HAEM5:Systemic chronic active EBV disease - Revision history

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

2025-11-19T21:40:02Z

Genetic Diagnostic Testing Methods

← Older revision		Revision as of 16:40, 19 November 2025
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	\|Monoclonality detected in ~47% of cases<ref>{{Cite journal\|last=Kimura\|first=Hiroshi\|last2=Ito\|first2=Yoshinori\|last3=Kawabe\|first3=Shinji\|last4=Gotoh\|first4=Kensei\|last5=Takahashi\|first5=Yoshiyuki\|last6=Kojima\|first6=Seiji\|last7=Naoe\|first7=Tomoki\|last8=Esaki\|first8=Shinichi\|last9=Kikuta\|first9=Atsushi\|date=2012-01-19\|title=EBV-associated T/NK-cell lymphoproliferative diseases in nonimmunocompromised hosts: prospective analysis of 108 cases\|url=https://pubmed.ncbi.nlm.nih.gov/22096243\|journal=Blood\|volume=119\|issue=3\|pages=673–686\|doi=10.1182/blood-2011-10-381921\|issn=1528-0020\|pmid=22096243}}</ref>		\|Monoclonality detected in ~47% of cases<ref>{{Cite journal\|last=Kimura\|first=Hiroshi\|last2=Ito\|first2=Yoshinori\|last3=Kawabe\|first3=Shinji\|last4=Gotoh\|first4=Kensei\|last5=Takahashi\|first5=Yoshiyuki\|last6=Kojima\|first6=Seiji\|last7=Naoe\|first7=Tomoki\|last8=Esaki\|first8=Shinichi\|last9=Kikuta\|first9=Atsushi\|date=2012-01-19\|title=EBV-associated T/NK-cell lymphoproliferative diseases in nonimmunocompromised hosts: prospective analysis of 108 cases\|url=https://pubmed.ncbi.nlm.nih.gov/22096243\|journal=Blood\|volume=119\|issue=3\|pages=673–686\|doi=10.1182/blood-2011-10-381921\|issn=1528-0020\|pmid=22096243}}</ref>
	\|D		\|D
	\|The WHO 5<sup>th</sup> edition notes that, "cases with monomorphic and monoclonal proliferation have a poorer outcome than those with polymorphic and polyclonal proliferation."<ref name=":5" /><ref name=":0">{{Cite journal\|title=BlueBooksOnline\|url=https://tumourclassification.iarc.who.int/chapters/63}}</ref><ref>{{Cite journal\|last=Ohshima\|first=Koichi\|last2=Kimura\|first2=Hiroshi\|last3=Yoshino\|first3=Tadashi\|last4=Kim\|first4=Chul Woo\|last5=Ko\|first5=Young H.\|last6=Lee\|first6=Seung-Suk\|last7=Peh\|first7=Suat-Cheng\|last8=Chan\|first8=John K. C.\|last9=CAEBV Study Group\|date=2008-04\|title=Proposed categorization of pathological states of EBV-associated T/natural killer-cell lymphoproliferative disorder (LPD) in children and young adults: overlap with chronic active EBV infection and infantile fulminant EBV T-LPD\|url=https://pubmed.ncbi.nlm.nih.gov/18324913\|journal=Pathology International\|volume=58\|issue=4\|pages=209–217\|doi=10.1111/j.1440-1827.2008.02213.x\|issn=1440-1827\|pmid=18324913}}</ref>		\|The WHO 5<sup>th</sup> edition notes that, "cases with monomorphic and monoclonal proliferation have a poorer outcome than those with polymorphic and polyclonal proliferation."<ref name=":5">The WHO Classification of Tumours Editorial Board, ed. ''Haematolymphoid Tumours: Who Classification of Tumours''. 5th ed. International Agency for Research on Cancer; 2024.</ref><ref name=":0">{{Cite journal\|title=BlueBooksOnline\|url=https://tumourclassification.iarc.who.int/chapters/63}}</ref><ref>{{Cite journal\|last=Ohshima\|first=Koichi\|last2=Kimura\|first2=Hiroshi\|last3=Yoshino\|first3=Tadashi\|last4=Kim\|first4=Chul Woo\|last5=Ko\|first5=Young H.\|last6=Lee\|first6=Seung-Suk\|last7=Peh\|first7=Suat-Cheng\|last8=Chan\|first8=John K. C.\|last9=CAEBV Study Group\|date=2008-04\|title=Proposed categorization of pathological states of EBV-associated T/natural killer-cell lymphoproliferative disorder (LPD) in children and young adults: overlap with chronic active EBV infection and infantile fulminant EBV T-LPD\|url=https://pubmed.ncbi.nlm.nih.gov/18324913\|journal=Pathology International\|volume=58\|issue=4\|pages=209–217\|doi=10.1111/j.1440-1827.2008.02213.x\|issn=1440-1827\|pmid=18324913}}</ref>
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	\|}		\|}
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	==Genetic Diagnostic Testing Methods==		==Genetic Diagnostic Testing Methods==

	* ~~The~~ WHO 5<sup>th</sup> edition essential diagnostic criteria include:<ref name=":0" /><ref name=":5">The WHO Classification of Tumours Editorial Board, ed. ''Haematolymphoid Tumours: Who Classification of Tumours''. 5th ed. International Agency for Research on Cancer; 2024.</ref>		* '''Both the WHO 5<sup>th</sup> edition and International Consensus Classification (ICC) include detection of increased EBV DNA in the peripheral blood (>10,000 IU/mL in ICC criteria) and/or EBV RNA (EBER) or viral protein in T or NK-cells of affected tissues.'''<ref name=":5" />'''<ref name=":0" /><ref name=":1">Arber DA, Borowitz MJ, Cook JR, et al. ''The International Consensus Classification of Myeloid and Lymphoid Neoplasms''.; 2025.</ref>'''
	** Persistent (greater than 3 months) infectious mononucleosis-like symptoms
	** Increased EBV DNA in the peripheral blood or EBER-positive cells in affected organs with evidence of EBV infection in T or NK-cells
	** Exclusion of known immunodeficiency, malignancy, or autoimmune disorders

	* The International Consensus Classification (ICC) ~~revised diagnostic criteria~~ include~~:<ref name=":1">Arber DA, Borowitz MJ, Cook JR, et al. ''The International Consensus Classification~~ of ~~Myeloid and Lymphoid Neoplasms''.; 2025.</ref>~~
	** Persistent (greater than 3 months) infectious mononucleosis-like symptoms
	** Increased EBV DNA (>10,000 IU/mL~~) in the peripheral blood~~
	** Histologic evidence of organ disease
	** Detection of EBV RNA or viral protein in ~~T or NK-cells in affected tissues~~
	** Exclusion of known immunodeficiency, malignancy, or autoimmune disorders

	* '''Both the WHO 5<sup>th</sup> edition and ICC ~~include detection of increased EBV DNA in the peripheral blood~~ and/or EBV RNA (EBER) or viral protein in T or NK-cells of affected tissues.'''<ref name=":5" />'''<ref name=":0" /><ref name=":1" />'''
	** Whole blood or peripheral blood mononuclear cells are preferred for EBV DNA PCR testing, as serum or plasma are less sensitive for CAEBV disease<ref>{{Cite journal\|last=Kimura\|first=Hiroshi\|last2=Cohen\|first2=Jeffrey I.\|date=2017\|title=Chronic Active Epstein-Barr Virus Disease\|url=https://pubmed.ncbi.nlm.nih.gov/29375552\|journal=Frontiers in Immunology\|volume=8\|pages=1867\|doi=10.3389/fimmu.2017.01867\|issn=1664-3224\|pmc=5770746\|pmid=29375552}}</ref>		** Whole blood or peripheral blood mononuclear cells are preferred for EBV DNA PCR testing, as serum or plasma are less sensitive for CAEBV disease<ref>{{Cite journal\|last=Kimura\|first=Hiroshi\|last2=Cohen\|first2=Jeffrey I.\|date=2017\|title=Chronic Active Epstein-Barr Virus Disease\|url=https://pubmed.ncbi.nlm.nih.gov/29375552\|journal=Frontiers in Immunology\|volume=8\|pages=1867\|doi=10.3389/fimmu.2017.01867\|issn=1664-3224\|pmc=5770746\|pmid=29375552}}</ref>
	** In tissues, using a double stain for B, T, or NK-cell markers and EBV is recommended.		** In tissues, using a double stain for B, T, or NK-cell markers and EBV is recommended.
	* TCR-gene rearrangements can be tested via PCR or NGS methods.
	* DNA mutations (SNV/Indels) can be detected using NGS

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

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

2025-11-19T02:11:39Z

Gene Mutations (SNV/INDEL)

← Older revision		Revision as of 21:11, 18 November 2025
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	[[HAEM5:Table_of_Contents\|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]		[[HAEM5:Table_of_Contents\|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]

	==Primary Author(s)*==		==Primary Author(s)* ==

	Karin Miller, MD<span style="color:#0070C0"> </span>		Karin Miller, MD<span style="color:#0070C0"> </span>

Karin.Miller: /* Additional Information */

2025-11-19T01:40:46Z

Additional Information

← Older revision		Revision as of 20:40, 18 November 2025
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	==Additional Information==		==Additional Information==

	* CAEBV shows an increased prevalence in populations from Asia and ~~natives from Central and South~~ America, suggesting a potential for genetic polymorphisms in immune-modulating genes to play a role in disease pathogenesis.<ref>{{Cite journal\|last=Kimura\|first=Hiroshi\|last2=Cohen\|first2=Jeffrey I.\|date=2017\|title=Chronic Active Epstein-Barr Virus Disease\|url=https://pubmed.ncbi.nlm.nih.gov/29375552\|journal=Frontiers in Immunology\|volume=8\|pages=1867\|doi=10.3389/fimmu.2017.01867\|issn=1664-3224\|pmc=5770746\|pmid=29375552}}</ref> <ref>{{Cite journal\|last=Kimura\|first=Hiroshi\|date=2006\|title=Pathogenesis of chronic active Epstein-Barr virus infection: is this an infectious disease, lymphoproliferative disorder, or immunodeficiency?\|url=https://pubmed.ncbi.nlm.nih.gov/16791843\|journal=Reviews in Medical Virology\|volume=16\|issue=4\|pages=251–261\|doi=10.1002/rmv.505\|issn=1052-9276\|pmid=16791843}}</ref>		* CAEBV shows an increased prevalence in populations from Asia and Latin America, suggesting a potential for genetic polymorphisms in immune-modulating genes to play a role in disease pathogenesis.<ref>{{Cite journal\|last=Kimura\|first=Hiroshi\|last2=Cohen\|first2=Jeffrey I.\|date=2017\|title=Chronic Active Epstein-Barr Virus Disease\|url=https://pubmed.ncbi.nlm.nih.gov/29375552\|journal=Frontiers in Immunology\|volume=8\|pages=1867\|doi=10.3389/fimmu.2017.01867\|issn=1664-3224\|pmc=5770746\|pmid=29375552}}</ref> <ref>{{Cite journal\|last=Kimura\|first=Hiroshi\|date=2006\|title=Pathogenesis of chronic active Epstein-Barr virus infection: is this an infectious disease, lymphoproliferative disorder, or immunodeficiency?\|url=https://pubmed.ncbi.nlm.nih.gov/16791843\|journal=Reviews in Medical Virology\|volume=16\|issue=4\|pages=251–261\|doi=10.1002/rmv.505\|issn=1052-9276\|pmid=16791843}}</ref>
	* EBV clonality testing showed monoclonality (84%), oligoclonality (11%), or polyclonality (5%).<ref>{{Cite journal\|last=Kimura\|first=Hiroshi\|last2=Ito\|first2=Yoshinori\|last3=Kawabe\|first3=Shinji\|last4=Gotoh\|first4=Kensei\|last5=Takahashi\|first5=Yoshiyuki\|last6=Kojima\|first6=Seiji\|last7=Naoe\|first7=Tomoki\|last8=Esaki\|first8=Shinichi\|last9=Kikuta\|first9=Atsushi\|date=2012-01-19\|title=EBV-associated T/NK-cell lymphoproliferative diseases in nonimmunocompromised hosts: prospective analysis of 108 cases\|url=https://pubmed.ncbi.nlm.nih.gov/22096243\|journal=Blood\|volume=119\|issue=3\|pages=673–686\|doi=10.1182/blood-2011-10-381921\|issn=1528-0020\|pmid=22096243}}</ref> TCR clonality testing is described above (see gene rearrangements)		* EBV clonality testing showed monoclonality (84%), oligoclonality (11%), or polyclonality (5%).<ref>{{Cite journal\|last=Kimura\|first=Hiroshi\|last2=Ito\|first2=Yoshinori\|last3=Kawabe\|first3=Shinji\|last4=Gotoh\|first4=Kensei\|last5=Takahashi\|first5=Yoshiyuki\|last6=Kojima\|first6=Seiji\|last7=Naoe\|first7=Tomoki\|last8=Esaki\|first8=Shinichi\|last9=Kikuta\|first9=Atsushi\|date=2012-01-19\|title=EBV-associated T/NK-cell lymphoproliferative diseases in nonimmunocompromised hosts: prospective analysis of 108 cases\|url=https://pubmed.ncbi.nlm.nih.gov/22096243\|journal=Blood\|volume=119\|issue=3\|pages=673–686\|doi=10.1182/blood-2011-10-381921\|issn=1528-0020\|pmid=22096243}}</ref> TCR clonality testing is described above (see gene rearrangements)

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

2025-11-19T01:37:21Z

Gene Mutations (SNV/INDEL)

← Older revision		Revision as of 20:37, 18 November 2025
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	* Somatic mutations can be detected in a subset of CAEBV cases (~29%).<ref name=":2">{{Cite journal\|last=Okuno\|first=Yusuke\|last2=Murata\|first2=Takayuki\|last3=Sato\|first3=Yoshitaka\|last4=Muramatsu\|first4=Hideki\|last5=Ito\|first5=Yoshinori\|last6=Watanabe\|first6=Takahiro\|last7=Okuno\|first7=Tatsuya\|last8=Murakami\|first8=Norihiro\|last9=Yoshida\|first9=Kenichi\|date=2019-03\|title=Defective Epstein-Barr virus in chronic active infection and haematological malignancy\|url=https://pubmed.ncbi.nlm.nih.gov/30664667\|journal=Nature Microbiology\|volume=4\|issue=3\|pages=404–413\|doi=10.1038/s41564-018-0334-0\|issn=2058-5276\|pmid=30664667}}</ref>		* Somatic mutations can be detected in a subset of CAEBV cases (~29%).<ref name=":2">{{Cite journal\|last=Okuno\|first=Yusuke\|last2=Murata\|first2=Takayuki\|last3=Sato\|first3=Yoshitaka\|last4=Muramatsu\|first4=Hideki\|last5=Ito\|first5=Yoshinori\|last6=Watanabe\|first6=Takahiro\|last7=Okuno\|first7=Tatsuya\|last8=Murakami\|first8=Norihiro\|last9=Yoshida\|first9=Kenichi\|date=2019-03\|title=Defective Epstein-Barr virus in chronic active infection and haematological malignancy\|url=https://pubmed.ncbi.nlm.nih.gov/30664667\|journal=Nature Microbiology\|volume=4\|issue=3\|pages=404–413\|doi=10.1038/s41564-018-0334-0\|issn=2058-5276\|pmid=30664667}}</ref>
	* ''DDX3X'' mutations are the most commonly implicated known driver mutations. <ref name=":2" />		* ''DDX3X'' mutations are the most commonly implicated known driver mutations. <ref name=":2" />
	** Mutations in KMT2D,KMT2B, BCOR/BCORL1, TET2, KDM6A, NFKB1, and ARID1a have also been described.<ref name=":2" /><ref>{{Cite journal\|last=Akazawa\|first=Ryo\|last2=Mikami\|first2=Takashi\|last3=Yamada\|first3=Masaki\|last4=Kato\|first4=Itaru\|last5=Kubota\|first5=Hirohito\|last6=Saida\|first6=Satoshi\|last7=Uchihara\|first7=Yoshinori\|last8=Ishikawa\|first8=Yuriko\|last9=Kamitori\|first9=Tatsuya\|date=2025-11-06\|title=Multiomics analysis reveals the genetic and epigenetic features of high-risk NK cell-type chronic active EBV infection\|url=https://pubmed.ncbi.nlm.nih.gov/40737598\|journal=Blood\|volume=146\|issue=19\|pages=2336–2349\|doi=10.1182/blood.2024026805\|issn=1528-0020\|pmid=40737598}}</ref>		** Mutations in KMT2D, KMT2B, BCOR/BCORL1, TET2, KDM6A, NFKB1, and ARID1a have also been described.<ref name=":2" /><ref>{{Cite journal\|last=Akazawa\|first=Ryo\|last2=Mikami\|first2=Takashi\|last3=Yamada\|first3=Masaki\|last4=Kato\|first4=Itaru\|last5=Kubota\|first5=Hirohito\|last6=Saida\|first6=Satoshi\|last7=Uchihara\|first7=Yoshinori\|last8=Ishikawa\|first8=Yuriko\|last9=Kamitori\|first9=Tatsuya\|date=2025-11-06\|title=Multiomics analysis reveals the genetic and epigenetic features of high-risk NK cell-type chronic active EBV infection\|url=https://pubmed.ncbi.nlm.nih.gov/40737598\|journal=Blood\|volume=146\|issue=19\|pages=2336–2349\|doi=10.1182/blood.2024026805\|issn=1528-0020\|pmid=40737598}}</ref>
	* In one study, identical driver mutations were detected in different cell lineages (T, B, and NK), demonstrating that EBV infected a common lymphoid progenitor in CAEBV patients. Acquisition of somatic, driver mutations in these pre-malignant, EBV-infected cells subsequently leads to clonal evolution in multiple cell lines.<ref name=":2" />		* In one study, identical driver mutations were detected in different cell lineages (T, B, and NK), demonstrating that EBV infected a common lymphoid progenitor in CAEBV patients. Acquisition of somatic, driver mutations in these pre-malignant, EBV-infected cells subsequently leads to clonal evolution in multiple cell lines.<ref name=":2" />
	* Presence of a driver mutation associated with shorter overall survival<ref name=":2" />		* Presence of a driver mutation associated with shorter overall survival<ref name=":2" />

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

2025-11-18T21:49:18Z

Primary Author(s)*

← Older revision		Revision as of 16:49, 18 November 2025
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	\|Monoclonality detected in ~47% of cases<ref>{{Cite journal\|last=Kimura\|first=Hiroshi\|last2=Ito\|first2=Yoshinori\|last3=Kawabe\|first3=Shinji\|last4=Gotoh\|first4=Kensei\|last5=Takahashi\|first5=Yoshiyuki\|last6=Kojima\|first6=Seiji\|last7=Naoe\|first7=Tomoki\|last8=Esaki\|first8=Shinichi\|last9=Kikuta\|first9=Atsushi\|date=2012-01-19\|title=EBV-associated T/NK-cell lymphoproliferative diseases in nonimmunocompromised hosts: prospective analysis of 108 cases\|url=https://pubmed.ncbi.nlm.nih.gov/22096243\|journal=Blood\|volume=119\|issue=3\|pages=673–686\|doi=10.1182/blood-2011-10-381921\|issn=1528-0020\|pmid=22096243}}</ref>		\|Monoclonality detected in ~47% of cases<ref>{{Cite journal\|last=Kimura\|first=Hiroshi\|last2=Ito\|first2=Yoshinori\|last3=Kawabe\|first3=Shinji\|last4=Gotoh\|first4=Kensei\|last5=Takahashi\|first5=Yoshiyuki\|last6=Kojima\|first6=Seiji\|last7=Naoe\|first7=Tomoki\|last8=Esaki\|first8=Shinichi\|last9=Kikuta\|first9=Atsushi\|date=2012-01-19\|title=EBV-associated T/NK-cell lymphoproliferative diseases in nonimmunocompromised hosts: prospective analysis of 108 cases\|url=https://pubmed.ncbi.nlm.nih.gov/22096243\|journal=Blood\|volume=119\|issue=3\|pages=673–686\|doi=10.1182/blood-2011-10-381921\|issn=1528-0020\|pmid=22096243}}</ref>
	\|D		\|D
	\|The WHO 5<sup>th</sup> edition notes that, "cases with monomorphic and monoclonal proliferation have a poorer outcome than those with polymorphic and polyclonal proliferation."<ref name=":0">{{Cite journal\|title=BlueBooksOnline\|url=https://tumourclassification.iarc.who.int/chapters/63}}</ref><ref>{{Cite journal\|last=Ohshima\|first=Koichi\|last2=Kimura\|first2=Hiroshi\|last3=Yoshino\|first3=Tadashi\|last4=Kim\|first4=Chul Woo\|last5=Ko\|first5=Young H.\|last6=Lee\|first6=Seung-Suk\|last7=Peh\|first7=Suat-Cheng\|last8=Chan\|first8=John K. C.\|last9=CAEBV Study Group\|date=2008-04\|title=Proposed categorization of pathological states of EBV-associated T/natural killer-cell lymphoproliferative disorder (LPD) in children and young adults: overlap with chronic active EBV infection and infantile fulminant EBV T-LPD\|url=https://pubmed.ncbi.nlm.nih.gov/18324913\|journal=Pathology International\|volume=58\|issue=4\|pages=209–217\|doi=10.1111/j.1440-1827.2008.02213.x\|issn=1440-1827\|pmid=18324913}}</ref>		\|The WHO 5<sup>th</sup> edition notes that, "cases with monomorphic and monoclonal proliferation have a poorer outcome than those with polymorphic and polyclonal proliferation."<ref name=":5" /><ref name=":0">{{Cite journal\|title=BlueBooksOnline\|url=https://tumourclassification.iarc.who.int/chapters/63}}</ref><ref>{{Cite journal\|last=Ohshima\|first=Koichi\|last2=Kimura\|first2=Hiroshi\|last3=Yoshino\|first3=Tadashi\|last4=Kim\|first4=Chul Woo\|last5=Ko\|first5=Young H.\|last6=Lee\|first6=Seung-Suk\|last7=Peh\|first7=Suat-Cheng\|last8=Chan\|first8=John K. C.\|last9=CAEBV Study Group\|date=2008-04\|title=Proposed categorization of pathological states of EBV-associated T/natural killer-cell lymphoproliferative disorder (LPD) in children and young adults: overlap with chronic active EBV infection and infantile fulminant EBV T-LPD\|url=https://pubmed.ncbi.nlm.nih.gov/18324913\|journal=Pathology International\|volume=58\|issue=4\|pages=209–217\|doi=10.1111/j.1440-1827.2008.02213.x\|issn=1440-1827\|pmid=18324913}}</ref>
	\|N/A		\|N/A
	\|}		\|}

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

2025-11-18T21:48:39Z

Primary Author(s)*

← Older revision		Revision as of 16:48, 18 November 2025
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	==Genetic Diagnostic Testing Methods==		==Genetic Diagnostic Testing Methods==

	* The WHO 5<sup>th</sup> edition essential diagnostic criteria include:<ref name=":0" />		* The WHO 5<sup>th</sup> edition essential diagnostic criteria include:<ref name=":0" /><ref name=":5">The WHO Classification of Tumours Editorial Board, ed. ''Haematolymphoid Tumours: Who Classification of Tumours''. 5th ed. International Agency for Research on Cancer; 2024.</ref>
	** Persistent (greater than 3 months) infectious mononucleosis-like symptoms		** Persistent (greater than 3 months) infectious mononucleosis-like symptoms
	** Increased EBV DNA in the peripheral blood or EBER-positive cells in affected organs with evidence of EBV infection in T or NK-cells		** Increased EBV DNA in the peripheral blood or EBER-positive cells in affected organs with evidence of EBV infection in T or NK-cells
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	** Exclusion of known immunodeficiency, malignancy, or autoimmune disorders		** Exclusion of known immunodeficiency, malignancy, or autoimmune disorders

	* '''Both the WHO 5<sup>th</sup> edition and ICC include detection of increased EBV DNA in the peripheral blood and/or EBV RNA (EBER) or viral protein in T or NK-cells of affected tissues.<ref name=":0" /><ref name=":1" />'''		* '''Both the WHO 5<sup>th</sup> edition and ICC include detection of increased EBV DNA in the peripheral blood and/or EBV RNA (EBER) or viral protein in T or NK-cells of affected tissues.'''<ref name=":5" />'''<ref name=":0" /><ref name=":1" />'''
	** Whole blood or peripheral blood mononuclear cells are preferred for EBV DNA PCR testing, as serum or plasma are less sensitive for CAEBV disease<ref>{{Cite journal\|last=Kimura\|first=Hiroshi\|last2=Cohen\|first2=Jeffrey I.\|date=2017\|title=Chronic Active Epstein-Barr Virus Disease\|url=https://pubmed.ncbi.nlm.nih.gov/29375552\|journal=Frontiers in Immunology\|volume=8\|pages=1867\|doi=10.3389/fimmu.2017.01867\|issn=1664-3224\|pmc=5770746\|pmid=29375552}}</ref>		** Whole blood or peripheral blood mononuclear cells are preferred for EBV DNA PCR testing, as serum or plasma are less sensitive for CAEBV disease<ref>{{Cite journal\|last=Kimura\|first=Hiroshi\|last2=Cohen\|first2=Jeffrey I.\|date=2017\|title=Chronic Active Epstein-Barr Virus Disease\|url=https://pubmed.ncbi.nlm.nih.gov/29375552\|journal=Frontiers in Immunology\|volume=8\|pages=1867\|doi=10.3389/fimmu.2017.01867\|issn=1664-3224\|pmc=5770746\|pmid=29375552}}</ref>
	** In tissues, using a double stain for B, T, or NK-cell markers and EBV is recommended.		** In tissues, using a double stain for B, T, or NK-cell markers and EBV is recommended.

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

2025-11-18T20:44:31Z

Genetic Diagnostic Testing Methods

← Older revision		Revision as of 15:44, 18 November 2025
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	** Whole blood or peripheral blood mononuclear cells are preferred for EBV DNA PCR testing, as serum or plasma are less sensitive for CAEBV disease<ref>{{Cite journal\|last=Kimura\|first=Hiroshi\|last2=Cohen\|first2=Jeffrey I.\|date=2017\|title=Chronic Active Epstein-Barr Virus Disease\|url=https://pubmed.ncbi.nlm.nih.gov/29375552\|journal=Frontiers in Immunology\|volume=8\|pages=1867\|doi=10.3389/fimmu.2017.01867\|issn=1664-3224\|pmc=5770746\|pmid=29375552}}</ref>		** Whole blood or peripheral blood mononuclear cells are preferred for EBV DNA PCR testing, as serum or plasma are less sensitive for CAEBV disease<ref>{{Cite journal\|last=Kimura\|first=Hiroshi\|last2=Cohen\|first2=Jeffrey I.\|date=2017\|title=Chronic Active Epstein-Barr Virus Disease\|url=https://pubmed.ncbi.nlm.nih.gov/29375552\|journal=Frontiers in Immunology\|volume=8\|pages=1867\|doi=10.3389/fimmu.2017.01867\|issn=1664-3224\|pmc=5770746\|pmid=29375552}}</ref>
	** In tissues, using a double stain for B, T, or NK-cell markers and EBV is recommended.		** In tissues, using a double stain for B, T, or NK-cell markers and EBV is recommended.
	* TCR-gene rearrangements can be tested via PCR~~-Capillary Electrophoresis~~ or NGS methods		* TCR-gene rearrangements can be tested via PCR or NGS methods.
	* DNA mutations (SNV/Indels) can be detected using NGS		* DNA mutations (SNV/Indels) can be detected using NGS

Karin.Miller: /* Individual Region Genomic Gain/Loss/LOH */

2025-11-18T20:43:35Z

Individual Region Genomic Gain/Loss/LOH

← Older revision		Revision as of 15:43, 18 November 2025
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	* Multiple different chromosomal aberrations have been reported, approximately 7% of cases<ref>{{Cite journal\|last=Kimura\|first=Hiroshi\|last2=Ito\|first2=Yoshinori\|last3=Kawabe\|first3=Shinji\|last4=Gotoh\|first4=Kensei\|last5=Takahashi\|first5=Yoshiyuki\|last6=Kojima\|first6=Seiji\|last7=Naoe\|first7=Tomoki\|last8=Esaki\|first8=Shinichi\|last9=Kikuta\|first9=Atsushi\|date=2012-01-19\|title=EBV-associated T/NK-cell lymphoproliferative diseases in nonimmunocompromised hosts: prospective analysis of 108 cases\|url=https://pubmed.ncbi.nlm.nih.gov/22096243\|journal=Blood\|volume=119\|issue=3\|pages=673–686\|doi=10.1182/blood-2011-10-381921\|issn=1528-0020\|pmid=22096243}}</ref>		* Multiple different chromosomal aberrations have been reported, approximately 7% of cases<ref>{{Cite journal\|last=Kimura\|first=Hiroshi\|last2=Ito\|first2=Yoshinori\|last3=Kawabe\|first3=Shinji\|last4=Gotoh\|first4=Kensei\|last5=Takahashi\|first5=Yoshiyuki\|last6=Kojima\|first6=Seiji\|last7=Naoe\|first7=Tomoki\|last8=Esaki\|first8=Shinichi\|last9=Kikuta\|first9=Atsushi\|date=2012-01-19\|title=EBV-associated T/NK-cell lymphoproliferative diseases in nonimmunocompromised hosts: prospective analysis of 108 cases\|url=https://pubmed.ncbi.nlm.nih.gov/22096243\|journal=Blood\|volume=119\|issue=3\|pages=673–686\|doi=10.1182/blood-2011-10-381921\|issn=1528-0020\|pmid=22096243}}</ref>
	* Frequent copy number alterations have recently been described in a subtype of NK-cell CAEBV with a poor prognosis that also showed a high CPG-island methylation pattern and higher tumor mutational burden (TMB).<ref name=":4" />		* Frequent copy number alterations (CNAs) have recently been described in a subtype of NK-cell CAEBV with a poor prognosis that also showed a high CPG-island methylation pattern and higher tumor mutational burden (TMB).<ref name=":4" />

	*Intragenic deletions in the EBV genome may be detected (~35% of cases)<ref name=":2" />. Intragenic deletions in EBV were also detected in other EBV-associated neoplasms, but were not reported in patients with infectious mononucleosis or posttransplant lymphoproliferative disorder (PTLD)<ref name=":2" />		*Intragenic deletions in the EBV genome may be detected (~35% of cases)<ref name=":2" />. Intragenic deletions in EBV were also detected in other EBV-associated neoplasms, but were not reported in patients with infectious mononucleosis or posttransplant lymphoproliferative disorder (PTLD)<ref name=":2" />

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

2025-11-18T20:42:50Z

Gene Mutations (SNV/INDEL)

← Older revision		Revision as of 15:42, 18 November 2025
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	* Somatic mutations can be detected in a subset of CAEBV cases (~29%).<ref name=":2">{{Cite journal\|last=Okuno\|first=Yusuke\|last2=Murata\|first2=Takayuki\|last3=Sato\|first3=Yoshitaka\|last4=Muramatsu\|first4=Hideki\|last5=Ito\|first5=Yoshinori\|last6=Watanabe\|first6=Takahiro\|last7=Okuno\|first7=Tatsuya\|last8=Murakami\|first8=Norihiro\|last9=Yoshida\|first9=Kenichi\|date=2019-03\|title=Defective Epstein-Barr virus in chronic active infection and haematological malignancy\|url=https://pubmed.ncbi.nlm.nih.gov/30664667\|journal=Nature Microbiology\|volume=4\|issue=3\|pages=404–413\|doi=10.1038/s41564-018-0334-0\|issn=2058-5276\|pmid=30664667}}</ref>		* Somatic mutations can be detected in a subset of CAEBV cases (~29%).<ref name=":2">{{Cite journal\|last=Okuno\|first=Yusuke\|last2=Murata\|first2=Takayuki\|last3=Sato\|first3=Yoshitaka\|last4=Muramatsu\|first4=Hideki\|last5=Ito\|first5=Yoshinori\|last6=Watanabe\|first6=Takahiro\|last7=Okuno\|first7=Tatsuya\|last8=Murakami\|first8=Norihiro\|last9=Yoshida\|first9=Kenichi\|date=2019-03\|title=Defective Epstein-Barr virus in chronic active infection and haematological malignancy\|url=https://pubmed.ncbi.nlm.nih.gov/30664667\|journal=Nature Microbiology\|volume=4\|issue=3\|pages=404–413\|doi=10.1038/s41564-018-0334-0\|issn=2058-5276\|pmid=30664667}}</ref>
	* ''DDX3X'' mutations are the most commonly implicated known driver mutations. <ref name=":2" />		* ''DDX3X'' mutations are the most commonly implicated known driver mutations. <ref name=":2" />
	** Mutations in KMT2D, BCOR/BCORL1, TET2, KDM6A~~, KMT2B~~, NFKB1, and ARID1a have also been described.<ref name=":2" /><ref>{{Cite journal\|last=Akazawa\|first=Ryo\|last2=Mikami\|first2=Takashi\|last3=Yamada\|first3=Masaki\|last4=Kato\|first4=Itaru\|last5=Kubota\|first5=Hirohito\|last6=Saida\|first6=Satoshi\|last7=Uchihara\|first7=Yoshinori\|last8=Ishikawa\|first8=Yuriko\|last9=Kamitori\|first9=Tatsuya\|date=2025-11-06\|title=Multiomics analysis reveals the genetic and epigenetic features of high-risk NK cell-type chronic active EBV infection\|url=https://pubmed.ncbi.nlm.nih.gov/40737598\|journal=Blood\|volume=146\|issue=19\|pages=2336–2349\|doi=10.1182/blood.2024026805\|issn=1528-0020\|pmid=40737598}}</ref>		** Mutations in KMT2D,KMT2B, BCOR/BCORL1, TET2, KDM6A, NFKB1, and ARID1a have also been described.<ref name=":2" /><ref>{{Cite journal\|last=Akazawa\|first=Ryo\|last2=Mikami\|first2=Takashi\|last3=Yamada\|first3=Masaki\|last4=Kato\|first4=Itaru\|last5=Kubota\|first5=Hirohito\|last6=Saida\|first6=Satoshi\|last7=Uchihara\|first7=Yoshinori\|last8=Ishikawa\|first8=Yuriko\|last9=Kamitori\|first9=Tatsuya\|date=2025-11-06\|title=Multiomics analysis reveals the genetic and epigenetic features of high-risk NK cell-type chronic active EBV infection\|url=https://pubmed.ncbi.nlm.nih.gov/40737598\|journal=Blood\|volume=146\|issue=19\|pages=2336–2349\|doi=10.1182/blood.2024026805\|issn=1528-0020\|pmid=40737598}}</ref>
	* In one study, identical driver mutations were detected in different cell lineages (T, B, and NK), demonstrating that EBV infected a common lymphoid progenitor in CAEBV patients. Acquisition of somatic, driver mutations in these pre-malignant, EBV-infected cells subsequently leads to clonal evolution in multiple cell lines.<ref name=":2" />		* In one study, identical driver mutations were detected in different cell lineages (T, B, and NK), demonstrating that EBV infected a common lymphoid progenitor in CAEBV patients. Acquisition of somatic, driver mutations in these pre-malignant, EBV-infected cells subsequently leads to clonal evolution in multiple cell lines.<ref name=":2" />
	* Presence of a driver mutation associated with shorter overall survival<ref name=":2" />		* Presence of a driver mutation associated with shorter overall survival<ref name=":2" />

Karin.Miller: /* Gene Rearrangements */

2025-11-18T20:41:49Z

Gene Rearrangements

← Older revision		Revision as of 15:41, 18 November 2025
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	* Somatic mutations can be detected in a subset of CAEBV cases (~29%).<ref name=":2">{{Cite journal\|last=Okuno\|first=Yusuke\|last2=Murata\|first2=Takayuki\|last3=Sato\|first3=Yoshitaka\|last4=Muramatsu\|first4=Hideki\|last5=Ito\|first5=Yoshinori\|last6=Watanabe\|first6=Takahiro\|last7=Okuno\|first7=Tatsuya\|last8=Murakami\|first8=Norihiro\|last9=Yoshida\|first9=Kenichi\|date=2019-03\|title=Defective Epstein-Barr virus in chronic active infection and haematological malignancy\|url=https://pubmed.ncbi.nlm.nih.gov/30664667\|journal=Nature Microbiology\|volume=4\|issue=3\|pages=404–413\|doi=10.1038/s41564-018-0334-0\|issn=2058-5276\|pmid=30664667}}</ref>		* Somatic mutations can be detected in a subset of CAEBV cases (~29%).<ref name=":2">{{Cite journal\|last=Okuno\|first=Yusuke\|last2=Murata\|first2=Takayuki\|last3=Sato\|first3=Yoshitaka\|last4=Muramatsu\|first4=Hideki\|last5=Ito\|first5=Yoshinori\|last6=Watanabe\|first6=Takahiro\|last7=Okuno\|first7=Tatsuya\|last8=Murakami\|first8=Norihiro\|last9=Yoshida\|first9=Kenichi\|date=2019-03\|title=Defective Epstein-Barr virus in chronic active infection and haematological malignancy\|url=https://pubmed.ncbi.nlm.nih.gov/30664667\|journal=Nature Microbiology\|volume=4\|issue=3\|pages=404–413\|doi=10.1038/s41564-018-0334-0\|issn=2058-5276\|pmid=30664667}}</ref>
	* ''DDX3X'' mutations are the most commonly implicated known driver mutations<ref name=":2" />		* ''DDX3X'' mutations are the most commonly implicated known driver mutations. <ref name=":2" />
			** Mutations in KMT2D, BCOR/BCORL1, TET2, KDM6A, KMT2B, NFKB1, and ARID1a have also been described.<ref name=":2" /><ref>{{Cite journal\|last=Akazawa\|first=Ryo\|last2=Mikami\|first2=Takashi\|last3=Yamada\|first3=Masaki\|last4=Kato\|first4=Itaru\|last5=Kubota\|first5=Hirohito\|last6=Saida\|first6=Satoshi\|last7=Uchihara\|first7=Yoshinori\|last8=Ishikawa\|first8=Yuriko\|last9=Kamitori\|first9=Tatsuya\|date=2025-11-06\|title=Multiomics analysis reveals the genetic and epigenetic features of high-risk NK cell-type chronic active EBV infection\|url=https://pubmed.ncbi.nlm.nih.gov/40737598\|journal=Blood\|volume=146\|issue=19\|pages=2336–2349\|doi=10.1182/blood.2024026805\|issn=1528-0020\|pmid=40737598}}</ref>
	* In one study, identical driver mutations were detected in different cell lineages (T, B, and NK), demonstrating that EBV infected a common lymphoid progenitor in CAEBV patients. Acquisition of somatic, driver mutations in these pre-malignant, EBV-infected cells subsequently leads to clonal evolution in multiple cell lines.<ref name=":2" />		* In one study, identical driver mutations were detected in different cell lineages (T, B, and NK), demonstrating that EBV infected a common lymphoid progenitor in CAEBV patients. Acquisition of somatic, driver mutations in these pre-malignant, EBV-infected cells subsequently leads to clonal evolution in multiple cell lines.<ref name=":2" />
	* Presence of a driver mutation associated with shorter overall survival<ref name=":2" />		* Presence of a driver mutation associated with shorter overall survival<ref name=":2" />
	* Mutations in DDX3X, KMT2D, BCOR/BCORL1, TET2, and KDM6A have been described.<ref name=":2" /> Mutations in KMT2B, NFKB1, and ARID1a have also recently been described.<ref>{{Cite journal\|last=Akazawa\|first=Ryo\|last2=Mikami\|first2=Takashi\|last3=Yamada\|first3=Masaki\|last4=Kato\|first4=Itaru\|last5=Kubota\|first5=Hirohito\|last6=Saida\|first6=Satoshi\|last7=Uchihara\|first7=Yoshinori\|last8=Ishikawa\|first8=Yuriko\|last9=Kamitori\|first9=Tatsuya\|date=2025-11-06\|title=Multiomics analysis reveals the genetic and epigenetic features of high-risk NK cell-type chronic active EBV infection\|url=https://pubmed.ncbi.nlm.nih.gov/40737598\|journal=Blood\|volume=146\|issue=19\|pages=2336–2349\|doi=10.1182/blood.2024026805\|issn=1528-0020\|pmid=40737598}}</ref>

	{\| class="wikitable sortable"		{\| class="wikitable sortable"