Compendium of Cancer Genome Aberrations

HAEM5:Extranodal NK/T-cell lymphoma: Difference between revisions

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==Definition / Description of Disease==
==Definition / Description of Disease==


*Lymphoma of NK or T-cell lineage strongly associated with Epstein-Barr virus<ref name=":6">{{Cite journal|last=Jaffe|first=E. S.|last2=Krenacs|first2=L.|last3=Kumar|first3=S.|last4=Kingma|first4=D. W.|last5=Raffeld|first5=M.|date=1999-01|title=Extranodal peripheral T-cell and NK-cell neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/9894469|journal=American Journal of Clinical Pathology|volume=111|issue=1 Suppl 1|pages=S46–55|issn=0002-9173|pmid=9894469}}</ref>. The lineage (NK or T-cell) has no clinical significance<ref>{{Cite journal|last=Wang|first=Hua|last2=Fu|first2=Bi-Bo|last3=Gale|first3=Robert Peter|last4=Liang|first4=Yang|date=2021-09|title=NK-/T-cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/34117356|journal=Leukemia|volume=35|issue=9|pages=2460–2468|doi=10.1038/s41375-021-01313-2|issn=1476-5551|pmc=8410593|pmid=34117356}}</ref>.
*Lymphoma of NK or T-cell lineage strongly associated with Epstein-Barr virus<ref name=":6">{{Cite journal|last=Jaffe|first=E. S.|last2=Krenacs|first2=L.|last3=Kumar|first3=S.|last4=Kingma|first4=D. W.|last5=Raffeld|first5=M.|date=1999-01|title=Extranodal peripheral T-cell and NK-cell neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/9894469|journal=American Journal of Clinical Pathology|volume=111|issue=1 Suppl 1|pages=S46–55|issn=0002-9173|pmid=9894469}}</ref>. The lineage (NK or T-cell) has no clinical significance<ref name=":16">{{Cite journal|last=Wang|first=Hua|last2=Fu|first2=Bi-Bo|last3=Gale|first3=Robert Peter|last4=Liang|first4=Yang|date=2021-09|title=NK-/T-cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/34117356|journal=Leukemia|volume=35|issue=9|pages=2460–2468|doi=10.1038/s41375-021-01313-2|issn=1476-5551|pmc=8410593|pmid=34117356}}</ref>.
*Divided into nasal and non-nasal types, the latter most often occurring in the skin and intestinal tract<ref name=":5">Chan J. K. C., et al., (2017). Extranodal NK/T-cell lymphoma, nasal type, 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. Revised 4th Edition. IARC Press: Lyon, France, p.368-371.</ref><ref name=":6" />.
*Divided into nasal and non-nasal types, the latter most often occurring in the skin and intestinal tract<ref name=":5">Chan J. K. C., et al., (2017). Extranodal NK/T-cell lymphoma, nasal type, 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. Revised 4th Edition. IARC Press: Lyon, France, p.368-371.</ref><ref name=":6" />.
*It is a destructive angiocentric disease characterized by vascular destruction and necrosis<ref>{{Cite journal|last=Aviles|first=A.|last2=Rodriguez|first2=L.|last3=Guzman|first3=R.|last4=Talavera|first4=A.|last5=Garcia|first5=E. L.|last6=Diaz-Maqueo|first6=J. C.|date=1992|title=Angiocentric T-cell lymphoma of the nose, paranasal sinuses and hard palate|url=https://pubmed.ncbi.nlm.nih.gov/1398510|journal=Hematological Oncology|volume=10|issue=3-4|pages=141–147|doi=10.1002/hon.2900100303|issn=0278-0232|pmid=1398510}}</ref>.
*It is a destructive angiocentric disease characterized by vascular destruction and necrosis<ref name=":17">{{Cite journal|last=Aviles|first=A.|last2=Rodriguez|first2=L.|last3=Guzman|first3=R.|last4=Talavera|first4=A.|last5=Garcia|first5=E. L.|last6=Diaz-Maqueo|first6=J. C.|date=1992|title=Angiocentric T-cell lymphoma of the nose, paranasal sinuses and hard palate|url=https://pubmed.ncbi.nlm.nih.gov/1398510|journal=Hematological Oncology|volume=10|issue=3-4|pages=141–147|doi=10.1002/hon.2900100303|issn=0278-0232|pmid=1398510}}</ref>.


*Differential diagnosis: sinonasal carcinomas and other lymphomas of the nasal cavity, such as diffuse large B-cell lymphoma<ref>{{Cite journal|last=Steele|first=Toby O.|last2=Buniel|first2=Maria C.|last3=Mace|first3=Jess C.|last4=El Rassi|first4=Edward|last5=Smith|first5=Timothy L.|date=2016-09|title=Lymphoma of the nasal cavity and paranasal sinuses: A case series|url=https://pubmed.ncbi.nlm.nih.gov/27657899|journal=American Journal of Rhinology & Allergy|volume=30|issue=5|pages=335–339|doi=10.2500/ajra.2016.30.4347|issn=1945-8932|pmid=27657899}}</ref>.
*Differential diagnosis: sinonasal carcinomas and other lymphomas of the nasal cavity, such as diffuse large B-cell lymphoma<ref name=":18">{{Cite journal|last=Steele|first=Toby O.|last2=Buniel|first2=Maria C.|last3=Mace|first3=Jess C.|last4=El Rassi|first4=Edward|last5=Smith|first5=Timothy L.|date=2016-09|title=Lymphoma of the nasal cavity and paranasal sinuses: A case series|url=https://pubmed.ncbi.nlm.nih.gov/27657899|journal=American Journal of Rhinology & Allergy|volume=30|issue=5|pages=335–339|doi=10.2500/ajra.2016.30.4347|issn=1945-8932|pmid=27657899}}</ref>.


==Synonyms / Terminology==
==Synonyms / Terminology==
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*Most prevalent in East Asia and Latin America.
*Most prevalent in East Asia and Latin America.
*Represents less than 1% of non-Hodgkin lymphomas in the United States
*Represents less than 1% of non-Hodgkin lymphomas in the United States
**Highest incidence among Asian Pacific Islanders and Hispanic populations<ref>{{Cite journal|last=Haverkos|first=Bradley M.|last2=Pan|first2=Zenggang|last3=Gru|first3=Alejandro A.|last4=Freud|first4=Aharon G.|last5=Rabinovitch|first5=Rachel|last6=Xu-Welliver|first6=Meng|last7=Otto|first7=Brad|last8=Barrionuevo|first8=Carlos|last9=Baiocchi|first9=Robert A.|date=2016-12|title=Extranodal NK/T-cell lymphoma, nasal type (ENKTL-NT): An update on epidemiology, clinical presentation, and natural history in North American and European cases|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5199232/|journal=Current hematologic malignancy reports|volume=11|issue=6|pages=514–527|doi=10.1007/s11899-016-0355-9|issn=1558-8211|pmc=5199232|pmid=27778143}}</ref>.
**Highest incidence among Asian Pacific Islanders and Hispanic populations<ref name=":19">{{Cite journal|last=Haverkos|first=Bradley M.|last2=Pan|first2=Zenggang|last3=Gru|first3=Alejandro A.|last4=Freud|first4=Aharon G.|last5=Rabinovitch|first5=Rachel|last6=Xu-Welliver|first6=Meng|last7=Otto|first7=Brad|last8=Barrionuevo|first8=Carlos|last9=Baiocchi|first9=Robert A.|date=2016-12|title=Extranodal NK/T-cell lymphoma, nasal type (ENKTL-NT): An update on epidemiology, clinical presentation, and natural history in North American and European cases|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5199232/|journal=Current hematologic malignancy reports|volume=11|issue=6|pages=514–527|doi=10.1007/s11899-016-0355-9|issn=1558-8211|pmc=5199232|pmid=27778143}}</ref>.


==Clinical Features==
==Clinical Features==
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Abdominal pain, GI bleeding, bowel perforation<ref name=":0">Thida AM, Gohari P. Extranodal NK-Cell Lymphoma. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: <nowiki>https://www.ncbi.nlm.nih.gov/books/NBK559207/</nowiki></ref>
Abdominal pain, GI bleeding, bowel perforation<ref name=":0">Thida AM, Gohari P. Extranodal NK-Cell Lymphoma. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: <nowiki>https://www.ncbi.nlm.nih.gov/books/NBK559207/</nowiki></ref>


B symptoms (fever, weight loss, night sweats) associated with higher clinical stage<ref>{{Cite journal|last=Takahara|first=Miki|last2=Kumai|first2=Takumi|last3=Kishibe|first3=Kan|last4=Nagato|first4=Toshihiro|last5=Harabuchi|first5=Yasuaki|date=2021-06-25|title=Extranodal NK/T-Cell Lymphoma, Nasal Type: Genetic, Biologic, and Clinical Aspects with a Central Focus on Epstein-Barr Virus Relation|url=https://pubmed.ncbi.nlm.nih.gov/34202088|journal=Microorganisms|volume=9|issue=7|pages=1381|doi=10.3390/microorganisms9071381|issn=2076-2607|pmc=8304202|pmid=34202088}}</ref>
B symptoms (fever, weight loss, night sweats) associated with higher clinical stage<ref name=":20">{{Cite journal|last=Takahara|first=Miki|last2=Kumai|first2=Takumi|last3=Kishibe|first3=Kan|last4=Nagato|first4=Toshihiro|last5=Harabuchi|first5=Yasuaki|date=2021-06-25|title=Extranodal NK/T-Cell Lymphoma, Nasal Type: Genetic, Biologic, and Clinical Aspects with a Central Focus on Epstein-Barr Virus Relation|url=https://pubmed.ncbi.nlm.nih.gov/34202088|journal=Microorganisms|volume=9|issue=7|pages=1381|doi=10.3390/microorganisms9071381|issn=2076-2607|pmc=8304202|pmid=34202088}}</ref>
|-
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|'''Laboratory Findings'''
|'''Laboratory Findings'''
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*Most are nasal type involving the upper aerodigestive tract
*Most are nasal type involving the upper aerodigestive tract
*Extranasal type may involve skin, testis, and gastrointestinal tract<ref name=":0" />.
*Extranasal type may involve skin, testis, and gastrointestinal tract<ref name=":0" />.
*Bone marrow involvement is uncommon<ref>{{Cite journal|last=Wong|first=K. F.|last2=Chan|first2=J. K.|last3=Cheung|first3=M. M.|last4=So|first4=J. C.|date=2001-02|title=Bone marrow involvement by nasal NK cell lymphoma at diagnosis is uncommon|url=https://pubmed.ncbi.nlm.nih.gov/11211616|journal=American Journal of Clinical Pathology|volume=115|issue=2|pages=266–270|doi=10.1309/E5PR-6A9R-Q02N-8QVW|issn=0002-9173|pmid=11211616}}</ref>.
*Bone marrow involvement is uncommon<ref name=":21">{{Cite journal|last=Wong|first=K. F.|last2=Chan|first2=J. K.|last3=Cheung|first3=M. M.|last4=So|first4=J. C.|date=2001-02|title=Bone marrow involvement by nasal NK cell lymphoma at diagnosis is uncommon|url=https://pubmed.ncbi.nlm.nih.gov/11211616|journal=American Journal of Clinical Pathology|volume=115|issue=2|pages=266–270|doi=10.1309/E5PR-6A9R-Q02N-8QVW|issn=0002-9173|pmid=11211616}}</ref>.


==Morphologic Features==
==Morphologic Features==
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Pitfalls:
Pitfalls:


*Mucosal ulceration and superimposed inflammation can mimic an inflammatory process, particularly in less aggressive cases<ref>Devins, K., Schuster, S.J., Caponetti, G.C. ''et al.'' Rare case of low-grade extranodal NK/T-cell lymphoma, nasal type, arising in the setting of chronic rhinosinusitis and harboring a novel N-terminal ''KIT'' mutation. ''Diagn Pathol'' 13, 92 (2018). <nowiki>https://doi.org/10.1186/s13000-018-0765-1</nowiki></ref>.
*Mucosal ulceration and superimposed inflammation can mimic an inflammatory process, particularly in less aggressive cases<ref name=":22">Devins, K., Schuster, S.J., Caponetti, G.C. ''et al.'' Rare case of low-grade extranodal NK/T-cell lymphoma, nasal type, arising in the setting of chronic rhinosinusitis and harboring a novel N-terminal ''KIT'' mutation. ''Diagn Pathol'' 13, 92 (2018). <nowiki>https://doi.org/10.1186/s13000-018-0765-1</nowiki></ref>.
*Pseudoepitheliomatous hyperplasia of the overlying mucosal epithelium can mimic squamous cell carcinoma<ref>{{Cite journal|last=Ling|first=Yi-Hong|last2=Zhu|first2=Chong-Mei|last3=Wen|first3=Shi-Hong|last4=Luo|first4=Rong-Zhen|last5=Li|first5=Peng|last6=Cao|first6=Yun|last7=Rao|first7=Hui-Lan|last8=Lin|first8=Su-Xia|last9=Cai|first9=Mu-Yan|date=2015-09|title=Pseudoepitheliomatous hyperplasia mimicking invasive squamous cell carcinoma in extranodal natural killer/T-cell lymphoma: a report of 34 cases|url=https://pubmed.ncbi.nlm.nih.gov/25619876|journal=Histopathology|volume=67|issue=3|pages=404–409|doi=10.1111/his.12656|issn=1365-2559|pmid=25619876}}</ref><ref>{{Cite journal|last=Xiang|first=Chun-Xiang|last2=Chen|first2=Zi-Hang|last3=Zhao|first3=Sha|last4=Gao|first4=Li-Min|last5=Tao|first5=Qing|last6=Zuo|first6=Zhuo|last7=Liu|first7=Xiao-Yu|last8=Liu|first8=Wei-Ping|date=2019-07|title=Laryngeal Extranodal Nasal-type Natural Killer/T-cell Lymphoma: A Clinicopathologic Study of 31 Cases in China|url=https://pubmed.ncbi.nlm.nih.gov/31045893|journal=The American Journal of Surgical Pathology|volume=43|issue=7|pages=995–1004|doi=10.1097/PAS.0000000000001266|issn=1532-0979|pmid=31045893}}</ref>.
*Pseudoepitheliomatous hyperplasia of the overlying mucosal epithelium can mimic squamous cell carcinoma<ref name=":23">{{Cite journal|last=Ling|first=Yi-Hong|last2=Zhu|first2=Chong-Mei|last3=Wen|first3=Shi-Hong|last4=Luo|first4=Rong-Zhen|last5=Li|first5=Peng|last6=Cao|first6=Yun|last7=Rao|first7=Hui-Lan|last8=Lin|first8=Su-Xia|last9=Cai|first9=Mu-Yan|date=2015-09|title=Pseudoepitheliomatous hyperplasia mimicking invasive squamous cell carcinoma in extranodal natural killer/T-cell lymphoma: a report of 34 cases|url=https://pubmed.ncbi.nlm.nih.gov/25619876|journal=Histopathology|volume=67|issue=3|pages=404–409|doi=10.1111/his.12656|issn=1365-2559|pmid=25619876}}</ref><ref name=":24">{{Cite journal|last=Xiang|first=Chun-Xiang|last2=Chen|first2=Zi-Hang|last3=Zhao|first3=Sha|last4=Gao|first4=Li-Min|last5=Tao|first5=Qing|last6=Zuo|first6=Zhuo|last7=Liu|first7=Xiao-Yu|last8=Liu|first8=Wei-Ping|date=2019-07|title=Laryngeal Extranodal Nasal-type Natural Killer/T-cell Lymphoma: A Clinicopathologic Study of 31 Cases in China|url=https://pubmed.ncbi.nlm.nih.gov/31045893|journal=The American Journal of Surgical Pathology|volume=43|issue=7|pages=995–1004|doi=10.1097/PAS.0000000000001266|issn=1532-0979|pmid=31045893}}</ref>.


==Immunophenotype==
==Immunophenotype==
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|cytoplasmic CD3ε, CD2, CD56, granzyme B, and TIA-1
|cytoplasmic CD3ε, CD2, CD56, granzyme B, and TIA-1
|-
|-
|Positive (subset)||TCR αβ/γδ, HLA-DR, CD25, pSTAT3, CXCL13, IRF4/MUM1, CD16, Fas, FasL, MATK, CD30<ref>{{Cite journal|last=Li|first=Shaoying|last2=Feng|first2=Xiaoli|last3=Li|first3=Ting|last4=Zhang|first4=Shuang|last5=Zuo|first5=Zhuang|last6=Lin|first6=Pei|last7=Konoplev|first7=Sergej|last8=Bueso-Ramos|first8=Carlos E.|last9=Vega|first9=Francisco|date=2013-01|title=Extranodal NK/T-cell lymphoma, nasal type: a report of 73 cases at MD Anderson Cancer Center|url=https://pubmed.ncbi.nlm.nih.gov/23232851|journal=The American Journal of Surgical Pathology|volume=37|issue=1|pages=14–23|doi=10.1097/PAS.0b013e31826731b5|issn=1532-0979|pmid=23232851}}</ref><ref>{{Cite journal|last=Jhuang|first=Jie-Yang|last2=Chang|first2=Sheng-Tsung|last3=Weng|first3=Shih-Feng|last4=Pan|first4=Shien-Tung|last5=Chu|first5=Pei-Yi|last6=Hsieh|first6=Pin-Pen|last7=Wei|first7=Chih-Hsin|last8=Chou|first8=Shih-Cheng|last9=Koo|first9=Chiew-Loon|date=2015-02|title=Extranodal natural killer/T-cell lymphoma, nasal type in Taiwan: a relatively higher frequency of T-cell lineage and poor survival for extranasal tumors|url=https://pubmed.ncbi.nlm.nih.gov/25554090|journal=Human Pathology|volume=46|issue=2|pages=313–321|doi=10.1016/j.humpath.2014.11.008|issn=1532-8392|pmid=25554090}}</ref><ref>{{Cite journal|last=Pongpruttipan|first=Tawatchai|last2=Sukpanichnant|first2=Sanya|last3=Assanasen|first3=Thamathorn|last4=Wannakrairot|first4=Pongsak|last5=Boonsakan|first5=Paisarn|last6=Kanoksil|first6=Wasana|last7=Kayasut|first7=Kanita|last8=Mitarnun|first8=Winyou|last9=Khuhapinant|first9=Archrob|date=2012-04|title=Extranodal NK/T-cell lymphoma, nasal type, includes cases of natural killer cell and αβ, γδ, and αβ/γδ T-cell origin: a comprehensive clinicopathologic and phenotypic study|url=https://pubmed.ncbi.nlm.nih.gov/22314189|journal=The American Journal of Surgical Pathology|volume=36|issue=4|pages=481–499|doi=10.1097/PAS.0b013e31824433d8|issn=1532-0979|pmid=22314189}}</ref><ref>{{Cite journal|last=Jaffe|first=E. S.|last2=Chan|first2=J. K.|last3=Su|first3=I. J.|last4=Frizzera|first4=G.|last5=Mori|first5=S.|last6=Feller|first6=A. C.|last7=Ho|first7=F. C.|date=1996-01|title=Report of the Workshop on Nasal and Related Extranodal Angiocentric T/Natural Killer Cell Lymphomas. Definitions, differential diagnosis, and epidemiology|url=https://pubmed.ncbi.nlm.nih.gov/8540601|journal=The American Journal of Surgical Pathology|volume=20|issue=1|pages=103–111|doi=10.1097/00000478-199601000-00012|issn=0147-5185|pmid=8540601}}</ref><ref>{{Cite journal|last=Ohshima|first=K.|last2=Suzumiya|first2=J.|last3=Shimazaki|first3=K.|last4=Kato|first4=A.|last5=Tanaka|first5=T.|last6=Kanda|first6=M.|last7=Kikuchi|first7=M.|date=1997-11|title=Nasal T/NK cell lymphomas commonly express perforin and Fas ligand: important mediators of tissue damage|url=https://pubmed.ncbi.nlm.nih.gov/9416485|journal=Histopathology|volume=31|issue=5|pages=444–450|doi=10.1046/j.1365-2559.1997.2880887.x|issn=0309-0167|pmid=9416485}}</ref><ref>{{Cite journal|last=Takata|first=Katsuyoshi|last2=Hong|first2=Min-Eui|last3=Sitthinamsuwan|first3=Panitta|last4=Loong|first4=Florence|last5=Tan|first5=Soo-Yong|last6=Liau|first6=Jau-Yu|last7=Hsieh|first7=Pin-Pen|last8=Ng|first8=Siok-Bian|last9=Yang|first9=Sheau-Fang|date=2015-01|title=Primary cutaneous NK/T-cell lymphoma, nasal type and CD56-positive peripheral T-cell lymphoma: a cellular lineage and clinicopathologic study of 60 patients from Asia|url=https://pubmed.ncbi.nlm.nih.gov/25188863|journal=The American Journal of Surgical Pathology|volume=39|issue=1|pages=1–12|doi=10.1097/PAS.0000000000000312|issn=1532-0979|pmid=25188863}}</ref><ref>{{Cite journal|last=Kuo|first=Tseng-Tong|last2=Shih|first2=Lee-Yung|last3=Tsang|first3=Ngan-Ming|date=2004-10|title=Nasal NK/T cell lymphoma in Taiwan: a clinicopathologic study of 22 cases, with analysis of histologic subtypes, Epstein-Barr virus LMP-1 gene association, and treatment modalities|url=https://pubmed.ncbi.nlm.nih.gov/15494863|journal=International Journal of Surgical Pathology|volume=12|issue=4|pages=375–387|doi=10.1177/106689690401200410|issn=1066-8969|pmid=15494863}}</ref>.
|Positive (subset)||TCR αβ/γδ, HLA-DR, CD25, pSTAT3, CXCL13, IRF4/MUM1, CD16, Fas, FasL, MATK, CD30<ref name=":25">{{Cite journal|last=Li|first=Shaoying|last2=Feng|first2=Xiaoli|last3=Li|first3=Ting|last4=Zhang|first4=Shuang|last5=Zuo|first5=Zhuang|last6=Lin|first6=Pei|last7=Konoplev|first7=Sergej|last8=Bueso-Ramos|first8=Carlos E.|last9=Vega|first9=Francisco|date=2013-01|title=Extranodal NK/T-cell lymphoma, nasal type: a report of 73 cases at MD Anderson Cancer Center|url=https://pubmed.ncbi.nlm.nih.gov/23232851|journal=The American Journal of Surgical Pathology|volume=37|issue=1|pages=14–23|doi=10.1097/PAS.0b013e31826731b5|issn=1532-0979|pmid=23232851}}</ref><ref name=":26">{{Cite journal|last=Jhuang|first=Jie-Yang|last2=Chang|first2=Sheng-Tsung|last3=Weng|first3=Shih-Feng|last4=Pan|first4=Shien-Tung|last5=Chu|first5=Pei-Yi|last6=Hsieh|first6=Pin-Pen|last7=Wei|first7=Chih-Hsin|last8=Chou|first8=Shih-Cheng|last9=Koo|first9=Chiew-Loon|date=2015-02|title=Extranodal natural killer/T-cell lymphoma, nasal type in Taiwan: a relatively higher frequency of T-cell lineage and poor survival for extranasal tumors|url=https://pubmed.ncbi.nlm.nih.gov/25554090|journal=Human Pathology|volume=46|issue=2|pages=313–321|doi=10.1016/j.humpath.2014.11.008|issn=1532-8392|pmid=25554090}}</ref><ref name=":27">{{Cite journal|last=Pongpruttipan|first=Tawatchai|last2=Sukpanichnant|first2=Sanya|last3=Assanasen|first3=Thamathorn|last4=Wannakrairot|first4=Pongsak|last5=Boonsakan|first5=Paisarn|last6=Kanoksil|first6=Wasana|last7=Kayasut|first7=Kanita|last8=Mitarnun|first8=Winyou|last9=Khuhapinant|first9=Archrob|date=2012-04|title=Extranodal NK/T-cell lymphoma, nasal type, includes cases of natural killer cell and αβ, γδ, and αβ/γδ T-cell origin: a comprehensive clinicopathologic and phenotypic study|url=https://pubmed.ncbi.nlm.nih.gov/22314189|journal=The American Journal of Surgical Pathology|volume=36|issue=4|pages=481–499|doi=10.1097/PAS.0b013e31824433d8|issn=1532-0979|pmid=22314189}}</ref><ref name=":28">{{Cite journal|last=Jaffe|first=E. S.|last2=Chan|first2=J. K.|last3=Su|first3=I. J.|last4=Frizzera|first4=G.|last5=Mori|first5=S.|last6=Feller|first6=A. C.|last7=Ho|first7=F. C.|date=1996-01|title=Report of the Workshop on Nasal and Related Extranodal Angiocentric T/Natural Killer Cell Lymphomas. Definitions, differential diagnosis, and epidemiology|url=https://pubmed.ncbi.nlm.nih.gov/8540601|journal=The American Journal of Surgical Pathology|volume=20|issue=1|pages=103–111|doi=10.1097/00000478-199601000-00012|issn=0147-5185|pmid=8540601}}</ref><ref name=":29">{{Cite journal|last=Ohshima|first=K.|last2=Suzumiya|first2=J.|last3=Shimazaki|first3=K.|last4=Kato|first4=A.|last5=Tanaka|first5=T.|last6=Kanda|first6=M.|last7=Kikuchi|first7=M.|date=1997-11|title=Nasal T/NK cell lymphomas commonly express perforin and Fas ligand: important mediators of tissue damage|url=https://pubmed.ncbi.nlm.nih.gov/9416485|journal=Histopathology|volume=31|issue=5|pages=444–450|doi=10.1046/j.1365-2559.1997.2880887.x|issn=0309-0167|pmid=9416485}}</ref><ref name=":30">{{Cite journal|last=Takata|first=Katsuyoshi|last2=Hong|first2=Min-Eui|last3=Sitthinamsuwan|first3=Panitta|last4=Loong|first4=Florence|last5=Tan|first5=Soo-Yong|last6=Liau|first6=Jau-Yu|last7=Hsieh|first7=Pin-Pen|last8=Ng|first8=Siok-Bian|last9=Yang|first9=Sheau-Fang|date=2015-01|title=Primary cutaneous NK/T-cell lymphoma, nasal type and CD56-positive peripheral T-cell lymphoma: a cellular lineage and clinicopathologic study of 60 patients from Asia|url=https://pubmed.ncbi.nlm.nih.gov/25188863|journal=The American Journal of Surgical Pathology|volume=39|issue=1|pages=1–12|doi=10.1097/PAS.0000000000000312|issn=1532-0979|pmid=25188863}}</ref><ref name=":31">{{Cite journal|last=Kuo|first=Tseng-Tong|last2=Shih|first2=Lee-Yung|last3=Tsang|first3=Ngan-Ming|date=2004-10|title=Nasal NK/T cell lymphoma in Taiwan: a clinicopathologic study of 22 cases, with analysis of histologic subtypes, Epstein-Barr virus LMP-1 gene association, and treatment modalities|url=https://pubmed.ncbi.nlm.nih.gov/15494863|journal=International Journal of Surgical Pathology|volume=12|issue=4|pages=375–387|doi=10.1177/106689690401200410|issn=1066-8969|pmid=15494863}}</ref>.
|-
|-
|Negative (universal)||CD4, CD8
|Negative (universal)||CD4, CD8
Line 111: Line 111:
|}
|}


==Chromosomal Rearrangements (Gene Fusions)==
==WHO Essential and Desirable Genetic Diagnostic Criteria==
<span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span>
{| class="wikitable"
|+
|WHO Essential Criteria (Genetics)*
|
|-
|WHO Desirable Criteria (Genetics)*
|
|-
|Other Classification
|
|}
<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
==Related Terminology==
<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>
{| class="wikitable"
|+
|Acceptable
|
|-
|Not Recommended
|
|}
 
==Gene Rearrangements==


{| class="wikitable sortable"
{| class="wikitable sortable"
Line 128: Line 153:
|}
|}
==Individual Region Genomic Gain / Loss / LOH==
==Individual Region Genomic Gain/Loss/LOH==


{| class="wikitable sortable"
{| class="wikitable sortable"
Line 149: Line 174:
Other less common chromosomal alterations include gain of 1p, 2q, 6p, 10q, 11q, 12q, 13q, 17q, 19p, 20q, and Xp; and loss of 1p36, 2p16, 4q12, 4q31-32, 5p14, 5q34-35, 6q13-14, 6q16-27, 11q22-23, 12q, 13q12-14, 13q14-34, 17p13, and entire chromosome X<ref>{{Cite journal|last=Nakashima|first=Yasuhiro|last2=Tagawa|first2=Hiroyuki|last3=Suzuki|first3=Ritsuro|last4=Karnan|first4=Sivasundaram|last5=Karube|first5=Kennosuke|last6=Ohshima|first6=Koichi|last7=Muta|first7=Koichiro|last8=Nawata|first8=Hajime|last9=Morishima|first9=Yasuo|date=2005-11|title=Genome-wide array-based comparative genomic hybridization of natural killer cell lymphoma/leukemia: different genomic alteration patterns of aggressive NK-cell leukemia and extranodal Nk/T-cell lymphoma, nasal type|url=https://pubmed.ncbi.nlm.nih.gov/16049916|journal=Genes, Chromosomes & Cancer|volume=44|issue=3|pages=247–255|doi=10.1002/gcc.20245|issn=1045-2257|pmid=16049916}}</ref><ref>{{Cite journal|last=Siu|first=L. L.|last2=Chan|first2=V.|last3=Chan|first3=J. K.|last4=Wong|first4=K. F.|last5=Liang|first5=R.|last6=Kwong|first6=Y. L.|date=2000-12|title=Consistent patterns of allelic loss in natural killer cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/11106552|journal=The American Journal of Pathology|volume=157|issue=6|pages=1803–1809|doi=10.1016/S0002-9440(10)64818-3|issn=0002-9440|pmc=1885756|pmid=11106552}}</ref><ref>{{Cite journal|last=Siu|first=L. L.|last2=Wong|first2=K. F.|last3=Chan|first3=J. K.|last4=Kwong|first4=Y. L.|date=1999-11|title=Comparative genomic hybridization analysis of natural killer cell lymphoma/leukemia. Recognition of consistent patterns of genetic alterations|url=https://pubmed.ncbi.nlm.nih.gov/10550295|journal=The American Journal of Pathology|volume=155|issue=5|pages=1419–1425|doi=10.1016/S0002-9440(10)65454-5|issn=0002-9440|pmc=1866965|pmid=10550295}}</ref><ref>{{Cite journal|last=Wong|first=K. F.|last2=Zhang|first2=Y. M.|last3=Chan|first3=J. K.|date=1999-07|title=Cytogenetic abnormalities in natural killer cell lymphoma/leukaemia--is there a consistent pattern?|url=https://pubmed.ncbi.nlm.nih.gov/10439361|journal=Leukemia & Lymphoma|volume=34|issue=3-4|pages=241–250|doi=10.3109/10428199909050949|issn=1042-8194|pmid=10439361}}</ref><ref>{{Cite journal|last=Ko|first=Y. H.|last2=Choi|first2=K. E.|last3=Han|first3=J. H.|last4=Kim|first4=J. M.|last5=Ree|first5=H. J.|date=2001-04-15|title=Comparative genomic hybridization study of nasal-type NK/T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/11309817|journal=Cytometry|volume=46|issue=2|pages=85–91|doi=10.1002/cyto.1069|issn=0196-4763|pmid=11309817}}</ref>.
Other less common chromosomal alterations include gain of 1p, 2q, 6p, 10q, 11q, 12q, 13q, 17q, 19p, 20q, and Xp; and loss of 1p36, 2p16, 4q12, 4q31-32, 5p14, 5q34-35, 6q13-14, 6q16-27, 11q22-23, 12q, 13q12-14, 13q14-34, 17p13, and entire chromosome X<ref>{{Cite journal|last=Nakashima|first=Yasuhiro|last2=Tagawa|first2=Hiroyuki|last3=Suzuki|first3=Ritsuro|last4=Karnan|first4=Sivasundaram|last5=Karube|first5=Kennosuke|last6=Ohshima|first6=Koichi|last7=Muta|first7=Koichiro|last8=Nawata|first8=Hajime|last9=Morishima|first9=Yasuo|date=2005-11|title=Genome-wide array-based comparative genomic hybridization of natural killer cell lymphoma/leukemia: different genomic alteration patterns of aggressive NK-cell leukemia and extranodal Nk/T-cell lymphoma, nasal type|url=https://pubmed.ncbi.nlm.nih.gov/16049916|journal=Genes, Chromosomes & Cancer|volume=44|issue=3|pages=247–255|doi=10.1002/gcc.20245|issn=1045-2257|pmid=16049916}}</ref><ref>{{Cite journal|last=Siu|first=L. L.|last2=Chan|first2=V.|last3=Chan|first3=J. K.|last4=Wong|first4=K. F.|last5=Liang|first5=R.|last6=Kwong|first6=Y. L.|date=2000-12|title=Consistent patterns of allelic loss in natural killer cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/11106552|journal=The American Journal of Pathology|volume=157|issue=6|pages=1803–1809|doi=10.1016/S0002-9440(10)64818-3|issn=0002-9440|pmc=1885756|pmid=11106552}}</ref><ref>{{Cite journal|last=Siu|first=L. L.|last2=Wong|first2=K. F.|last3=Chan|first3=J. K.|last4=Kwong|first4=Y. L.|date=1999-11|title=Comparative genomic hybridization analysis of natural killer cell lymphoma/leukemia. Recognition of consistent patterns of genetic alterations|url=https://pubmed.ncbi.nlm.nih.gov/10550295|journal=The American Journal of Pathology|volume=155|issue=5|pages=1419–1425|doi=10.1016/S0002-9440(10)65454-5|issn=0002-9440|pmc=1866965|pmid=10550295}}</ref><ref>{{Cite journal|last=Wong|first=K. F.|last2=Zhang|first2=Y. M.|last3=Chan|first3=J. K.|date=1999-07|title=Cytogenetic abnormalities in natural killer cell lymphoma/leukaemia--is there a consistent pattern?|url=https://pubmed.ncbi.nlm.nih.gov/10439361|journal=Leukemia & Lymphoma|volume=34|issue=3-4|pages=241–250|doi=10.3109/10428199909050949|issn=1042-8194|pmid=10439361}}</ref><ref>{{Cite journal|last=Ko|first=Y. H.|last2=Choi|first2=K. E.|last3=Han|first3=J. H.|last4=Kim|first4=J. M.|last5=Ree|first5=H. J.|date=2001-04-15|title=Comparative genomic hybridization study of nasal-type NK/T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/11309817|journal=Cytometry|volume=46|issue=2|pages=85–91|doi=10.1002/cyto.1069|issn=0196-4763|pmid=11309817}}</ref>.


==Characteristic Chromosomal Patterns==
==Characteristic Chromosomal or Other Global Mutational Patterns==


{| class="wikitable sortable"
{| class="wikitable sortable"
Line 171: Line 196:
|N/A
|N/A
|}
|}
==Gene Mutations (SNV / INDEL)==
==Gene Mutations (SNV/INDEL)==


{| class="wikitable sortable"
{| class="wikitable sortable"
Line 186: Line 211:
|
|
|
|
|
|Unknown
|
|Unknown
|Pan-JAK and selective JAK3 inhibitors have been suggested as potential therapeutic options<ref name=":10" /><ref>{{Cite journal|last=Nairismägi|first=M.-L.|last2=Gerritsen|first2=M. E.|last3=Li|first3=Z. M.|last4=Wijaya|first4=G. C.|last5=Chia|first5=B. K. H.|last6=Laurensia|first6=Y.|last7=Lim|first7=J. Q.|last8=Yeoh|first8=K. W.|last9=Yao|first9=X. S.|date=2018-05|title=Oncogenic activation of JAK3-STAT signaling confers clinical sensitivity to PRN371, a novel selective and potent JAK3 inhibitor, in natural killer/T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/29434279|journal=Leukemia|volume=32|issue=5|pages=1147–1156|doi=10.1038/s41375-017-0004-x|issn=1476-5551|pmc=5940653|pmid=29434279}}</ref>. [https://clinicaltrials.gov/study/NCT02974647 Clinical trials evaluating JAK inhibitors] are in progress.
|Pan-JAK and selective JAK3 inhibitors have been suggested as potential therapeutic options<ref name=":10" /><ref>{{Cite journal|last=Nairismägi|first=M.-L.|last2=Gerritsen|first2=M. E.|last3=Li|first3=Z. M.|last4=Wijaya|first4=G. C.|last5=Chia|first5=B. K. H.|last6=Laurensia|first6=Y.|last7=Lim|first7=J. Q.|last8=Yeoh|first8=K. W.|last9=Yao|first9=X. S.|date=2018-05|title=Oncogenic activation of JAK3-STAT signaling confers clinical sensitivity to PRN371, a novel selective and potent JAK3 inhibitor, in natural killer/T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/29434279|journal=Leukemia|volume=32|issue=5|pages=1147–1156|doi=10.1038/s41375-017-0004-x|issn=1476-5551|pmc=5940653|pmid=29434279}}</ref>. [https://clinicaltrials.gov/study/NCT02974647 Clinical trials evaluating JAK inhibitors] are in progress.
|
|
Line 193: Line 218:
|''STAT3''<ref name=":2">{{Cite journal|last=Jiang|first=Lu|last2=Gu|first2=Zhao-Hui|last3=Yan|first3=Zi-Xun|last4=Zhao|first4=Xia|last5=Xie|first5=Yin-Yin|last6=Zhang|first6=Zi-Guan|last7=Pan|first7=Chun-Ming|last8=Hu|first8=Yuan|last9=Cai|first9=Chang-Ping|date=2015-09|title=Exome sequencing identifies somatic mutations of DDX3X in natural killer/T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26192917|journal=Nature Genetics|volume=47|issue=9|pages=1061–1066|doi=10.1038/ng.3358|issn=1546-1718|pmid=26192917}}</ref><ref name=":3">{{Cite journal|last=Küçük|first=Can|last2=Jiang|first2=Bei|last3=Hu|first3=Xiaozhou|last4=Zhang|first4=Wenyan|last5=Chan|first5=John K. C.|last6=Xiao|first6=Wenming|last7=Lack|first7=Nathan|last8=Alkan|first8=Can|last9=Williams|first9=John C.|date=2015-01-14|title=Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells|url=https://pubmed.ncbi.nlm.nih.gov/25586472|journal=Nature Communications|volume=6|pages=6025|doi=10.1038/ncomms7025|issn=2041-1723|pmc=7743911|pmid=25586472}}</ref><ref name=":4">{{Cite journal|last=Lee|first=Seungbok|last2=Park|first2=Ha Young|last3=Kang|first3=So Young|last4=Kim|first4=Seok Jin|last5=Hwang|first5=Jinha|last6=Lee|first6=Seungho|last7=Kwak|first7=Soo Heon|last8=Park|first8=Kyong Soo|last9=Yoo|first9=Hae Yong|date=2015-07-10|title=Genetic alterations of JAK/STAT cascade and histone modification in extranodal NK/T-cell lymphoma nasal type|url=https://pubmed.ncbi.nlm.nih.gov/25980440|journal=Oncotarget|volume=6|issue=19|pages=17764–17776|doi=10.18632/oncotarget.3776|issn=1949-2553|pmc=4627344|pmid=25980440}}</ref>
|''STAT3''<ref name=":2">{{Cite journal|last=Jiang|first=Lu|last2=Gu|first2=Zhao-Hui|last3=Yan|first3=Zi-Xun|last4=Zhao|first4=Xia|last5=Xie|first5=Yin-Yin|last6=Zhang|first6=Zi-Guan|last7=Pan|first7=Chun-Ming|last8=Hu|first8=Yuan|last9=Cai|first9=Chang-Ping|date=2015-09|title=Exome sequencing identifies somatic mutations of DDX3X in natural killer/T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26192917|journal=Nature Genetics|volume=47|issue=9|pages=1061–1066|doi=10.1038/ng.3358|issn=1546-1718|pmid=26192917}}</ref><ref name=":3">{{Cite journal|last=Küçük|first=Can|last2=Jiang|first2=Bei|last3=Hu|first3=Xiaozhou|last4=Zhang|first4=Wenyan|last5=Chan|first5=John K. C.|last6=Xiao|first6=Wenming|last7=Lack|first7=Nathan|last8=Alkan|first8=Can|last9=Williams|first9=John C.|date=2015-01-14|title=Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells|url=https://pubmed.ncbi.nlm.nih.gov/25586472|journal=Nature Communications|volume=6|pages=6025|doi=10.1038/ncomms7025|issn=2041-1723|pmc=7743911|pmid=25586472}}</ref><ref name=":4">{{Cite journal|last=Lee|first=Seungbok|last2=Park|first2=Ha Young|last3=Kang|first3=So Young|last4=Kim|first4=Seok Jin|last5=Hwang|first5=Jinha|last6=Lee|first6=Seungho|last7=Kwak|first7=Soo Heon|last8=Park|first8=Kyong Soo|last9=Yoo|first9=Hae Yong|date=2015-07-10|title=Genetic alterations of JAK/STAT cascade and histone modification in extranodal NK/T-cell lymphoma nasal type|url=https://pubmed.ncbi.nlm.nih.gov/25980440|journal=Oncotarget|volume=6|issue=19|pages=17764–17776|doi=10.18632/oncotarget.3776|issn=1949-2553|pmc=4627344|pmid=25980440}}</ref>
|Oncogene
|Oncogene
|26%<ref name=":4" />
|6-26%<ref name=":3" /><ref name=":4" />
|
|
|
|
|
|
|Unknown
|Unknown
|STAT3 inhibitor may have potential therapeutic benefit in patients with STAT3 activating mutation<ref>{{Cite journal|last=Wang|first=Yali|last2=Zhou|first2=Wenbo|last3=Chen|first3=Jianfeng|last4=Chen|first4=Jinghong|last5=Deng|first5=Peng|last6=Chen|first6=Huang|last7=Sun|first7=Yichen|last8=Yu|first8=Zhaoliang|last9=Pang|first9=Diwen|date=2023-08|title=Preclinical characterization of WB737, a potent and selective STAT3 inhibitor, in natural killer/T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/37334274|journal=MedComm|volume=4|issue=4|pages=e284|doi=10.1002/mco2.284|issn=2688-2663|pmc=PMC10274570|pmid=37334274}}</ref>.
|STAT3 inhibitor may have potential therapeutic benefit in patients with STAT3 activating mutation<ref>{{Cite journal|last=Wang|first=Yali|last2=Zhou|first2=Wenbo|last3=Chen|first3=Jianfeng|last4=Chen|first4=Jinghong|last5=Deng|first5=Peng|last6=Chen|first6=Huang|last7=Sun|first7=Yichen|last8=Yu|first8=Zhaoliang|last9=Pang|first9=Diwen|date=2023-08|title=Preclinical characterization of WB737, a potent and selective STAT3 inhibitor, in natural killer/T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/37334274|journal=MedComm|volume=4|issue=4|pages=e284|doi=10.1002/mco2.284|issn=2688-2663|pmc=PMC10274570|pmid=37334274}}</ref>.
|
|
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|''STAT5B''<ref name=":2" /><ref name=":3" />
|''STAT5B''<ref name=":2" /><ref name=":3" />
|Oncogene
|Oncogene
|6%<ref name=":3" />
|
|
|
|
|
|Unknown
|
|Unknown
|
|Unknown
|
|
|
|-
|-
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|
|
|
|
|
|Unknown
|
|Unknown
|
|Unknown
|
|
|-
|-
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|
|
|
|
|
|Unknown
|
|Unknown
|
|Unknown
|
|
|-
|-
|''RUNX3''<ref>{{Cite journal|last=Selvarajan|first=V.|last2=Osato|first2=M.|last3=Nah|first3=G. S. S.|last4=Yan|first4=J.|last5=Chung|first5=T.-H.|last6=Voon|first6=D. C.-C.|last7=Ito|first7=Y.|last8=Ham|first8=M. F.|last9=Salto-Tellez|first9=M.|date=2017-10|title=RUNX3 is oncogenic in natural killer/T-cell lymphoma and is transcriptionally regulated by MYC|url=https://pubmed.ncbi.nlm.nih.gov/28119527|journal=Leukemia|volume=31|issue=10|pages=2219–2227|doi=10.1038/leu.2017.40|issn=1476-5551|pmc=5629367|pmid=28119527}}</ref>
|''PDGFRA''<ref name=":13" />
|Oncogene
|
|
|
|
|
|
|Unknown
|Unknown
|Unknown
|
|
|-
|''EZH2''<ref>{{Cite journal|last=Yan|first=Junli|last2=Li|first2=Boheng|last3=Lin|first3=Baohong|last4=Lee|first4=Pei Tsung|last5=Chung|first5=Tae-Hoon|last6=Tan|first6=Joy|last7=Bi|first7=Chonglei|last8=Lee|first8=Xue Ting|last9=Selvarajan|first9=Viknesvaran|date=2016-08-18|title=EZH2 phosphorylation by JAK3 mediates a switch to noncanonical function in natural killer/T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/27297789|journal=Blood|volume=128|issue=7|pages=948–958|doi=10.1182/blood-2016-01-690701|issn=1528-0020|pmid=27297789}}</ref>
|Oncogene
|
|
|
|
|
|
|Unknown
|Unknown
|Unknown
|
|
|-
|-
|''PDGFRA''<ref name=":13" />
|''RAS/KRAS/HRAS''
|Oncogene
|Oncogene
|<5%<ref name=":14">{{Cite journal|last=Hoshida|first=Yoshihiko|last2=Hongyo|first2=Tadashi|last3=Jia|first3=Xinshan|last4=He|first4=Yanjiao|last5=Hasui|first5=Kazuhisa|last6=Dong|first6=Zhiming|last7=Luo|first7=Wen-Juan|last8=Ham|first8=Maria Francisca|last9=Nomura|first9=Taisei|date=2003-03|title=Analysis of p53, K-ras, c-kit, and beta-catenin gene mutations in sinonasal NK/T cell lymphoma in northeast district of China|url=https://pubmed.ncbi.nlm.nih.gov/12824925|journal=Cancer Science|volume=94|issue=3|pages=297–301|doi=10.1111/j.1349-7006.2003.tb01436.x|issn=1347-9032|pmc=PMC11160272|pmid=12824925}}</ref><ref>{{Cite journal|last=Takahara|first=Miki|last2=Kishibe|first2=Kan|last3=Bandoh|first3=Nobuyuki|last4=Nonaka|first4=Satoshi|last5=Harabuchi|first5=Yasuaki|date=2004-01|title=P53, N- and K-Ras, and beta-catenin gene mutations and prognostic factors in nasal NK/T-cell lymphoma from Hokkaido, Japan|url=https://pubmed.ncbi.nlm.nih.gov/14745729|journal=Human Pathology|volume=35|issue=1|pages=86–95|doi=10.1016/j.humpath.2003.08.025|issn=0046-8177|pmid=14745729}}</ref>
|
|
|
|
|Unknown
|Unknown
|Unknown
|
|
|-
|''FAS''
|Oncogene
|50-60%<ref>{{Cite journal|last=Shen|first=Lijun|last2=Liang|first2=Anthony C. T.|last3=Lu|first3=Liwei|last4=Au|first4=Wing Yan|last5=Kwong|first5=Yok-Lam|last6=Liang|first6=Raymond H. S.|last7=Srivastava|first7=Gopesh|date=2002-12|title=Frequent deletion of Fas gene sequences encoding death and transmembrane domains in nasal natural killer/T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/12466128|journal=The American Journal of Pathology|volume=161|issue=6|pages=2123–2131|doi=10.1016/S0002-9440(10)64490-2|issn=0002-9440|pmc=1850920|pmid=12466128}}</ref><ref>{{Cite journal|last=Takakuwa|first=Tetsuya|last2=Dong|first2=Zhiming|last3=Nakatsuka|first3=Shinichi|last4=Kojya|first4=Shizuo|last5=Harabuchi|first5=Yasuaki|last6=Yang|first6=Woo-Ick|last7=Nagata|first7=Shigekazu|last8=Aozasa|first8=Katsuyuki|date=2002-07-11|title=Frequent mutations of Fas gene in nasal NK/T cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/12096347|journal=Oncogene|volume=21|issue=30|pages=4702–4705|doi=10.1038/sj.onc.1205571|issn=0950-9232|pmid=12096347}}</ref>
|
|
|
|
|
|Unknown
|Unknown
|Unknown
|
|
|-
|-
|''EZH2''<ref>{{Cite journal|last=Yan|first=Junli|last2=Li|first2=Boheng|last3=Lin|first3=Baohong|last4=Lee|first4=Pei Tsung|last5=Chung|first5=Tae-Hoon|last6=Tan|first6=Joy|last7=Bi|first7=Chonglei|last8=Lee|first8=Xue Ting|last9=Selvarajan|first9=Viknesvaran|date=2016-08-18|title=EZH2 phosphorylation by JAK3 mediates a switch to noncanonical function in natural killer/T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/27297789|journal=Blood|volume=128|issue=7|pages=948–958|doi=10.1182/blood-2016-01-690701|issn=1528-0020|pmid=27297789}}</ref>
|''KIT''
|Oncogene
|Oncogene
|5-71% (China)
22% (Japan)<ref name=":14" /><ref>{{Cite journal|last=Hongyo|first=T.|last2=Li|first2=T.|last3=Syaifudin|first3=M.|last4=Baskar|first4=R.|last5=Ikeda|first5=H.|last6=Kanakura|first6=Y.|last7=Aozasa|first7=K.|last8=Nomura|first8=T.|date=2000-05-01|title=Specific c-kit mutations in sinonasal natural killer/T-cell lymphoma in China and Japan|url=https://pubmed.ncbi.nlm.nih.gov/10811105|journal=Cancer Research|volume=60|issue=9|pages=2345–2347|issn=0008-5472|pmid=10811105}}</ref>
|
|
|
|
|Unknown
|Unknown
|Unknown
|
|
|-
|''CTNNB1''
|Oncogene
|16-30%<ref name=":14" /><ref>{{Cite journal|last=Sugimoto|first=Kei-ji|last2=Kawamata|first2=Norihiko|last3=Sakajiri|first3=Sakura|last4=Oshimi|first4=Kazuo|date=2002-11|title=Molecular analysis of oncogenes, ras family genes (N-ras, K-ras, H-ras), myc family genes (c-myc, N-myc) and mdm2 in natural killer cell neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/12460470|journal=Japanese Journal of Cancer Research: Gann|volume=93|issue=11|pages=1270–1277|doi=10.1111/j.1349-7006.2002.tb01234.x|issn=0910-5050|pmc=5926889|pmid=12460470}}</ref>
|
|
|
|
|
|Unknown
|Unknown
|Unknown
|
|
|-
|-
|''DDX3X''<ref name=":2" />
|''DDX3X''<ref name=":2" />
|Other (RNA helicase)
|Epigenetic modifier (RNA helicase)
|20%<ref name=":2" />
|20%<ref name=":2" />
|
|
|
|
|Unknown
|Unknown
|Unknown
|
|
|-
|''KMT2D (MLL2)''<ref name=":2" />
|Epigenetic modifier
|38.2%<ref name=":4" />
|
|
|
|
|Unknown
|Unknown
|Unknown
|
|
|-
|-
|''TP53''<ref name=":2" />
|''ARID1A''<ref name=":2" />
|Tumor suppressor gene
|Epigenetic modifier
|24-62%<ref name=":11">{{Cite journal|last=Quintanilla-Martinez|first=L.|last2=Kremer|first2=M.|last3=Keller|first3=G.|last4=Nathrath|first4=M.|last5=Gamboa-Dominguez|first5=A.|last6=Meneses|first6=A.|last7=Luna-Contreras|first7=L.|last8=Cabras|first8=A.|last9=Hoefler|first9=H.|date=2001-12|title=p53 Mutations in nasal natural killer/T-cell lymphoma from Mexico: association with large cell morphology and advanced disease|url=https://pubmed.ncbi.nlm.nih.gov/11733360|journal=The American Journal of Pathology|volume=159|issue=6|pages=2095–2105|doi=10.1016/S0002-9440(10)63061-1|issn=0002-9440|pmc=1850589|pmid=11733360}}</ref><ref name=":8">{{Cite journal|last=Hongyo|first=Tadashi|last2=Hoshida|first2=Yoshihiko|last3=Nakatsuka|first3=Shin-Ichi|last4=Syaifudin|first4=Mukh|last5=Kojya|first5=Shizuo|last6=Yang|first6=Woo-Ick|last7=Min|first7=Yoo-Hong|last8=Chan|first8=Heekyung|last9=Kim|first9=Chan Hwan|date=2005-02|title=p53, K-ras, c-kit and beta-catenin gene mutations in sinonasal NK/T-cell lymphoma in Korea and Japan|url=https://pubmed.ncbi.nlm.nih.gov/15643509|journal=Oncology Reports|volume=13|issue=2|pages=265–271|issn=1021-335X|pmid=15643509}}</ref>
|
|
|
|Unknown
|Unknown
|Unknown
|
|
|-
|''EP300''<ref name=":2" />
|Epigenetic modifier
|
|
|
|
|Yes, associated with advanced stage disease<ref name=":11" />.
|
|
|Unknown
|Unknown
|Unknown
|
|
|-
|-
|''MGA''<ref name=":2" />
|''ASXL3''<ref name=":2" />
|Tumor suppressor gene
|Epigenetic modifier
|
|
|
|
|
|
|Unknown
|Unknown
|Unknown
|
|
|-
|''BCOR''<ref name=":4" />
|Epigenetic modifier
|38.2%<ref name=":4" />
|
|
|
|
|Unknown
|Unknown
|Unknown
|
|
|-
|-
|''PRDM1''<ref name=":9">{{Cite journal|last=Huang|first=Yenlin|last2=de Leval|first2=Laurence|last3=Gaulard|first3=Philippe|date=2013-03|title=Molecular underpinning of extranodal NK/T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/23768641|journal=Best Practice & Research. Clinical Haematology|volume=26|issue=1|pages=57–74|doi=10.1016/j.beha.2013.04.006|issn=1532-1924|pmid=23768641}}</ref><ref name=":7" /><ref>{{Cite journal|last=Küçük|first=Can|last2=Iqbal|first2=Javeed|last3=Hu|first3=Xiaozhou|last4=Gaulard|first4=Phillip|last5=De Leval|first5=Laurence|last6=Srivastava|first6=Gopesh|last7=Au|first7=Wing Yan|last8=McKeithan|first8=Timothy W.|last9=Chan|first9=Wing C.|date=2011-12-13|title=PRDM1 is a tumor suppressor gene in natural killer cell malignancies|url=https://pubmed.ncbi.nlm.nih.gov/22143801|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=108|issue=50|pages=20119–20124|doi=10.1073/pnas.1115128108|issn=1091-6490|pmc=3250125|pmid=22143801}}</ref>
|''TP53''<ref name=":2" />
|Tumor suppressor gene
|Tumor suppressor gene
|24-62%<ref name=":11">{{Cite journal|last=Quintanilla-Martinez|first=L.|last2=Kremer|first2=M.|last3=Keller|first3=G.|last4=Nathrath|first4=M.|last5=Gamboa-Dominguez|first5=A.|last6=Meneses|first6=A.|last7=Luna-Contreras|first7=L.|last8=Cabras|first8=A.|last9=Hoefler|first9=H.|date=2001-12|title=p53 Mutations in nasal natural killer/T-cell lymphoma from Mexico: association with large cell morphology and advanced disease|url=https://pubmed.ncbi.nlm.nih.gov/11733360|journal=The American Journal of Pathology|volume=159|issue=6|pages=2095–2105|doi=10.1016/S0002-9440(10)63061-1|issn=0002-9440|pmc=1850589|pmid=11733360}}</ref><ref name=":8">{{Cite journal|last=Hongyo|first=Tadashi|last2=Hoshida|first2=Yoshihiko|last3=Nakatsuka|first3=Shin-Ichi|last4=Syaifudin|first4=Mukh|last5=Kojya|first5=Shizuo|last6=Yang|first6=Woo-Ick|last7=Min|first7=Yoo-Hong|last8=Chan|first8=Heekyung|last9=Kim|first9=Chan Hwan|date=2005-02|title=p53, K-ras, c-kit and beta-catenin gene mutations in sinonasal NK/T-cell lymphoma in Korea and Japan|url=https://pubmed.ncbi.nlm.nih.gov/15643509|journal=Oncology Reports|volume=13|issue=2|pages=265–271|issn=1021-335X|pmid=15643509}}</ref>
|
|
|
|
|Unknown
|Yes, associated with advanced stage disease<ref name=":11" />.
|Unknown
|
|
|-
|''RUNX3''<ref>{{Cite journal|last=Selvarajan|first=V.|last2=Osato|first2=M.|last3=Nah|first3=G. S. S.|last4=Yan|first4=J.|last5=Chung|first5=T.-H.|last6=Voon|first6=D. C.-C.|last7=Ito|first7=Y.|last8=Ham|first8=M. F.|last9=Salto-Tellez|first9=M.|date=2017-10|title=RUNX3 is oncogenic in natural killer/T-cell lymphoma and is transcriptionally regulated by MYC|url=https://pubmed.ncbi.nlm.nih.gov/28119527|journal=Leukemia|volume=31|issue=10|pages=2219–2227|doi=10.1038/leu.2017.40|issn=1476-5551|pmc=5629367|pmid=28119527}}</ref>
|Tumor suppressor gene
|
|
|
|
|
|
|Unknown
|Unknown
|Unknown
|
|
|-
|-
|''ATG5''<ref name=":9" />
|''MGA''<ref name=":2" />
|Tumor suppressor gene
|Tumor suppressor gene
|
|
|
|
|
|
|Unknown
|Unknown
|Unknown
|
|
|-
|''PRDM1''<ref name=":9">{{Cite journal|last=Huang|first=Yenlin|last2=de Leval|first2=Laurence|last3=Gaulard|first3=Philippe|date=2013-03|title=Molecular underpinning of extranodal NK/T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/23768641|journal=Best Practice & Research. Clinical Haematology|volume=26|issue=1|pages=57–74|doi=10.1016/j.beha.2013.04.006|issn=1532-1924|pmid=23768641}}</ref><ref name=":7" /><ref>{{Cite journal|last=Küçük|first=Can|last2=Iqbal|first2=Javeed|last3=Hu|first3=Xiaozhou|last4=Gaulard|first4=Phillip|last5=De Leval|first5=Laurence|last6=Srivastava|first6=Gopesh|last7=Au|first7=Wing Yan|last8=McKeithan|first8=Timothy W.|last9=Chan|first9=Wing C.|date=2011-12-13|title=PRDM1 is a tumor suppressor gene in natural killer cell malignancies|url=https://pubmed.ncbi.nlm.nih.gov/22143801|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=108|issue=50|pages=20119–20124|doi=10.1073/pnas.1115128108|issn=1091-6490|pmc=3250125|pmid=22143801}}</ref>
|Tumor suppressor gene
|Methylated in NK-92, KHYG-1, SNK-1, SNK-6 cell lines, 12/17 cases; Deleted in 8/18 cases; Mutated in NK-92 and KAI3 cell lines, 1/26 cases<ref name=":9" />
|
|
|
|
|Unknown
|Unknown
|Unknown
|
|
|-
|-
|''AIM1''<ref name=":9" />
|''ATG5''<ref name=":9" />
|Tumor suppressor gene
|Tumor suppressor gene
|
|
|
|
|
|
|Unknown
|Unknown
|Unknown
|
|
|-
|''AIM1''<ref name=":9" />
|Tumor suppressor gene
|Methylated in NK-92, HANK1, NK-YS, SNK-1, YT cell lines; Mutated in in SNK-1 and SNK-6 cell lines<ref name=":9" />
|
|
|
|
|Unknown
|Unknown
|Unknown
|
|
|-
|-
|''FOXO3''<ref name=":9" /><ref name=":7" />
|''FOXO3''<ref name=":9" /><ref name=":7" />
|Tumor suppressor gene
|Tumor suppressor gene
|Mutated in 2/26 NKTCL and 1/9 ANKL<ref name=":9" />
|
|
|
|
|
|Unknown
|
|Unknown
|
|Unknown
|
|
|
|-
|-
|''HACE1''<ref name=":9" /><ref name=":13">{{Cite journal|last=Huang|first=Yenlin|last2=de Reyniès|first2=Aurélien|last3=de Leval|first3=Laurence|last4=Ghazi|first4=Bouchra|last5=Martin-Garcia|first5=Nadine|last6=Travert|first6=Marion|last7=Bosq|first7=Jacques|last8=Brière|first8=Josette|last9=Petit|first9=Barbara|date=2010-02-11|title=Gene expression profiling identifies emerging oncogenic pathways operating in extranodal NK/T-cell lymphoma, nasal type|url=https://pubmed.ncbi.nlm.nih.gov/19965620|journal=Blood|volume=115|issue=6|pages=1226–1237|doi=10.1182/blood-2009-05-221275|issn=1528-0020|pmc=2826234|pmid=19965620}}</ref>
|''HACE1''<ref name=":9" /><ref name=":13">{{Cite journal|last=Huang|first=Yenlin|last2=de Reyniès|first2=Aurélien|last3=de Leval|first3=Laurence|last4=Ghazi|first4=Bouchra|last5=Martin-Garcia|first5=Nadine|last6=Travert|first6=Marion|last7=Bosq|first7=Jacques|last8=Brière|first8=Josette|last9=Petit|first9=Barbara|date=2010-02-11|title=Gene expression profiling identifies emerging oncogenic pathways operating in extranodal NK/T-cell lymphoma, nasal type|url=https://pubmed.ncbi.nlm.nih.gov/19965620|journal=Blood|volume=115|issue=6|pages=1226–1237|doi=10.1182/blood-2009-05-221275|issn=1528-0020|pmc=2826234|pmid=19965620}}</ref>
|Tumor suppressor gene
|Tumor suppressor gene
|Mutated in 6/9 (67%) cell lines and 5/15 (33%) primary tumors<ref>{{Cite journal|last=Küçük|first=Can|last2=Hu|first2=Xiaozhou|last3=Iqbal|first3=Javeed|last4=Gaulard|first4=Philippe|last5=Klinkebiel|first5=David|last6=Cornish|first6=Adam|last7=Dave|first7=Bhavana J.|last8=Chan|first8=Wing C.|date=2013-01|title=HACE1 is a tumor suppressor gene candidate in natural killer cell neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/23142381|journal=The American Journal of Pathology|volume=182|issue=1|pages=49–55|doi=10.1016/j.ajpath.2012.09.012|issn=1525-2191|pmc=3532710|pmid=23142381}}</ref>
|
|
|
|
|
|Unknown
|
|Unknown
|
|Unknown
|
|
|
|}
|}
Line 350: Line 466:


==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==
[https://ashpublications.org/blood/article/115/6/1226/26917/Gene-expression-profiling-identifies-emerging Huang, ''et al''] described deregulation of several signaling pathways in NK T-cell lymphoma, main ones listed below<ref name=":13" />. A review by [https://jhoonline.biomedcentral.com/articles/10.1186/s13045-019-0716-7 De Mel, ''et al''], also outlines key molecular pathways involved in the pathogenesis of ENKTL<ref>{{Cite journal|last=de Mel|first=Sanjay|last2=Hue|first2=Susan Swee-Shan|last3=Jeyasekharan|first3=Anand D.|last4=Chng|first4=Wee-Joo|last5=Ng|first5=Siok-Bian|date=2019-04-02|title=Molecular pathogenic pathways in extranodal NK/T cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/30935402|journal=Journal of Hematology & Oncology|volume=12|issue=1|pages=33|doi=10.1186/s13045-019-0716-7|issn=1756-8722|pmc=6444858|pmid=30935402}}</ref>.
[https://ashpublications.org/blood/article/115/6/1226/26917/Gene-expression-profiling-identifies-emerging Huang, ''et al''] described deregulation of several signaling pathways in NK T-cell lymphoma, main ones listed below<ref name=":13" />. A review by [https://jhoonline.biomedcentral.com/articles/10.1186/s13045-019-0716-7 De Mel, ''et al''], also outlines key molecular pathways involved in the pathogenesis of ENKTL<ref name=":15">{{Cite journal|last=de Mel|first=Sanjay|last2=Hue|first2=Susan Swee-Shan|last3=Jeyasekharan|first3=Anand D.|last4=Chng|first4=Wee-Joo|last5=Ng|first5=Siok-Bian|date=2019-04-02|title=Molecular pathogenic pathways in extranodal NK/T cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/30935402|journal=Journal of Hematology & Oncology|volume=12|issue=1|pages=33|doi=10.1186/s13045-019-0716-7|issn=1756-8722|pmc=6444858|pmid=30935402}}</ref>.
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|''JAK3'', ''STAT3'', and ''STAT5B''; Activating mutations
|''JAK3'', ''STAT3'', and ''STAT5B''; Activating mutations<ref name=":13" /><ref name=":15" />
|JAK/STAT pathway
|JAK/STAT pathway
|Increased cell growth and proliferation
|Increased cell growth and proliferation
|-
|-
|''MYC, RUNX3''
|''MYC, RUNX3''<ref name=":15" />
|MYC
|MYC
|Increased cell proliferation and survival
|Increased cell proliferation and survival
|-
|-
|''AKT'' and related genes
|''AKT'' and related genes<ref name=":13" />
|AKT pathway
|AKT pathway
|Increased cell growth, proliferation and survival
|Increased cell growth, proliferation and survival
|-
|-
|NF-κB related genes
|NF-κB related genes<ref name=":13" /><ref name=":15" />
|NF-κB pathway
|NF-κB pathway
|Increased cell proliferation
|Increased cell proliferation
|-
|-
|''PDGFRA''
|''PDGFRA''<ref name=":13" /><ref name=":15" />
|PDGF pathway
|PDGF pathway
|Increased cell proliferation and survival
|Increased cell proliferation and survival
|-
|-
|''NOTCH1''
|''NOTCH1''<ref name=":15" />
|NOTCH1 pathway
|NOTCH1 pathway
|Increased cell proliferation
|Increased cell proliferation
|-
|-
|AURKA
|AURKA<ref name=":15" />
|Aurora kinase pathway<ref name=":12" />
|Aurora kinase pathway<ref name=":12" />
|Increased cell proliferation and cell cycle dysregulation
|Increased cell proliferation and cell cycle dysregulation
Line 394: Line 510:
==Additional Information==
==Additional Information==


N/A
This disease is <u>defined/characterized</u> as detailed below:
 
*Lymphoma of NK or T-cell lineage strongly associated with Epstein-Barr virus<ref name=":6" />. The lineage (NK or T-cell) has no clinical significance<ref name=":16" />.
*Divided into nasal and non-nasal types, the latter most often occurring in the skin and intestinal tract<ref name=":5" /><ref name=":6" />.
*It is a destructive angiocentric disease characterized by vascular destruction and necrosis<ref name=":17" />.
 
*Differential diagnosis: sinonasal carcinomas and other lymphomas of the nasal cavity, such as diffuse large B-cell lymphoma<ref name=":18" />.
 
The <u>epidemiology/prevalence</u> of this disease is detailed below:
 
*Most prevalent in East Asia and Latin America.
*Represents less than 1% of non-Hodgkin lymphomas in the United States
**Highest incidence among Asian Pacific Islanders and Hispanic populations<ref name=":19" />.
 
The <u>clinical features</u> of this disease are detailed below:
 
Signs and symptoms - Nasal mass, nasal obstruction, nasal bleeding; Hoarseness, dysphagia, halitosis, airway obstruction, dysphonia; Abdominal pain, GI bleeding, bowel perforation<ref name=":0" />; B symptoms (fever, weight loss, night sweats) associated with higher clinical stage<ref name=":20" />
 
Laboratory findings - No specific findings; Cytopenias
 
The <u>sites of involvement</u> of this disease are detailed below:
 
*Most are nasal type involving the upper aerodigestive tract
*Extranasal type may involve skin, testis, and gastrointestinal tract<ref name=":0" />.
*Bone marrow involvement is uncommon<ref name=":21" />.
 
The <u>morphologic features</u> of this disease are detailed below:
 
*Diffuse infiltrate composed of admixture of small, medium, or large and anaplastic cells.
*Cells have irregularly folded nuclei and moderate pale cytoplasm.
*Loss of mucosal glands.
*Angiocentric and angiodestructive growth pattern with coagulative necrosis.
*Usually see apoptotic cells and mitotic figures
 
Pitfalls:
 
*Mucosal ulceration and superimposed inflammation can mimic an inflammatory process, particularly in less aggressive cases<ref name=":22" />.
*Pseudoepitheliomatous hyperplasia of the overlying mucosal epithelium can mimic squamous cell carcinoma<ref name=":23" /><ref name=":24" />.
 
The <u>immunophenotype</u> of this disease is detailed below:
 
Positive (universal) - EBER / EBV
 
Positive (majority) - cytoplasmic CD3ε, CD2, CD56, granzyme B, and TIA-1
 
Positive (subset) - TCR αβ/γδ, HLA-DR, CD25, pSTAT3, CXCL13, IRF4/MUM1, CD16, Fas, FasL, MATK, CD30<ref name=":25" /><ref name=":26" /><ref name=":27" /><ref name=":28" /><ref name=":29" /><ref name=":30" /><ref name=":31" />
 
Negative (universal) - CD4, CD8
 
Negative (subset) - Surface CD3 (subset of T-cell lineage)<ref name=":0" />


==Links==
==Links==
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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'': “Extranodal NK/T-cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Extranodal_NK/T-cell_lymphoma</nowiki>.
<nowiki>*</nowiki>''Citation of this Page'': “Extranodal NK/T-cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Extranodal_NK/T-cell_lymphoma</nowiki>.
[[Category:HAEM5]]
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:DISEASE]]
[[Category:Diseases E]]
[[Category:Diseases E]]
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