' mutations have been reported in two cases <ref name=":10" /><ref name=":2" />
* Mutations in ''KMT2D'', ''MFHAS1'', ''STAT3'', ''EP300'', ''ITPKB'', ''DDX3X'', ''NOTCH1'', ''NOTCH2'', and ''TET2'' (amongst others) have also been reported  
** Mutations in ''KMT2D'', ''MFHAS1'', ''STAT3'', ''EP300'', ''ITPKB'', ''DDX3X'', ''NOTCH1'', ''NOTCH2'', ''TET2'', and ''STAT3'' (amongst others) have also been reported<ref>{{Cite journal|last=Gao|first=Li-Min|last2=Zhao|first2=Sha|last3=Zhang|first3=Wen-Yan|last4=Wang|first4=Mi|last5=Li|first5=Hui-Fang|last6=Lizaso|first6=Anle|last7=Liu|first7=Wei-Ping|date=2019|title=Somatic mutations in KMT2D and TET2 associated with worse prognosis in Epstein-Barr virus-associated T or natural killer-cell lymphoproliferative disorders|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC6783120/|journal=Cancer Biology & Therapy|volume=20|issue=10|pages=1319–1327|doi=10.1080/15384047.2019.1638670|issn=1555-8576|pmc=6783120|pmid=31311407}}</ref>
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== Epigenomic Alterations ==
== Epigenomic Alterations ==
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== Genetic Diagnostic Testing Methods ==
== Genetic Diagnostic Testing Methods ==


* WHO 5th edition ''essential'' diagnostic criteria include:<ref name=":3" /><ref name=":6" />
* PCR or NGS for clonal TCR gene rearrangement: clonality is ''desirable'' diagnostic criteria (WHO HAEM5) <ref name=":3" /><ref name=":6" />
** Acute presentation with fever and systemic symptoms
** May be seen in both SEBVTCL and EBV+ nonfamilial HLH <ref name=":3" /><ref name=":0" />
** Multiorgan infiltration by atypical T-cells
** EBV-positivity
** Exclusion of known immunodeficiency


* WHO 5th edition ''desirable'' diagnostic criteria include:<ref name=":3" /><ref name=":6" />
* Conventional cytogenetics: karyotypic abnormalities favor a diagnosis of SEBVTCL over EBV+ nonfamilial HLH (WHO HAEM5 / International Consensus Classification (ICC)) <ref name=":3" /><ref name=":0" />
** Clonal TCR-gene rearrangement
** Differential Diagnosis with EBV+ nonfamilial HLH is challenging
** Hemophagocytic lymphohistiocytosis (HLH)
** Primary/familial EBV+ HLH can be excluded by family history and genetic analysis<ref name=":10" />
** Hepatosplenomegaly
* Chromosome microarray (CMA): detect cytogenetic abnormalities.
* 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.<ref name=":3" /><ref name=":0" />  
** Primary/familial EBV-positive HLH can be excluded by family history and genetic analysis<ref name=":10" />
* TCR-gene rearrangements can be detected via PCR or NGS methods. Cytogenetic abnormalities can be detected with karyotype and chromosome microarray (CMA).


== Familial Forms ==
== Familial Forms ==
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== Links ==
== Links ==
[[HAEM4:EBV-Positive T-cell and NK-cell Lymphoproliferative Diseases of Childhood]]<center><center>
[[HAEM4:EBV-Positive T-cell and NK-cell Lymphoproliferative Diseases of Childhood]]
 
 
 
 
 


== References ==
== References ==
<center><center>
<references />
<center><center>
<center><references />


<br />
== Notes ==
 
[[Category:HAEM5]]
==Notes==
<nowiki>*</nowiki>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 [[Leadership|''<u>Associate Editor</u>'']] 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.
<nowiki>*</nowiki>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 [[Leadership|''<u>Associate Editor</u>'']] 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
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 {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Systemic_EBV-positive_T-cell_lymphoma_of_childhood</nowiki>.<center>
<nowiki>*</nowiki>''Citation of this Page'': “Systemic EBV-positive T-cell lymphoma of childhood”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Systemic_EBV-positive_T-cell_lymphoma_of_childhood</nowiki>.
<center>
[[Category:HAEM5]]
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:Diseases S]]
[[Category:DISEASE]]
[[Category:DISEASE]]
[[Category:Diseases S]]
[[Category:Diseases S]]
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