Bailey.Glen: Created page with "==Primary Author(s)== Lisa A. Lansdon, PhD & Linda D. Cooley, MD, MBA TOC ==Cancer Category/Type== *Mature T- and NK-cell Neoplasms ==Cancer Sub-Classification..."

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Created page with "==Primary Author(s)*== *Lisa A. Lansdon, PhD & Linda D. Cooley, MD, MBA __TOC__ ==Cancer Category/Type== *Mature T- and NK-cell Neoplasms ==Cancer Sub-Classification..."

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==Primary Author(s)*==

*Lisa A. Lansdon, PhD & Linda D. Cooley, MD, MBA

__TOC__

==Cancer Category/Type==

*[[Mature T- and NK-cell Neoplasms]]

==Cancer Sub-Classification / Subtype==

*Systemic EBV-Positive T-cell Lymphoma of Childhood

==Definition / Description of Disease<ref name=":0">{{Cite journal|last=Kimura|first=H.|last2=Hoshino|first2=Y.|last3=Kanegane|first3=H.|last4=Tsuge|first4=I.|last5=Okamura|first5=T.|last6=Kawa|first6=K.|last7=Morishima|first7=T.|date=2001-07-15|title=Clinical and virologic characteristics of chronic active Epstein-Barr virus infection|url=https://pubmed.ncbi.nlm.nih.gov/11435294|journal=Blood|volume=98|issue=2|pages=280–286|doi=10.1182/blood.v98.2.280|issn=0006-4971|pmid=11435294}}</ref><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=":2">{{Cite journal|last=Kikuta|first=H.|last2=Sakiyama|first2=Y.|last3=Matsumoto|first3=S.|last4=Oh-Ishi|first4=T.|last5=Nakano|first5=T.|last6=Nagashima|first6=T.|last7=Oka|first7=T.|last8=Hironaka|first8=T.|last9=Hirai|first9=K.|date=1993-12-01|title=Fatal Epstein-Barr virus-associated hemophagocytic syndrome|url=https://pubmed.ncbi.nlm.nih.gov/8241498|journal=Blood|volume=82|issue=11|pages=3259–3264|issn=0006-4971|pmid=8241498}}</ref><ref name=":3">{{Cite journal|last=Su|first=I. J.|last2=Chen|first2=R. L.|last3=Lin|first3=D. T.|last4=Lin|first4=K. S.|last5=Chen|first5=C. C.|date=1994-06|title=Epstein-Barr virus (EBV) infects T lymphocytes in childhood EBV-associated hemophagocytic syndrome in Taiwan|url=https://pubmed.ncbi.nlm.nih.gov/8203462|journal=The American Journal of Pathology|volume=144|issue=6|pages=1219–1225|issn=0002-9440|pmc=1887465|pmid=8203462}}</ref><ref name=":4">{{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><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>==

*A life-threatening clonal disease resulting from primary Epstein-Barr virus (EBV) infected T-cells or in the setting of systemic chronic active EBV infection (CAEBV)
*T-lymphocytes infected with EBV infiltrate the liver, spleen, lungs, skin and marrow, resulting in multiorgan failure, sepsis and death
*Rapidly progressive
*Most common in children and young adults after a primary EBV infection; can occur in adult patients

==Synonyms / Terminology<ref name=":1" /><ref name=":5" /><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>==

*Fulminant EBV-positive T-cell lymphoproliferative disorder of childhood
*Sporadic fatal infectious mononucleosis
*Fulminant hemophagocytic syndrome in children in Taiwan
*Fatal EBV-associated hemophagocytic syndrome
*Severe Chronic Active EBV Infection (CAEBV; legacy term)

==Epidemiology / Prevalence<ref name=":0" /><ref name=":1" /><ref name=":2" /><ref name=":3" /><ref name=":4" /><ref>{{Cite journal|last=Kimura|first=Hiroshi|last2=Morishima|first2=Tsuneo|last3=Kanegane|first3=Hirokazu|last4=Ohga|first4=Shouichi|last5=Hoshino|first5=Yo|last6=Maeda|first6=Akihiko|last7=Imai|first7=Shosuke|last8=Okano|first8=Motohiko|last9=Morio|first9=Tomohiro|date=2003-02-15|title=Prognostic factors for chronic active Epstein-Barr virus infection|url=https://pubmed.ncbi.nlm.nih.gov/12599068|journal=The Journal of Infectious Diseases|volume=187|issue=4|pages=527–533|doi=10.1086/367988|issn=0022-1899|pmid=12599068}}</ref>==

*Most prevalent in Asia (Japan and Taiwan)
*Has been reported in Mexico, Central and South America
*Rare in Western countries
*Children and young adults
*No sex predilection

==Clinical Features==

Signs & Symptoms <ref name=":0" /><ref name=":1" /><ref name=":2" /><ref name=":3" /><ref name=":4" /><ref name=":6">{{Cite journal|last=Jones|first=J. F.|last2=Shurin|first2=S.|last3=Abramowsky|first3=C.|last4=Tubbs|first4=R. R.|last5=Sciotto|first5=C. G.|last6=Wahl|first6=R.|last7=Sands|first7=J.|last8=Gottman|first8=D.|last9=Katz|first9=B. Z.|date=1988-03-24|title=T-cell lymphomas containing Epstein-Barr viral DNA in patients with chronic Epstein-Barr virus infections|url=https://pubmed.ncbi.nlm.nih.gov/2831453|journal=The New England Journal of Medicine|volume=318|issue=12|pages=733–741|doi=10.1056/NEJM198803243181203|issn=0028-4793|pmid=2831453}}</ref><ref name=":7">{{Cite journal|last=Kanegane|first=H.|last2=Bhatia|first2=K.|last3=Gutierrez|first3=M.|last4=Kaneda|first4=H.|last5=Wada|first5=T.|last6=Yachie|first6=A.|last7=Seki|first7=H.|last8=Arai|first8=T.|last9=Kagimoto|first9=S.|date=1998-03-15|title=A syndrome of peripheral blood T-cell infection with Epstein-Barr virus (EBV) followed by EBV-positive T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/9490694|journal=Blood|volume=91|issue=6|pages=2085–2091|issn=0006-4971|pmid=9490694}}</ref>

*Acute onset fever that is unresponsive to antibiotics
*General malaise
*Splenic and liver enlargement
*Liver failure/jaundice
*Lymphadenopathy (uncommon)

Laboratory Findings <ref name=":1" /><ref name=":4" />

*Pancytopenia
*Abnormal liver function tests
*Abnormal EBV serology with low or absent anti-VCA IgM antibodies
*Hemophagocytic syndrome (coagulopathy, multiorgan failure and sepsis)
*CAEBV infection (in some cases)

==Sites of Involvement<ref name=":5" />==
Systemic disease with most commonly involved sites:

*Liver
*Spleen
*Lymph nodes
*Bone marrow
*Skin
*Lung

==Morphologic Features<ref name=":1" /><ref name=":4" />==

*Small T-cells
*Medium to large lymphoid cells with irregular nuclei and frequent mitoses (less common)
*Sinusoidal infiltration of liver and spleen with hemophagocytosis
*Spleen: depleted white pulp
*Liver: prominent portal and sinusoidal infiltration, cholestasis, steatosis and necrosis
*Lymph nodes: preserved architecture, sinus histiocytosis and erythrophagocytosis
*Bone marrow: histiocytic hyperplasia and erythrophagocytosis

==Immunophenotype<ref name=":1" /><ref name=":3" /><ref name=":5" /><ref name=":6" /><ref name=":7" /><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>==

<br />

{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive||CD2, CD3, TIA1, CD8 (''de novo'' EBV infection), CD4 (severe CAEBV)
|-
|Negative||CD56
|}

==Chromosomal Rearrangements (Gene Fusions)==

*No reported gene fusions

==Characteristic Chromosomal Aberrations / Patterns<ref name=":0" /><ref name=":1" /><ref name=":2" /><ref name=":4" /><ref name=":5" /><ref name=":8" /><ref>{{Cite journal|last=Au|first=W.-Y.|last2=Ma|first2=S.-Y.|last3=Chim|first3=C.-S.|last4=Choy|first4=C.|last5=Loong|first5=F.|last6=Lie|first6=A. K. W.|last7=Lam|first7=C. C. K.|last8=Leung|first8=A. Y. H.|last9=Tse|first9=E.|date=2005-02|title=Clinicopathologic features and treatment outcome of mature T-cell and natural killer-cell lymphomas diagnosed according to the World Health Organization classification scheme: a single center experience of 10 years|url=https://pubmed.ncbi.nlm.nih.gov/15668271|journal=Annals of Oncology: Official Journal of the European Society for Medical Oncology|volume=16|issue=2|pages=206–214|doi=10.1093/annonc/mdi037|issn=0923-7534|pmid=15668271}}</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>==

*Monoclonal T-cell receptor gene rearrangements
*Aneuploidies and chromosomal gains/losses have been observed but no observable patterns to-date; Associated with worse prognosis

==Genomic Gain/Loss/LOH==

*N/A

==Gene Mutations (SNV/INDEL)<ref name=":1" /><ref name=":4" /><ref name=":8" />==

*All cases analyzed carry type A EBV with the wildtype or 30 bp deleted product of ''LMP1''

==Epigenomics (Methylation)==

*N/A

==Genes and Main Pathways Involved==

*N/A

==Diagnostic Testing Methods==

*Morphology and immunophenotyping (IHC or flow cytometry)
*Clonal proliferation of T cells (polyclonal cases have been reported<ref>{{Cite journal|last=Chen|first=Guoshu|last2=Chen|first2=Li|last3=Qin|first3=Xiaohua|last4=Huang|first4=Zhuoya|last5=Xie|first5=Xiaoling|last6=Li|first6=Guowei|last7=Xu|first7=Bing|date=2014|title=Systemic Epstein-Barr virus positive T-cell lymphoproliferative disease of childhood with hemophagocytic syndrome|url=https://pubmed.ncbi.nlm.nih.gov/25400806|journal=International Journal of Clinical and Experimental Pathology|volume=7|issue=10|pages=7110–7113|issn=1936-2625|pmc=4230111|pmid=25400806}}</ref>)

==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==

*N/A

==Familial Forms==

*Racial predisposition suggests a genetic background; however, no specific genetic abnormalities have been detected

==Other Information==

Differential Diagnosis<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><ref>{{Cite journal|last=Cohen|first=Jeffrey I.|last2=Iwatsuki|first2=Keiji|last3=Ko|first3=Young-Hyeh|last4=Kimura|first4=Hiroshi|last5=Manoli|first5=Irini|last6=Ohshima|first6=Koichi|last7=Pittaluga|first7=Stefania|last8=Quintanilla-Martinez|first8=Leticia|last9=Jaffe|first9=Elaine S.|date=04 2020|title=Epstein-Barr virus NK and T cell lymphoproliferative disease: report of a 2018 international meeting|url=https://pubmed.ncbi.nlm.nih.gov/31833428|journal=Leukemia & Lymphoma|volume=61|issue=4|pages=808–819|doi=10.1080/10428194.2019.1699080|issn=1029-2403|pmid=31833428}}</ref>

*Clinical and pathologic features of EBV-HLH and systemic EBV positive T-cell lymphoma of childhood overlap. These entities have been suggested to represent a biologic continuum
*EBV-HLH is defined by a constellation of clinical symptoms and laboratory changes that might be triggered by EBV-associated lymphomas including aggressive NK-cell leukemia (ANKL) and systemic EBV-positive T-cell lymphoma of childhood
*EBV-HLH associated with genetic abnormalities (primary HLH) can be excluded by genetic analysis and family history
*Systemic CAEBV infection is difficult to differentiate from systemic EBV-positive T-cell lymphoma based only on morphologic grounds. The clinical information is necessary to achieve the correct diagnosis
*ANKL is very similar to systemic EBV-positive T-cell lymphoma but the tumor cells express NK cell markers (CD56+) and do not show monoclonal TCR gene rearrangements

Additional Information<ref name=":9" /><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><ref>{{Cite journal|last=Yoshida|first=Masanori|last2=Osumi|first2=Tomoo|last3=Imadome|first3=Ken-Ichi|last4=Tomizawa|first4=Daisuke|last5=Kato|first5=Motohiro|last6=Miyazawa|first6=Noritaka|last7=Ito|first7=Reiko|last8=Nakazawa|first8=Atsuko|last9=Matsumoto|first9=Kimikazu|date=03 2018|title=Successful treatment of systemic EBV positive T-cell lymphoma of childhood using the SMILE regimen|url=https://pubmed.ncbi.nlm.nih.gov/29648917|journal=Pediatric Hematology and Oncology|volume=35|issue=2|pages=121–124|doi=10.1080/08880018.2018.1459982|issn=1521-0669|pmid=29648917}}</ref>

*Poor outcomes overall due to cytokine storm in HLH
*Survival rates lower with disease onset after 8 years and with liver dysfunction at diagnosis
*Death due to rapid disease progression for which there is no effective treatment
*No known treatment; some case reports of response to etoposide and dexamethasone-based regimen followed by allogenic hematopoietic stem cell transplantation

==Links==

[[EBV-Positive T-cell and NK-cell Lymphoproliferative Diseases of Childhood]]

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==References==
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===EXAMPLE Book===

#Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p129-171.

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HAEM4Backup:Systemic EBV-Positive T-cell Lymphoma of Childhood - Revision history

Bailey.Glen: Created page with "==Primary Author(s)*== *Lisa A. Lansdon, PhD & Linda D. Cooley, MD, MBA __TOC__ ==Cancer Category/Type== *Mature T- and NK-cell Neoplasms ==Cancer Sub-Classification..."

Bailey.Glen: Created page with "==Primary Author(s)== Lisa A. Lansdon, PhD & Linda D. Cooley, MD, MBA TOC ==Cancer Category/Type== *Mature T- and NK-cell Neoplasms ==Cancer Sub-Classification..."