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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.)]] |
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| {{Under Construction}}
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| <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]].
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| <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>
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| ==Primary Author(s)*== | | ==Primary Author(s)*== |
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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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| ==Individual Region Genomic Gain/Loss/LOH== | | ==Individual Region Genomic Gain/Loss/LOH== |
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| * Cytogenetic abnormalities found in 30-35% of cases of SEBVTCL of childhood. The WHO 5th edition and International Consensus Classification note that cytogenetic abnormalities favor a diagnosis of SEBVTCL over EBV-positive nonfamilial HLH.<ref>Arber DA, Borowitz MJ, Cook JR, et al. ''The International Consensus Classification of Myeloid and Lymphoid Neoplasms''.; 2025.</ref> <ref name=":3" /><ref name=":6" /><ref name=":10" /> | | * Cytogenetic abnormalities found in 30-35% of cases of SEBVTCL of childhood. The WHO 5th edition and International Consensus Classification note that cytogenetic abnormalities favor a diagnosis of SEBVTCL over EBV-positive nonfamilial HLH.<ref name=":0">Arber DA, Borowitz MJ, Cook JR, et al. ''The International Consensus Classification of Myeloid and Lymphoid Neoplasms''.; 2025.</ref> <ref name=":3" /><ref name=":6" /><ref name=":10" /> |
| * Aneuploidies and chromosomal gains/losses have been observed but no observable patterns to-date; Associated with worse prognosis<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" /><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=":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><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=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><ref name=":7" /> | | * No observable patterns in the cytogenetic/karyotypic abnormalities to-date; cytogenetic abnormalities associated with worse prognosis<ref name=":7" /><ref name=":5">{{Cite journal|last=Hue|first=Susan Swee-Shan|last2=Oon|first2=Ming Liang|last3=Wang|first3=Shi|last4=Tan|first4=Soo-Yong|last5=Ng|first5=Siok-Bian|date=2020-01|title=Epstein-Barr virus-associated T- and NK-cell lymphoproliferative diseases: an update and diagnostic approach|url=https://pubmed.ncbi.nlm.nih.gov/31767131|journal=Pathology|volume=52|issue=1|pages=111–127|doi=10.1016/j.pathol.2019.09.011|issn=1465-3931|pmid=31767131}}</ref><ref name=":9">{{Cite journal|last=Smith|first=Megan C.|last2=Cohen|first2=Daniel N.|last3=Greig|first3=Bruce|last4=Yenamandra|first4=Ashwini|last5=Vnencak-Jones|first5=Cindy|last6=Thompson|first6=Mary Ann|last7=Kim|first7=Annette S.|date=2014|title=The ambiguous boundary between EBV-related hemophagocytic lymphohistiocytosis and systemic EBV-driven T cell lymphoproliferative disorder|url=https://pubmed.ncbi.nlm.nih.gov/25337215|journal=International Journal of Clinical and Experimental Pathology|volume=7|issue=9|pages=5738–5749|issn=1936-2625|pmc=4203186|pmid=25337215}}</ref><ref>{{Cite journal|last=Chen|first=J. S.|last2=Tzeng|first2=C. C.|last3=Tsao|first3=C. J.|last4=Su|first4=W. C.|last5=Chen|first5=T. Y.|last6=Jung|first6=Y. C.|last7=Su|first7=I. J.|date=1997-09|title=Clonal karyotype abnormalities in EBV-associated hemophagocytic syndrome|url=https://pubmed.ncbi.nlm.nih.gov/9407723|journal=Haematologica|volume=82|issue=5|pages=572–576|issn=0390-6078|pmid=9407723}}</ref> |
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| ==Characteristic Chromosomal or Other Global Mutational Patterns== | | ==Characteristic Chromosomal or Other Global Mutational Patterns== |
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| Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as 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; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
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| |<span class="blue-text">EXAMPLE:</span> | | |N/A |
| Co-deletion of 1p and 18q
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| |<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
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| |<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
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| |<span class="blue-text">EXAMPLE:</span> D, P
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| Microsatellite instability - hypermutated
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| |<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
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| <blockquote class="blockedit">{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote>
| | == Gene Mutations (SNV/INDELS) == |
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| *<blockquote class="blockedit">
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| <center><span style="color:Maroon">'''End of V4 Section'''</span>
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| <center><span style="color:Maroon">'''End of V4 Section'''</span>
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| </blockquote>
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| ==Gene Mutations (SNV/INDEL)== | |
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| * Somatic mutations have been reported; however, consistent/recurrent mutations are not well-described.<ref name=":10" />
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| ** Rare reports of mutations in FYN<ref name=":10" />,
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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> |
| | ** ''FYN'' mutations have been reported in two cases <ref name=":10" /><ref name=":2" /> |
| | ** Mutations in ''KMT2D'', ''MFHAS1'', ''STAT3'', ''EP300'', ''ITPKB'', ''DDX3X'', ''NOTCH1'', ''NOTCH2'', and ''TET2'' (amongst others) have also been reported<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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| |<span class="blue-text">EXAMPLE:</span>''EGFR'' | | |N/A |
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| |<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
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| |<span class="blue-text">EXAMPLE:</span> Oncogene
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| |<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
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| |<span class="blue-text">EXAMPLE:</span> T
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| |<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
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| |<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
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| |<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
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| |<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
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| |<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
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| |<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
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| |<span class="blue-text">EXAMPLE:</span> P
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| |<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
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| |<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
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| |<span class="blue-text">EXAMPLE:</span> Activating mutations
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| |<span class="blue-text">EXAMPLE:</span> Oncogene
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| |<span class="blue-text">EXAMPLE:</span> Common (melanoma)
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| |}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. | | |}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content. |
| ==Epigenomic Alterations== | | |
| | == Epigenomic Alterations == |
| N/A | | N/A |
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| ==Genes and Main Pathways Involved== | | == Genes and Main Pathways Involved == |
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| ==Genetic Diagnostic Testing Methods==
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| *WHO 5th edition ''essential'' diagnostic criteria include:<ref name=":3" /><ref name=":6" />
| | == Genetic Diagnostic Testing Methods == |
| **Acute presentation with fever and systemic symptoms
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| **Multiorgan infiltration by atypical T-cells
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| **EBV-positivity exclusion of known immunodeficiency
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| *WHO 5th edition ''desirable'' diagnostic criteria include:<ref name=":3" /><ref name=":6" />
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| **Clonal TCR-gene rearrangement
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| **Hemophagocytic lymphohistiocytosis (HLH)
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| **Hepatosplenomegaly
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| *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" />
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| ==Familial Forms==
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| *Racial predisposition suggests a genetic background; however, no specific genetic abnormalities have been detected
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| ==Additional Information==
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| * Typically occurs following primary acute EBV infection; though, it rarely reported in patients with a history of systemic chronic active EBV (CAEBV)<ref name=":10" />
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| | * 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" /> |
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| | * Differential Diagnosis with EBV-positive HLH is challenging |
| | ** TCR-gene rearrangements and aberrant T-cell phenotypes can be seen in both SEBVTCL of childhood and EBV-positive HLH |
| | ** The WHO 5th edition and International Consensus Classification note that cytogenetic abnormalities favor a diagnosis of SEBVTCL over EBV-positive nonfamilial HLH.<ref name=":3" /><ref name=":0" /> |
| | ** Primary/familial EBV-positive HLH can be excluded by family history and genetic analysis<ref name=":10" /> |
| | * TCR-gene rearrangements can be detected via PCR or NGS methods. Cytogenetic abnormalities can be detected with karyotype and chromosome microarray (CMA). |
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| | == Familial Forms == |
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| | N/A |
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| All cases analyzed carry type A EBV with the wildtype or 30 bp deleted product of ''LMP1''<ref name=":1" /><ref name=":4" /><ref name=":8" />
| | == Additional Information == |
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| 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>
| | * 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" /> |
| | * 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> |
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| *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
| | == Links == |
| *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
| | [[HAEM4:EBV-Positive T-cell and NK-cell Lymphoproliferative Diseases of Childhood]]<center><center> |
| *EBV-HLH associated with genetic abnormalities (primary HLH) can be excluded by genetic analysis and family history
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| *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
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| *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
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| 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>
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| *Poor outcomes overall due to cytokine storm in HLH
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| *Survival rates lower with disease onset after 8 years and with liver dysfunction at diagnosis
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| *Death due to rapid disease progression for which there is no effective treatment
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| *No known treatment; some case reports of response to etoposide and dexamethasone-based regimen followed by allogenic hematopoietic stem cell transplantation
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| ==Links==
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| [[HAEM4:EBV-Positive T-cell and NK-cell Lymphoproliferative Diseases of Childhood]]
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| ==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 where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. 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. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references />
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