Compendium of Cancer Genome Aberrations

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

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{{DISPLAYTITLE:Extranodal NK/T-cell lymphoma}}
{{DISPLAYTITLE:Extranodal NK/T-cell lymphoma}}
 
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
 
{{Under Construction}}
 
<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples). Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])</span>


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


Teodora Popa, MD, Queen's University
Ian King, PhD, FACMG


Amanda Xu, MD/MSc, Queen's University
Maryam Mehdipour Dalivand, MD


Put your text here<span style="color:#0070C0"> (''Name and affiliation; example:'' Jane Smith, PhD, Institute of Genomics) </span>
==WHO Classification of Disease==


__TOC__
{| class="wikitable"
 
!Structure
==Cancer Category / Type==
!Disease
 
|-
Mature T-cell and NK-cell neoplasms
|Book
 
|Haematolymphoid Tumours (5th ed.)
==Cancer Sub-Classification / Subtype==
|-
 
|Category
EBV-positive T-cell and NK-cell neoplasms  
|T-cell and NK-cell lymphoid proliferations and lymphomas
 
|-
==Definition / Description of Disease==
|Family
 
|Mature T-cell and NK-cell neoplasms
Extranodal NK/T-cell lymphoma is a distinct entity in the [https://tumourclassification.iarc.who.int/chaptercontent/63/258 5th edition World Health Organization (WHO) classification system]. It is referred to as "extranodal NK/T-cell lymphoma, nasal type" in the 2016 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues revised 4th edition<ref>_____, 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_______.</ref>.
|-
|Type
|EBV-positive NK-cell and T-cell lymphomas
|-
|Subtype(s)
|Extranodal NK/T-cell lymphoma
|}
==Related Terminology==


<nowiki>***</nowiki>Amanda, we do not have the revised 4th edition in our resident office... could you please check the page numbers and update the reference with the correct author and page numbers? thanks!
Put your text here <span style="color:#0070C0">(''Instructions: Brief description of approximately one paragraph - include disease context relative to other WHO classification categories referring to the specific WHO book pages, diagnostic criteria if applicable, and differential diagnosis if applicable'') </span>
==Synonyms / Terminology==
Extranodal NK/T-cell lymphoma, nasal type; EBV-positive extranodal NK/T-cell lymphoma; angiocentric lymphoma (historical); lethal midline granuloma (historical)
==Epidemiology / Prevalence==
Put your text here
==Clinical Features==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
{| class="wikitable"
{| class="wikitable"
|'''Signs and Symptoms'''
|Acceptable
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
|Extranodal NK/T-cell lymphoma, nasal type; EBV-positive extranodal NK/T-cell lymphoma
 
EXAMPLE B-symptoms (weight loss, fever, night sweats)
 
EXAMPLE Fatigue
 
EXAMPLE Lymphadenopathy (uncommon)
|-
|-
|'''Laboratory Findings'''
|Not Recommended
|EXAMPLE Cytopenias
|Angiocentric lymphoma; lethal midline granuloma
 
EXAMPLE Lymphocytosis (low level)
|}
|}


==Sites of Involvement==
==Gene Rearrangements==
 
Put your text here <span style="color:#0070C0">(''Instruction: Indicate physical sites; Example: nodal, extranodal, bone marrow'') </span>
 
==Morphologic Features==
 
Put your text here
 
==Immunophenotype==
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
 
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Finding!!Marker
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|Positive (universal)||EXAMPLE CD1
|CTLA4-CD28
|-
|CTLA4-CD28
|Positive (subset)||EXAMPLE CD2
|This fusion promotes tumor cell growth and survival by redirecting immune checkpoint signals<ref>{{Cite journal|last=Yoo|first=Hae Yong|last2=Kim|first2=Pora|last3=Kim|first3=Won Seog|last4=Lee|first4=Seung Ho|last5=Kim|first5=Sangok|last6=Kang|first6=So Young|last7=Jang|first7=Hye Yoon|last8=Lee|first8=Jong-Eun|last9=Kim|first9=Jaesang|date=2016-06-01|title=Frequent CTLA4-CD28 gene fusion in diverse types of T-cell lymphoma|url=https://haematologica.org/article/view/7742|journal=Haematologica|language=en|volume=101|issue=6|pages=757–763|doi=10.3324/haematol.2015.139253|issn=1592-8721|pmc=5013939|pmid=26819049}}</ref>
|-
|Chromosome 2q33
|Negative (universal)||EXAMPLE CD3
|29%
|-
|T: Therapeutically targetable through blockade of the CTLA4/CD28 pathway or its downstream signaling.
|Negative (subset)||EXAMPLE CD4
|No
|In extranodal NK/T-cell lymphoma, the '''CTLA4–CD28 fusion''' identifies a molecular subset in which aberrant CD28 costimulatory signaling likely contributes to tumor growth and survival. Clinically, this suggests potential '''therapeutic vulnerability to agents targeting the CTLA4/CD28 axis or downstream signaling pathways''', although it is not specific enough to be a primary diagnostic marker and currently serves more as a '''biologic and potential predictive marker''' rather than a routine clinical test.
|}
|}


==Chromosomal Rearrangements (Gene Fusions)==
==Individual Region Genomic Gain/Loss/LOH==
 
Put your text here and fill in the table
 
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
!Diagnostic Significance (Yes, No or Unknown)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Prognostic Significance (Yes, No or Unknown)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Therapeutic Significance (Yes, No or Unknown)
!Clinical Relevance Details/Other Notes
!Notes
|-
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
|6
EXAMPLE 30% (add reference)
|Loss
|Yes
|~2.6 Mb interval within 6q21–q25<ref>{{Cite journal|last=De Mel|first=Sanjay|last2=Soon|first2=Gwyneth Shook-Ting|last3=Mok|first3=Yingting|last4=Chung|first4=Tae-Hoon|last5=Jeyasekharan|first5=Anand D.|last6=Chng|first6=Wee-Joo|last7=Ng|first7=Siok-Bian|date=2018-06-30|title=The Genomics and Molecular Biology of Natural Killer/T-Cell Lymphoma: Opportunities for Translation|url=https://doi.org/10.3390/ijms19071931|journal=International Journal of Molecular Sciences|volume=19|issue=7|pages=1931|doi=10.3390/ijms19071931|issn=1422-0067}}</ref>
|This locus harbors multiple candidate genes including ATG5, AIM1, PRDM1, PTPRK, HACE1 and FOXO3<ref name=":32">{{Cite journal|last=Iqbal|first=J.|last2=Kucuk|first2=C.|last3=Deleeuw|first3=R. J.|last4=Srivastava|first4=G.|last5=Tam|first5=W.|last6=Geng|first6=H.|last7=Klinkebiel|first7=D.|last8=Christman|first8=J. K.|last9=Patel|first9=K.|date=2009-06|title=Genomic analyses reveal global functional alterations that promote tumor growth and novel tumor suppressor genes in natural killer-cell malignancies|url=https://pubmed.ncbi.nlm.nih.gov/19194464|journal=Leukemia|volume=23|issue=6|pages=1139–1151|doi=10.1038/leu.2009.3|issn=1476-5551|pmid=19194464}}</ref><ref name=":7">{{Cite journal|last=Karube|first=Kennosuke|last2=Nakagawa|first2=Masao|last3=Tsuzuki|first3=Shinobu|last4=Takeuchi|first4=Ichiro|last5=Honma|first5=Keiichiro|last6=Nakashima|first6=Yasuhiro|last7=Shimizu|first7=Norio|last8=Ko|first8=Young-Hyeh|last9=Morishima|first9=Yasuo|date=2011-09-22|title=Identification of FOXO3 and PRDM1 as tumor-suppressor gene candidates in NK-cell neoplasms by genomic and functional analyses|url=https://pubmed.ncbi.nlm.nih.gov/21690554|journal=Blood|volume=118|issue=12|pages=3195–3204|doi=10.1182/blood-2011-04-346890|issn=1528-0020|pmid=21690554}}</ref><ref name=":1">{{Cite journal|last=Chen|first=Yun-Wen|last2=Guo|first2=Tianhuan|last3=Shen|first3=Lijun|last4=Wong|first4=Kai-Yau|last5=Tao|first5=Qian|last6=Choi|first6=William W. L.|last7=Au-Yeung|first7=Rex K. H.|last8=Chan|first8=Yuen-Piu|last9=Wong|first9=Michelle L. Y.|date=2015-03-05|title=Receptor-type tyrosine-protein phosphatase κ directly targets STAT3 activation for tumor suppression in nasal NK/T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/25612622|journal=Blood|volume=125|issue=10|pages=1589–1600|doi=10.1182/blood-2014-07-588970|issn=1528-0020|pmid=25612622}}</ref>
|D: Chromosome 6q loss is a recurrent abnormality in ENKTL that provides supportive molecular evidence of neoplasia and helps distinguish ENKTL from other T/NK-cell proliferations, but it is not sufficient for a standalone diagnosis.<ref>{{Cite journal|last=Liang|first=Li|last2=Zhang|first2=Zhang|last3=Wang|first3=Ying|last4=Nong|first4=Lin|last5=Zheng|first5=Yalin|last6=Qu|first6=Linlin|last7=Zhang|first7=Bo|last8=Li|first8=Ting|date=2015|title=The Genetic Deletion of 6q21 and PRDM1 and Clinical Implications in Extranodal NK/T Cell Lymphoma, Nasal Type|url=https://pubmed.ncbi.nlm.nih.gov/26221594|journal=BioMed Research International|volume=2015|pages=435423|doi=10.1155/2015/435423|issn=2314-6141|pmc=4499638|pmid=26221594}}</ref>
P: Loss of chromosome 6q in ENKTL is associated with deletion of key tumor suppressor genes and correlates with aggressive disease features and poorer survival, making it an adverse prognostic marker.
|No
|No
|Yes
|Chromosome 6q loss in ENKTL is a recurrent molecular abnormality that supports diagnosis, indicates aggressive clinical behavior. Loss of chromosome 6q in ENKTL is not directly targetable but highlights deletion of tumor suppressor genes and activation of downstream pathways, such as JAK/STAT and NF-κB. This suggests potential susceptibility to pathway-specific therapies in high-risk patients. <ref>{{Cite journal|last=Costa|first=Renata de Oliveira|last2=Pereira|first2=Juliana|last3=Lage|first3=Luís Alberto de Pádua Covas|last4=Baiocchi|first4=Otávio César Guimarães|date=2023-07-17|title=Extranodal NK-/T-cell lymphoma, nasal type: what advances have been made in the last decade?|url=https://www.frontiersin.org/articles/10.3389/fonc.2023.1175545/full|journal=Frontiers in Oncology|volume=13|doi=10.3389/fonc.2023.1175545|issn=2234-943X}}</ref><ref>{{Cite journal|last=Tse|first=Eric|last2=Kwong|first2=Yok-Lam|date=2017-12|title=The diagnosis and management of NK/T-cell lymphomas|url=http://jhoonline.biomedcentral.com/articles/10.1186/s13045-017-0452-9|journal=Journal of Hematology & Oncology|language=en|volume=10|issue=1|doi=10.1186/s13045-017-0452-9|issn=1756-8722}}</ref>
|EXAMPLE
|}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>.
 
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
|}
==Individual Region Genomic Gain / Loss / LOH==
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span>


==Characteristic Chromosomal or Other Global Mutational Patterns==
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
Line 122: Line 85:
!Notes
!Notes
|-
|-
|EXAMPLE
|Isochromosome 6p<ref>{{Cite journal|last=Tien|first=H. F.|last2=Su|first2=I. J.|last3=Tang|first3=J. L.|last4=Liu|first4=M. C.|last5=Lee|first5=F. Y.|last6=Chen|first6=Y. C.|last7=Chuang|first7=S. M.|date=1997-06|title=Clonal chromosomal abnormalities as direct evidence for clonality in nasal T/natural killer cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/9207410|journal=British Journal of Haematology|volume=97|issue=3|pages=621–625|doi=10.1046/j.1365-2141.1997.752711.x|issn=0007-1048|pmid=9207410}}</ref>
|Unknown
|Yes, isochromosome (6p) leads to '''loss of 6q tumor suppressor genes''' (''PRDM1, FOXO3, HACE1'') and '''gain of 6p genes''', which may enhance proliferation.This dual effect is thought to contribute to '''more aggressive tumor biology''' compared with simple 6q deletions.<ref>{{Cite journal|last=Tse|first=Eric|last2=Kwong|first2=Yok-Lam|date=2017-12|title=The diagnosis and management of NK/T-cell lymphomas|url=http://jhoonline.biomedcentral.com/articles/10.1186/s13045-017-0452-9|journal=Journal of Hematology & Oncology|language=en|volume=10|issue=1|doi=10.1186/s13045-017-0452-9|issn=1756-8722}}</ref><ref>{{Cite journal|last=De Mel|first=Sanjay|last2=Soon|first2=Gwyneth Shook-Ting|last3=Mok|first3=Yingting|last4=Chung|first4=Tae-Hoon|last5=Jeyasekharan|first5=Anand D.|last6=Chng|first6=Wee-Joo|last7=Ng|first7=Siok-Bian|date=2018-06-30|title=The Genomics and Molecular Biology of Natural Killer/T-Cell Lymphoma: Opportunities for Translation|url=https://www.mdpi.com/1422-0067/19/7/1931|journal=International Journal of Molecular Sciences|language=en|volume=19|issue=7|pages=1931|doi=10.3390/ijms19071931|issn=1422-0067}}</ref>
|Unknown
|N/A
|-
|Isochromosome 7q<ref>{{Cite journal|last=Feldman|first=Andrew L.|last2=Law|first2=Mark|last3=Grogg|first3=Karen L.|last4=Thorland|first4=Erik C.|last5=Fink|first5=Stephanie|last6=Kurtin|first6=Paul J.|last7=Macon|first7=William R.|last8=Remstein|first8=Ellen D.|last9=Dogan|first9=Ahmet|date=2008-08|title=Incidence of TCR and TCL1 gene translocations and isochromosome 7q in peripheral T-cell lymphomas using fluorescence in situ hybridization|url=https://pubmed.ncbi.nlm.nih.gov/18628085|journal=American Journal of Clinical Pathology|volume=130|issue=2|pages=178–185|doi=10.1309/PNXUKA1CFJMVGCN1|issn=0002-9173|pmc=3625137|pmid=18628085}}</ref>
|Unknown
|Unknown
|Unknown
|N/A
|}


7
==Gene Mutations (SNV/INDEL)==
|EXAMPLE Loss
{| class="wikitable sortable"
|EXAMPLE
|-
 
!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
chr7:1- 159,335,973 [hg38]
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
|EXAMPLE
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  
 
!Established Clinical Significance Per Guidelines - Yes or No (Source)
chr7
!Clinical Relevance Details/Other Notes
|Yes
|-
|Yes
|JAK3
|Activating mutations
|Oncogene
|Common<ref name=":10" />
|T
|No
|Pan-JAK and selective JAK3 inhibitors have been suggested as potential therapeutic options<ref name=":10">{{Cite journal|last=Koo|first=Ghee Chong|last2=Tan|first2=Soo Yong|last3=Tang|first3=Tiffany|last4=Poon|first4=Song Ling|last5=Allen|first5=George E.|last6=Tan|first6=Leonard|last7=Chong|first7=Soo Ching|last8=Ong|first8=Whee Sze|last9=Tay|first9=Kevin|date=2012-07|title=Janus kinase 3-activating mutations identified in natural killer/T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/22705984|journal=Cancer Discovery|volume=2|issue=7|pages=591–597|doi=10.1158/2159-8290.CD-12-0028|issn=2159-8290|pmid=22705984}}</ref><ref name=":33">{{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.
|-
|''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
|Recurrent<ref name=":3" /><ref name=":4" />
|T
|No
|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>.
|-
|''TP53''<ref name=":2" />
|
|Tumor suppressor gene
|Common<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>
|P
|No
|Associated with advanced stage disease
|-
|''STAT5B''<ref name=":2" /><ref name=":3" />
|
|Oncogene
|Recurrent<ref name=":3" />
|No
|No
|n/a
|-
|''PTPRK''<ref name=":1" />
|
|Other (acts on JAK/STAT pathway; underexpression leads to STAT3 activation<ref name=":1" />)
|
|No
|No
|n/a
|-
|''MYC''<ref name=":12">{{Cite journal|last=Ng|first=Siok-Bian|last2=Selvarajan|first2=Viknesvaran|last3=Huang|first3=Gaofeng|last4=Zhou|first4=Jianbiao|last5=Feldman|first5=Andrew L.|last6=Law|first6=Mark|last7=Kwong|first7=Yok-Lam|last8=Shimizu|first8=Norio|last9=Kagami|first9=Yoshitoyo|date=2011-03|title=Activated oncogenic pathways and therapeutic targets in extranodal nasal-type NK/T cell lymphoma revealed by gene expression profiling|url=https://pubmed.ncbi.nlm.nih.gov/21294123|journal=The Journal of Pathology|volume=223|issue=4|pages=496–510|doi=10.1002/path.2823|issn=1096-9896|pmid=21294123}}</ref>
|
|Oncogene
|
|No
|No
|n/a
|-
|''PDGFRA''<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>
|
|Oncogene
|
|No
|No
|n/a
|-
|''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
|
|No
|No
|n/a
|-
|''RAS/KRAS/HRAS''
|
|Oncogene
|Rare<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>
|No
|No
|n/a
|-
|''FAS''
|
|Oncogene
|Common<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 name=":34">{{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>
|No
|No
|n/a
|-
|''KIT''
|
|Oncogene
|Common<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>
|No
|No
|n/a
|-
|''CTNNB1''
|
|Oncogene
|Common<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>
|No
|No
|n/a
|-
|''DDX3X''<ref name=":2" />
|
|Epigenetic modifier (RNA helicase)
|Recurrent<ref name=":2" />
|No
|No
|n/a
|-
|''KMT2D (MLL2)''<ref name=":2" />
|
|Epigenetic modifier
|Common<ref name=":4" />
|No
|No
|n/a
|-
|''ARID1A''<ref name=":2" />
|
|Epigenetic modifier
|
|No
|No
|n/a
|-
|''EP300''<ref name=":2" />
|
|Epigenetic modifier
|
|No
|No
|n/a
|-
|''ASXL3''<ref name=":2" />
|
|Epigenetic modifier
|
|No
|No
|No
|EXAMPLE
|n/a
 
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
|-
|-
|EXAMPLE
|''BCOR''<ref name=":4" />
 
|
8
|Epigenetic modifier
|EXAMPLE Gain
|38.2%<ref name=":4" />
|EXAMPLE
 
chr8:1-145,138,636 [hg38]
|EXAMPLE
 
chr8
|No
|No
|No
|No
|n/a
|-
|''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
|
|No
|No
|EXAMPLE
|No
 
|n/a
Common recurrent secondary finding for t(8;21) (add reference).
|}
==Characteristic Chromosomal Patterns==
 
Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis'')</span>
 
{| class="wikitable sortable"
|-
|-
!Chromosomal Pattern
|''MGA''<ref name=":2" />
!Diagnostic Significance (Yes, No or Unknown)
|
!Prognostic Significance (Yes, No or Unknown)
|Tumor suppressor gene
!Therapeutic Significance (Yes, No or Unknown)
|
!Notes
|No
|No
|n/a
|-
|-
|EXAMPLE
|''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>
 
|
Co-deletion of 1p and 18q
|Tumor suppressor gene
|Yes
|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" />
|No
|No
|No
|No
|EXAMPLE:
|n/a
 
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|}
==Gene Mutations (SNV / INDEL)==
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.'') </span>
 
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC / TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
|''ATG5''<ref name=":9" />
!'''Diagnostic Significance (Yes, No or Unknown)'''
|
!Prognostic Significance (Yes, No or Unknown)
|Tumor suppressor gene
!Therapeutic Significance (Yes, No or Unknown)
|
!Notes
|No
|No
|n/a
|-
|-
|EXAMPLE: TP53; Variable LOF mutations
|''AIM1''<ref name=":9" />
 
EXAMPLE:
 
EGFR; Exon 20 mutations
 
EXAMPLE: BRAF; Activating mutations
|EXAMPLE: TSG
|EXAMPLE: 20% (COSMIC)
 
EXAMPLE: 30% (add Reference)
|EXAMPLE: IDH1 R123H
|EXAMPLE: EGFR amplification
|
|
|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" />
|No
|No
|n/a
|-
|''FOXO3''<ref name=":9" /><ref name=":7" />
|
|
|Tumor suppressor gene
|Mutated in 2/26 NKTCL and 1/9 ANKL<ref name=":9" />
|No
|No
|n/a
|-
|''HACE1''<ref name=":9" /><ref name=":13" />
|
|
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
|Tumor suppressor gene
<br />
|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>
|No
|No
|n/a
|}
|}
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
Line 213: Line 311:
==Epigenomic Alterations==
==Epigenomic Alterations==


Put your text here
N/A


==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 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>.
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
|''JAK3'', ''STAT3'', and ''STAT5B''; Activating mutations<ref name=":13" /><ref name=":15" />
|EXAMPLE: MAPK signaling
|JAK/STAT pathway
|EXAMPLE: Increased cell growth and proliferation
|Increased cell growth and proliferation
|-
|''MYC, RUNX3''<ref name=":15" />
|MYC
|Increased cell proliferation and survival
|-
|''AKT'' and related genes<ref name=":13" />
|AKT pathway
|Increased cell growth, proliferation and survival
|-
|NF-κB related genes<ref name=":13" /><ref name=":15" />
|NF-κB pathway
|Increased cell proliferation
|-
|''PDGFRA''<ref name=":13" /><ref name=":15" />
|PDGF pathway
|Increased cell proliferation and survival
|-
|-
|EXAMPLE: CDKN2A; Inactivating mutations
|''NOTCH1''<ref name=":15" />
|EXAMPLE: Cell cycle regulation
|NOTCH1 pathway
|EXAMPLE: Unregulated cell division
|Increased cell proliferation
|-
|-
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
|AURKA<ref name=":15" />
|EXAMPLE:  Histone modification, chromatin remodeling
|Aurora kinase pathway<ref name=":12" />
|EXAMPLE:  Abnormal gene expression program
|Increased cell proliferation and cell cycle dysregulation
|}
|}
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==


Put your text here
*Select cases may require TCR gene rearrangement studies; otherwise, not routinely performed.
*EBV PCR testing may be used for disease monitoring


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


Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
N/A


==Additional Information==
==Additional Information==
[[File:Extranodal NK T-cell lymphoma, nasal type.png|thumb|Extranodal NK T-cell lymphoma, nasal type (HPS). Angiocentric and angiodestructive growth pattern.]]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">{{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" />.
*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>.


Put your text here
*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>.
 
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">{{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>.
 
The <u>clinical features</u> of this disease are detailed below: [[File:Extranodal NK T-cell lymphoma, nasal type.vsi(17.8X) snapshot.png|thumb|Extranodal NK T-cell lymphoma, nasal type (HPS). Angiocentric and angiodestructive growth pattern.]]
 
Signs and symptoms - Nasal mass, nasal obstruction, nasal bleeding; Hoarseness, dysphagia, halitosis, airway obstruction, dysphonia; 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 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>
 
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">{{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>.
 
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[[File:IHC NKTCL.png|thumb|Extranodal NK T-cell lymphoma stained with CD2 (top left), CD56 (red chromogen; top right), EBER in-situ hybridization (bottom left) and TIA1 (bottom right).]]
 
The pitfalls can include:
 
*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 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>.
 
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">{{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 (subset) - Surface CD3 (subset of T-cell lineage)<ref name=":0" />


==Links==
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==Notes==
 
<nowiki>*</nowiki>''Citation of this Page'': King I, Dalivand MM. “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>.


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#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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<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>.
Prior Author(s): Teodora Popa, MD, Amanda Xu, MD 
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