Compendium of Cancer Genome Aberrations

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

← Older edit
VisualWikitext
No edit summary
Section title fix
 
(8 intermediate revisions by 2 users not shown)
Line 1: Line 1:
{{DISPLAYTITLE:Systemic EBV-positive T-cell lymphoma of childhood}}
{{DISPLAYTITLE:Systemic EBV-positive T-cell lymphoma of childhood}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
{{Under Construction}}
<blockquote class="blockedit">{{Box-round|title=Content 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]].
}}</blockquote>
<span style="color:#0070C0">(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 [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], 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 </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)</span>


==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==


Line 31: Line 24:
|-
|-
|Subtype(s)
|Subtype(s)
|Systemic EBV-positive T-cell lymphoma of childhood
|Systemic EBV-positive T-cell lymphoma of childhood (SEBVTCL)
|}
|}


Line 37: Line 30:


{| class="wikitable"
{| class="wikitable"
|+
|Acceptable
|Acceptable
|N/A
|N/A
Line 46: Line 38:


==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>  
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
Line 66: Line 58:
==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>
{| class="wikitable sortable"
{| class="wikitable sortable"
Line 76: Line 68:
|-
|-
|N/A
|N/A
|
|N/A
|
|N/A
|
|N/A
|
|N/A
|
|N/A
|
|
|}
|}
<blockquote class="blockedit"><center>
</blockquote>
==Characteristic Chromosomal or Other Global Mutational Patterns==
==Characteristic Chromosomal or Other Global Mutational Patterns==


Line 100: Line 89:
|-
|-
|N/A
|N/A
|
|N/A
|
|N/A
|
|N/A
|
|N/A
|
|N/A
|}
|}


== 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>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
Line 121: Line 109:
|-
|-
|N/A
|N/A
|
|N/A
|
|N/A
|
|N/A
|
|N/A
|
|N/A
|
|N/A
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
|}
 
== Epigenomic Alterations ==
== Epigenomic Alterations ==
N/A
N/A
Line 139: Line 126:
|-
|-
|N/A
|N/A
|
|N/A
|
|N/A
|}
|}


== 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 ==
Line 172: Line 151:


== 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]]
Retrieved from "https://content.ccga.io/index.php/HAEM5:Systemic_EBV-positive_T-cell_lymphoma_of_childhood"