HAEM5:Systemic EBV-positive T-cell lymphoma of childhood - Revision history

Karin.Miller: /* Gene Rearrangements */

2025-11-20T17:46:02Z

Gene Rearrangements

← Older revision		Revision as of 12:46, 20 November 2025
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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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Karin.Miller: /* Gene Mutations (SNV/INDELS) */

2025-11-19T22:49:05Z

Gene Mutations (SNV/INDELS)

← Older revision		Revision as of 17:49, 19 November 2025
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	* 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>		* 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 name=":2" />		** ''FYN'' mutations have been reported in two cases <ref name=":10" /><ref name=":2" />
	** 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>		** Mutations in ''KMT2D'', ''MFHAS1'', ''STAT3'', ''EP300'', ''ITPKB'', ''DDX3X'', ''NOTCH1'', ''NOTCH2'', and ''TET2'' (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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	== Genetic Diagnostic Testing Methods ==		== Genetic Diagnostic Testing Methods ==

	* WHO 5th edition ''~~essential~~'' diagnostic criteria ~~include:~~<ref name=":3" /><ref name=":6" />		* In the WHO 5th edition, clonal TCR-gene rearrangements are included as ''desirable'' diagnostic criteria for the diagnosis of SEBVTCL of childhood<ref name=":3" /><ref name=":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:<ref name=":3" /><ref name=":6" />
	** Clonal TCR-gene rearrangement
	** Hemophagocytic lymphohistiocytosis (HLH)
	** Hepatosplenomegaly
	* Differential Diagnosis with EBV-positive HLH is challenging		* 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		** TCR-gene rearrangements and aberrant T-cell phenotypes can be seen in both SEBVTCL of childhood and EBV-positive HLH

Karin.Miller: /* Primary Author(s)* */

2025-11-19T02:10:09Z

Primary Author(s)*

← Older revision		Revision as of 21:10, 18 November 2025
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	{{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 at 02:09, 19 November 2025

2025-11-19T02:09:08Z

← Older revision		Revision as of 21:09, 18 November 2025
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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]]<center><center>




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

Karin.Miller: /* Additional Information */

2025-11-19T02:08:50Z

Additional Information

← Older revision		Revision as of 21:08, 18 November 2025
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	* 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<ref>{{Cite journal\|last=Montes-Mojarro\|first=Ivonne A.\|last2=Kim\|first2=Wook Youn\|last3=Fend\|first3=Falko\|last4=Quintanilla-Martinez\|first4=Leticia\|date=2020-01\|title=Epstein - Barr virus positive T and NK-cell lymphoproliferations: Morphological features and differential diagnosis\|url=https://pubmed.ncbi.nlm.nih.gov/31889602\|journal=Seminars in Diagnostic Pathology\|volume=37\|issue=1\|pages=32–46\|doi=10.1053/j.semdp.2019.12.004\|issn=0740-2570\|pmid=31889602}}</ref>		* 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<ref>{{Cite journal\|last=Montes-Mojarro\|first=Ivonne A.\|last2=Kim\|first2=Wook Youn\|last3=Fend\|first3=Falko\|last4=Quintanilla-Martinez\|first4=Leticia\|date=2020-01\|title=Epstein - Barr virus positive T and NK-cell lymphoproliferations: Morphological features and differential diagnosis\|url=https://pubmed.ncbi.nlm.nih.gov/31889602\|journal=Seminars in Diagnostic Pathology\|volume=37\|issue=1\|pages=32–46\|doi=10.1053/j.semdp.2019.12.004\|issn=0740-2570\|pmid=31889602}}</ref>
	* Typically occurs following primary acute EBV infection; though, it is rarely reported in patients with a history of systemic chronic active EBV (CAEBV)<ref name=":10" />		* Typically occurs following primary acute EBV infection; though, it is rarely reported in patients with a history of systemic chronic active EBV (CAEBV)<ref name=":10" />
	* ~~All cases analyzed carry~~ type A EBV with the wildtype or ~~30 bp~~ deleted product of ''LMP1''<ref name=":1" /><ref name=":8">{{Cite journal\|last=Kasahara\|first=Y.\|last2=Yachie\|first2=A.\|last3=Takei\|first3=K.\|last4=Kanegane\|first4=C.\|last5=Okada\|first5=K.\|last6=Ohta\|first6=K.\|last7=Seki\|first7=H.\|last8=Igarashi\|first8=N.\|last9=Maruhashi\|first9=K.\|date=2001-09-15\|title=Differential cellular targets of Epstein-Barr virus (EBV) infection between acute EBV-associated hemophagocytic lymphohistiocytosis and chronic active EBV infection\|url=https://pubmed.ncbi.nlm.nih.gov/11535525\|journal=Blood\|volume=98\|issue=6\|pages=1882–1888\|doi=10.1182/blood.v98.6.1882\|issn=0006-4971\|pmid=11535525}}</ref><ref>{{Cite journal\|last=Suzuki\|first=Keiko\|last2=Ohshima\|first2=Koichi\|last3=Karube\|first3=Kennosuke\|last4=Suzumiya\|first4=Junji\|last5=Ohga\|first5=Shouichi\|last6=Ishihara\|first6=Shigehiko\|last7=Tamura\|first7=Kazuo\|last8=Kikuchi\|first8=Masahiro\|date=2004-05\|title=Clinicopathological states of Epstein-Barr virus-associated T/NK-cell lymphoproliferative disorders (severe chronic active EBV infection) of children and young adults\|url=https://pubmed.ncbi.nlm.nih.gov/15067338\|journal=International Journal of Oncology\|volume=24\|issue=5\|pages=1165–1174\|issn=1019-6439\|pmid=15067338}}</ref>		* Harbors type A EBV with the wildtype or 30bp-deleted product of ''LMP1''<ref name=":1" /><ref name=":8">{{Cite journal\|last=Kasahara\|first=Y.\|last2=Yachie\|first2=A.\|last3=Takei\|first3=K.\|last4=Kanegane\|first4=C.\|last5=Okada\|first5=K.\|last6=Ohta\|first6=K.\|last7=Seki\|first7=H.\|last8=Igarashi\|first8=N.\|last9=Maruhashi\|first9=K.\|date=2001-09-15\|title=Differential cellular targets of Epstein-Barr virus (EBV) infection between acute EBV-associated hemophagocytic lymphohistiocytosis and chronic active EBV infection\|url=https://pubmed.ncbi.nlm.nih.gov/11535525\|journal=Blood\|volume=98\|issue=6\|pages=1882–1888\|doi=10.1182/blood.v98.6.1882\|issn=0006-4971\|pmid=11535525}}</ref><ref>{{Cite journal\|last=Suzuki\|first=Keiko\|last2=Ohshima\|first2=Koichi\|last3=Karube\|first3=Kennosuke\|last4=Suzumiya\|first4=Junji\|last5=Ohga\|first5=Shouichi\|last6=Ishihara\|first6=Shigehiko\|last7=Tamura\|first7=Kazuo\|last8=Kikuchi\|first8=Masahiro\|date=2004-05\|title=Clinicopathological states of Epstein-Barr virus-associated T/NK-cell lymphoproliferative disorders (severe chronic active EBV infection) of children and young adults\|url=https://pubmed.ncbi.nlm.nih.gov/15067338\|journal=International Journal of Oncology\|volume=24\|issue=5\|pages=1165–1174\|issn=1019-6439\|pmid=15067338}}</ref>

	== Links ==		== Links ==

Karin.Miller: /* Gene Mutations (SNV/INDELS) */

2025-11-19T02:06:11Z

Gene Mutations (SNV/INDELS)

← Older revision		Revision as of 21:06, 18 November 2025
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	* 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>		* 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 name=":2" />		** ''FYN'' mutations have been reported in two cases <ref name=":10" /><ref name=":2" />
	** Mutations in KMT2D, MFHAS1, STAT3, EP300, ITPKB, DDX3X, NOTCH1, NOTCH2, TET2~~, DDX3X~~, 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>		** 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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Karin.Miller: /* Gene Mutations (SNV/INDELS) */

2025-11-19T02:01:29Z

Gene Mutations (SNV/INDELS)

← Older revision		Revision as of 21:01, 18 November 2025
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	* 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>		* 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 name=":2" />		** FYN mutations have been reported in two cases <ref name=":10" /><ref name=":2" />
			** Mutations in KMT2D, MFHAS1, STAT3, EP300, ITPKB, DDX3X, NOTCH1, NOTCH2, TET2, DDX3X, 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"
	\|-		\|-

Karin.Miller: /* Genetic Diagnostic Testing Methods */

2025-11-19T01:49:59Z

Genetic Diagnostic Testing Methods

← Older revision		Revision as of 20:49, 18 November 2025
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	** Acute presentation with fever and systemic symptoms		** Acute presentation with fever and systemic symptoms
	** Multiorgan infiltration by atypical T-cells		** Multiorgan infiltration by atypical T-cells
	** EBV-positivity ~~exclusion~~ of known immunodeficiency		** EBV-positivity
			** Exclusion of known immunodeficiency

	* WHO 5th edition ''desirable'' diagnostic criteria include:<ref name=":3" /><ref name=":6" />		* WHO 5th edition ''desirable'' diagnostic criteria include:<ref name=":3" /><ref name=":6" />

Karin.Miller: /* Genetic Diagnostic Testing Methods */

2025-11-19T01:47:28Z

Genetic Diagnostic Testing Methods

← Older revision		Revision as of 20:47, 18 November 2025
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	** 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" />		** 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" />		** 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~~/or~~ chromosome microarray (CMA).		* 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 ==

Karin.Miller: /* Genetic Diagnostic Testing Methods */

2025-11-19T01:47:10Z

Genetic Diagnostic Testing Methods

← Older revision		Revision as of 20:47, 18 November 2025
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	** 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" />		** 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" />		** 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. ~~Of note, T-cell clonality can also be detected in EBV-associated HLH and other EBV-associated disorders.<ref name=":10" />~~ Cytogenetic abnormalities can be detected with karyotype and/or chromosome microarray (CMA).		* TCR-gene rearrangements can be detected via PCR or NGS methods. Cytogenetic abnormalities can be detected with karyotype and/or chromosome microarray (CMA).

	== Familial Forms ==		== Familial Forms ==