Compendium of Cancer Genome Aberrations

HAEM5:Systemic chronic active EBV disease: Difference between revisions

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[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]


{{Under Construction}}
==Primary Author(s)* ==
 
<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], 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 to a table, click within the table and select the > symbol that appears to be given options. 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)*==
 
Put your text here<span style="color:#0070C0"> (''<span class="blue-text">EXAMPLE:</span>'' Jane Smith, PhD) </span>
 
__TOC__


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


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|}
|}


==Definition / Description of Disease==
==Related Terminology==


Put your text here <span style="color:#0070C0">(''Instructions: Brief description of approximately one paragraph - include disease context relative to other WHO classification categories, diagnostic criteria if applicable, and differential diagnosis if applicable. Other classifications can be referenced for comparison.'') </span>
==Synonyms / Terminology==
Put your text here <span style="color:#0070C0">(''Instructions: Include currently used terms and major historical ones, adding “(historical)” after the latter.'') </span>
==Epidemiology / Prevalence==
Put your text here
==Clinical Features==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
{| class="wikitable"
{| class="wikitable"
|'''Signs and Symptoms'''
|+
|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
|Acceptable
|N/A
|-
|Not Recommended
|Chronic active EBV infection; severe chronic active EBV infection; chronic active EBV disease (T- and NK-cell phenotype); chronic active EBV infection of T- and NK-cell type, systemic form
|}


<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
==Gene Rearrangements==
 
Approximately half of CAEBV cases show monoclonal T-cell gene rearrangements.
<span class="blue-text">EXAMPLE:</span> Fatigue
{| class="wikitable sortable"
 
|-
<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|'''Laboratory Findings'''
|T-cell Receptor (TCR) Gene Rearrangements||N/A||V(D)J rearrangement of T-cell receptor loci <ref>{{Cite journal|last=van Dongen|first=J. J. M.|last2=Langerak|first2=A. W.|last3=Brüggemann|first3=M.|last4=Evans|first4=P. a. S.|last5=Hummel|first5=M.|last6=Lavender|first6=F. L.|last7=Delabesse|first7=E.|last8=Davi|first8=F.|last9=Schuuring|first9=E.|date=2003-12|title=Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936|url=https://pubmed.ncbi.nlm.nih.gov/14671650|journal=Leukemia|volume=17|issue=12|pages=2257–2317|doi=10.1038/sj.leu.2403202|issn=0887-6924|pmid=14671650}}</ref>||N/A
|<span class="blue-text">EXAMPLE:</span> Cytopenias
|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
<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
|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>
|N/A
|}
|}
==Individual Region Genomic Gain/Loss/LOH==


==Sites of Involvement==
* 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 (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" />
Put your text here <span style="color:#0070C0">(''Instruction: Indicate physical sites; <span class="blue-text">EXAMPLE:</span> nodal, extranodal, bone marrow'') </span>


==Morphologic Features==
*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" />
 
Put your text here
 
==Immunophenotype==
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>


{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Finding!!Marker
!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|Positive (universal)||<span class="blue-text">EXAMPLE:</span> CD1
|N/A
|N/A
|N/A
|N/A
|N/A
|N/A
|N/A
|}
==Characteristic Chromosomal or Other Global Mutational Patterns==
N/A
{| class="wikitable sortable"
|-
|-
|Positive (subset)||<span class="blue-text">EXAMPLE:</span> CD2
!Chromosomal Pattern
|-
!Molecular Pathogenesis
|Negative (universal)||<span class="blue-text">EXAMPLE:</span> CD3
!Prevalence -  
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|Negative (subset)||<span class="blue-text">EXAMPLE:</span> CD4
|N/A
|N/A
|N/A
|N.A
|N/A
|N/A
|}
|}
==Gene Mutations (SNV/INDEL)==


==Chromosomal Rearrangements (Gene Fusions)==
* 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" />
Put your text here and fill in the table
** 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" />
* Presence of a driver mutation associated with shorter overall survival<ref name=":2" />


{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
!Diagnostic Significance (Yes, No or Unknown)
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Prognostic Significance (Yes, No or Unknown)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  
!Therapeutic Significance (Yes, No or Unknown)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)||<span class="blue-text">EXAMPLE:</span> 3'ABL1 / 5'BCR||<span class="blue-text">EXAMPLE:</span> der(22)||<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
|DDX3X
<span class="blue-text">EXAMPLE:</span> 30% (add reference)
|Truncating mutations and pathogenic missense and in-frame deletions have been reported <ref name=":2" />
|Yes
|TSG<ref name=":3">{{Cite journal|title=OncoKB™ - MSK's Precision Oncology Knowledge Base|url=https://www.oncokb.org/|language=en}}</ref>
|Recurrent (~18%)<ref name=":2" />
|D, P
|No
|No
|Yes
|Presence of a driver mutation associated with shorter overall survival<ref name=":2" />  
|<span class="blue-text">EXAMPLE:</span>
 
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
|}
==Individual Region Genomic Gain / Loss / LOH==
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.'') </span>
 
{| class="wikitable sortable"
|-
|-
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
|KMT2D
!Diagnostic Significance (Yes, No or Unknown)
|Truncating mutations<ref name=":2" />
!Prognostic Significance (Yes, No or Unknown)
|TSG<ref name=":3" />
!Therapeutic Significance (Yes, No or Unknown)
|Recurrent (~5%)<ref name=":2" />
!Notes
|D,P
|No
|Presence of a driver mutation associated with shorter overall survival<ref name=":2" />
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|BCOR/ BCORL1
 
|Predominantly truncating mutations <ref name=":2" />
7
|TSG<ref name=":3" />
|<span class="blue-text">EXAMPLE:</span> Loss
|Rare
|<span class="blue-text">EXAMPLE:</span>
|D,P
 
chr7:1- 159,335,973 [hg38]
|<span class="blue-text">EXAMPLE:</span>
 
chr7
|Yes
|Yes
|No
|No
|<span class="blue-text">EXAMPLE:</span>
|Presence of a driver mutation associated with shorter overall survival<ref name=":2" />  
 
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|TET2
 
|Truncating mutations<ref name=":2" />
8
|TSG<ref name=":3" />
|<span class="blue-text">EXAMPLE:</span> Gain
|Rare
|<span class="blue-text">EXAMPLE:</span>
|D,P
 
chr8:1-145,138,636 [hg38]
|<span class="blue-text">EXAMPLE:</span>
 
chr8
|No
|No
|No
|Presence of a driver mutation associated with shorter overall survival<ref name=":2" />
|No
|<span class="blue-text">EXAMPLE:</span>
 
Common recurrent secondary finding for t(8;21) (add reference).
|}
==Characteristic Chromosomal Patterns==
 
Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis. Do not delete table.'')</span>
 
{| class="wikitable sortable"
|-
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|KDM6A
 
|Truncating mutations, missense (p.P887L)<ref name=":2" />
Co-deletion of 1p and 18q
|TSG<ref name=":3" />
|Yes
|Rare
|No
|D,P
|No
|No
|<span class="blue-text">EXAMPLE:</span>
|Presence of a driver mutation associated with shorter overall survival<ref name=":2" />
 
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|}
|}
==Gene Mutations (SNV / INDEL)==


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well as either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable. Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Do not delete table.'') </span>
*
 
{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
!'''Diagnostic Significance (Yes, No or Unknown)'''
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations
 
<span class="blue-text">EXAMPLE:</span>
 
EGFR; Exon 20 mutations
 
<span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations
|<span class="blue-text">EXAMPLE:</span> TSG
|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
 
<span class="blue-text">EXAMPLE:</span> 30% (add Reference)
|<span class="blue-text">EXAMPLE:</span> IDH1 R123H
|<span class="blue-text">EXAMPLE:</span> EGFR amplification
|
|
|
|<span class="blue-text">EXAMPLE:</span>  Excludes hairy cell leukemia (HCL) (add reference).
<br />
|}
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.


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==
 
A high CPG-island methylation pattern has been described in a subtype of NK-cell CAEBV with a poor prognosis; these high methylation cases also showed higher tumor mutational burden (TMB) and frequent copy number alterations (CNAs).<ref name=":4">{{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>
Put your text here
 
==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table. Do not delete table.'')</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations
|DDX3X
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|Encodes RNA helicase
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
|Involved in cell signaling, transcriptional regulation, and viral replication. <ref>{{Cite journal|last=Bollard|first=Catherine M.|last2=Cohen|first2=Jeffrey I.|date=2018-06-28|title=How I treat T-cell chronic active Epstein-Barr virus disease|url=https://pubmed.ncbi.nlm.nih.gov/29712633|journal=Blood|volume=131|issue=26|pages=2899–2905|doi=10.1182/blood-2018-03-785931|issn=1528-0020|pmc=6024635|pmid=29712633}}</ref>
|-
Exact role in CAEBV-pathogenesis not fully elucidated.<ref name=":4" />
|<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|-
|<span class="blue-text">EXAMPLE:</span>  KMT2C and ARID1A; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span>  Histone modification, chromatin remodeling
|<span class="blue-text">EXAMPLE:</span>  Abnormal gene expression program
|}
|}
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==


Put your text here
* '''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>'''
** 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.


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


Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
* Germline mutations have only rarely been detected in CAEBV<ref>{{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>  


==Additional Information==
==Additional Information==


Put your text here
* 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)


==Links==
==Links==


[[HAEM4:EBV-Positive T-cell and NK-cell Lymphoproliferative Diseases of Childhood]]
[[HAEM4:EBV-Positive T-cell and NK-cell Lymphoproliferative Diseases of Childhood]]
Put your links here (use "Link" icon at top of page)


==References==
==References==
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />
<references />


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==Notes==
==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 CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
<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): 
 
       
<nowiki>*</nowiki>''Citation of this Page'': “Systemic chronic active EBV disease”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Systemic_chronic_active_EBV_disease</nowiki>.
<nowiki>*</nowiki>''Citation of this Page'': “Systemic chronic active EBV disease”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Systemic_chronic_active_EBV_disease</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases S]]
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases S]]
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