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

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==Definition / Description of Disease==
 
==Definition / Description of Disease==
  
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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>.
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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>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>.
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<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!'''
 
  
 
Extranodal NK/T-cell lymphoma (ENKTL) is a lymphoma of NK or T-cell lineage strongly associated with Epstein-Barr virus (citation needed)
 
Extranodal NK/T-cell lymphoma (ENKTL) is a lymphoma of NK or T-cell lineage strongly associated with Epstein-Barr virus (citation needed)
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The lineage (NK or T-cell) has no clinical significance (citation needed)
 
  
 
ENKTL is a destructive angiocentric disease characterized by vascular destruction and necrosis (citation needed)
 
ENKTL is a destructive angiocentric disease characterized by vascular destruction and necrosis (citation needed)
  
 
It can be clinically divided into nasal and non-nasal types (citation needed)
 
It can be clinically divided into nasal and non-nasal types (citation needed)
 +
 +
The lineage (NK or T-cell) has no clinical significance (citation needed)
  
 
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>
 
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>
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|Unknown
 
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|This locus harbours multiple candidate tumour suppressor genes including ''ATG5'', ''AIM1'', ''PRDM1'', ''PTPRK'', ''HACE1'', and ''FOXO3''<ref>{{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>{{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>{{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>.
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|This locus harbours multiple candidate tumour suppressor genes including ''ATG5'', ''AIM1'', ''PRDM1'', ''PTPRK'', ''HACE1'', and ''FOXO3''<ref>{{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>{{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>.
 
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|''JAK3''<ref>{{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>
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|''JAK3''<ref>{{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>{{Cite journal|last=Bouchekioua|first=A.|last2=Scourzic|first2=L.|last3=de Wever|first3=O.|last4=Zhang|first4=Y.|last5=Cervera|first5=P.|last6=Aline-Fardin|first6=A.|last7=Mercher|first7=T.|last8=Gaulard|first8=P.|last9=Nyga|first9=R.|date=2014-02|title=JAK3 deregulation by activating mutations confers invasive growth advantage in extranodal nasal-type natural killer cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/23689514|journal=Leukemia|volume=28|issue=2|pages=338–348|doi=10.1038/leu.2013.157|issn=1476-5551|pmid=23689514}}</ref>
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|JAK3 inhibitor is a potential therapeutic option<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>
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|''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>
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|STAT3 inhibitor<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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|24-62%<ref>{{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>{{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>
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==Epigenomic Alterations==
 
==Epigenomic Alterations==
  
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Put your text here
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A 2015 study by Lee'', et al'' reported that histone modification-related genes accounted for 38.2% of 34 ENKTL samples by next-generation sequencing<ref name=":4" />.
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Similarly, a 2015 study by Lu, et al uncovered recurrent mutations in the RNA helicase gene DDX3X and other epigenetic modifiers including KMT2D (MLL2), ARID1A, EP300, and ASXL3<ref name=":2" />.
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* ''DDX3X'' (RNA helicase)
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* ''ARID1A''
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==Genes and Main Pathways Involved==
 
==Genes and Main Pathways Involved==
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==References==
 
==References==
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(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />
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'''EXAMPLE Book'''
 
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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.
 
  
 
==Notes==
 
==Notes==

Revision as of 15:26, 21 June 2024


Haematolymphoid Tumours (5th ed.)

(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use HUGO-approved gene names and symbols (italicized when appropriate), 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 Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)

Primary Author(s)*

Teodora Popa, MD, Queen's University

Amanda Xu, MD/MSc, Queen's University

Cancer Category / Type

Mature T-cell and NK-cell neoplasms

Cancer Sub-Classification / Subtype

EBV-positive T-cell and NK-cell neoplasms

Definition / Description of Disease

Extranodal NK/T-cell lymphoma is a distinct entity in the 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[1].

Extranodal NK/T-cell lymphoma (ENKTL) is a lymphoma of NK or T-cell lineage strongly associated with Epstein-Barr virus (citation needed)

ENKTL is a destructive angiocentric disease characterized by vascular destruction and necrosis (citation needed)

It can be clinically divided into nasal and non-nasal types (citation needed)

The lineage (NK or T-cell) has no clinical significance (citation needed)

Put your text here (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)

Synonyms / Terminology

Extranodal NK/T-cell lymphoma, nasal type; EBV-positive extranodal NK/T-cell lymphoma; angiocentric lymphoma (not recommended); lethal midline granuloma (historical)

Epidemiology / Prevalence

ENKTL is most prevalent in East Asia and Latin America. It represents less than 1% of non-Hodgkin lymphomas in the United States, with the highest incidence among Asian Pacific Islanders and Hispanic populations[2].

Clinical Features

Common clinical presentations of nasal-type ENKTL include nasal mass, obstruction, and bleeding. Patients with abdominal involvement may present with abdominal pain, gastrointestinal (GI) bleed, or perforation[3]. The presence of B symptoms is associated with higher clinical stage[4].

Signs and Symptoms Nasal mass, nasal obstruction, nasal bleeding

Hoarseness, dysphagia, halitosis, airway obstruction, dysphonia

Abdominal pain, GI bleeding, bowel perforation

B symptoms (fever, weight loss, night sweats)

Laboratory Findings No specific findings

Cytopenias

Sites of Involvement

Most cases of ENKTL are nasal type, meaning they involve the upper aerodigestive tract. Extranasal ENKTL may involve the skin, testis, and gastrointestinal tract[3]. Bone marrow involvement is uncommon[5].

Morphologic Features

  • Diffuse lymphomatous infiltrate composed of small, medium, or large and anaplastic cells (or a mix of small and large cells). The cells have irregularly folded nuclei and moderate pale cytoplasm.
  • Loss of mucosal glands.
  • Angiocentric and angiodestructive growth pattern.
  • Coagulative necrosis and apoptosis.
  • Mitotic figures.

Pitfalls:

  • Mucosal ulceration and superimposed inflammation can mimic an inflammatory process, particularly in less aggressive cases[6].
  • Pseudoepitheliomatous hyperplasia of the overlying mucosal epithelium can mimic squamous cell carcinoma[7][8].


***Amanda, do you know if we have any good cases we could scan and add photos of?

Immunophenotype

The majority of cases are positive for cytoplasmic CD3ε, CD2, granzyme B, and TIA-1. Most ENKTLs are of NK-lineage and express CD56. Cases of T-lineage express T-cell receptor (TCR) and show clonal TCR gene rearrangements. All cases are EBV positive by in situ hybridization for Epstein-Barr virus-encoded small RNA (EBER). Other markers that may be expressed include HLA-DR, CD25, pSTAT3, CXCL13, IRF4/MUM1, CD16, Fas, FasL, MATK, and CD30[9][10][11][12][13][14][15].

Finding Marker
Positive (universal) CD2, CD56, cytoplasmic CD3ε, cytotoxic markers (TIA-1, granzyme B, perforin)

EBER / EBV

Positive (subset) TCR αβ/γδ, HLA-DR, CD25, pSTAT3, CXCL13, IRF4/MUM1, CD16, Fas, FasL, MATK, CD30
Negative (universal) CD4, CD8
Negative (subset) Surface CD3 (subset of T-cell lineage)[3]

Chromosomal Rearrangements (Gene Fusions)

No specific chromosomal translocation has been identified in ENKTL.

Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
N/A N/A N/A N/A N/A N/A N/A N/A

Individual Region Genomic Gain / Loss / LOH

ENKTL shows recurring deletion at 6q21-25[16][17].

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[18][19][20][21][22].

Put your text here and fill in the table (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.)

Chr # Gain / Loss / Amp / LOH Minimal Region Genomic Coordinates [Genome Build] Minimal Region Cytoband Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
6 Loss 6q21-25 Unknown Unknown Unknown This locus harbours multiple candidate tumour suppressor genes including ATG5, AIM1, PRDM1, PTPRK, HACE1, and FOXO3[23][24][25].
EXAMPLE

8

EXAMPLE Gain EXAMPLE

chr8:1-145,138,636 [hg38]

EXAMPLE

chr8

No No No EXAMPLE

Common recurrent secondary finding for t(8;21) (add reference).

Characteristic Chromosomal Patterns

No characteristic chromosomal patterns have been identified in ENKTL.

Chromosomal Pattern Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
N/A N/A N/A N/A N/A

Gene Mutations (SNV / INDEL)

Put your text here and fill in the table (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.)

Gene; Genetic Alteration Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other) Prevalence (COSMIC / TCGA / Other) Concomitant Mutations Mutually Exclusive Mutations Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
JAK3[26][27] Oncogene JAK3 inhibitor is a potential therapeutic option[28]
STAT3[29][30][31] STAT3 inhibitor[32]
STAT5B[29][30]
PTPRK[25]
KIT[25]
CTNNB1[25]
TP53[29] Tumor suppressor gene 24-62%[33][34]
MGA
PRDM1
ATG5
AIM1
FOXO3
HACE1
RAS
EXAMPLE: TP53; Variable LOF mutations

EXAMPLE:

EGFR; Exon 20 mutations

EXAMPLE: BRAF; Activating mutations

EXAMPLE: TSG EXAMPLE: 20% (COSMIC)

EXAMPLE: 30% (add Reference)

EXAMPLE: IDH1 R123H EXAMPLE: EGFR amplification EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).


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.

Epigenomic Alterations

A 2015 study by Lee, et al reported that histone modification-related genes accounted for 38.2% of 34 ENKTL samples by next-generation sequencing[31].

Similarly, a 2015 study by Lu, et al uncovered recurrent mutations in the RNA helicase gene DDX3X and other epigenetic modifiers including KMT2D (MLL2), ARID1A, EP300, and ASXL3[29].

  • DDX3X (RNA helicase)
  • KMT2D/MLL2
  • ARID1A
  • EP300
  • ASXL3
  • BCOR

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Can include references in the table.)

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
EXAMPLE: BRAF and MAP2K1; Activating mutations EXAMPLE: MAPK signaling EXAMPLE: Increased cell growth and proliferation
EXAMPLE: CDKN2A; Inactivating mutations EXAMPLE: Cell cycle regulation EXAMPLE: Unregulated cell division
EXAMPLE:  KMT2C and ARID1A; Inactivating mutations EXAMPLE:  Histone modification, chromatin remodeling EXAMPLE:  Abnormal gene expression program

Genetic Diagnostic Testing Methods

Put your text here

Familial Forms

Put your text here (Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.)

Additional Information

Put your text here

Links

Put your text placeholder here (or anywhere appropriate on the page) and use the "Link" icon at the top of the page (Instructions: Once you have a text placeholder entered to which you want to add a link, highlight that text, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address including the "http://www." portion.)

References

  1. ↑ 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.
  2. ↑ Haverkos, Bradley M.; et al. (2016-12). "Extranodal NK/T-cell lymphoma, nasal type (ENKTL-NT): An update on epidemiology, clinical presentation, and natural history in North American and European cases". Current hematologic malignancy reports. 11 (6): 514–527. doi:10.1007/s11899-016-0355-9. ISSN 1558-8211. PMC 5199232. PMID 27778143. Check date values in: |date= (help)
  3. ↑ 3.0 3.1 3.2 Thida AM, Gohari P. Extranodal NK-Cell Lymphoma. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559207/
  4. ↑ Takahara, Miki; et al. (2021-06-25). "Extranodal NK/T-Cell Lymphoma, Nasal Type: Genetic, Biologic, and Clinical Aspects with a Central Focus on Epstein-Barr Virus Relation". Microorganisms. 9 (7): 1381. doi:10.3390/microorganisms9071381. ISSN 2076-2607. PMC 8304202 Check |pmc= value (help). PMID 34202088 Check |pmid= value (help).
  5. ↑ Wong, K. F.; et al. (2001-02). "Bone marrow involvement by nasal NK cell lymphoma at diagnosis is uncommon". American Journal of Clinical Pathology. 115 (2): 266–270. doi:10.1309/E5PR-6A9R-Q02N-8QVW. ISSN 0002-9173. PMID 11211616. Check date values in: |date= (help)
  6. ↑ 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). https://doi.org/10.1186/s13000-018-0765-1
  7. ↑ Ling, Yi-Hong; et al. (2015-09). "Pseudoepitheliomatous hyperplasia mimicking invasive squamous cell carcinoma in extranodal natural killer/T-cell lymphoma: a report of 34 cases". Histopathology. 67 (3): 404–409. doi:10.1111/his.12656. ISSN 1365-2559. PMID 25619876. Check date values in: |date= (help)
  8. ↑ Xiang, Chun-Xiang; et al. (2019-07). "Laryngeal Extranodal Nasal-type Natural Killer/T-cell Lymphoma: A Clinicopathologic Study of 31 Cases in China". The American Journal of Surgical Pathology. 43 (7): 995–1004. doi:10.1097/PAS.0000000000001266. ISSN 1532-0979. PMID 31045893. Check date values in: |date= (help)
  9. ↑ Li, Shaoying; et al. (2013-01). "Extranodal NK/T-cell lymphoma, nasal type: a report of 73 cases at MD Anderson Cancer Center". The American Journal of Surgical Pathology. 37 (1): 14–23. doi:10.1097/PAS.0b013e31826731b5. ISSN 1532-0979. PMID 23232851. Check date values in: |date= (help)
  10. ↑ Jhuang, Jie-Yang; et al. (2015-02). "Extranodal natural killer/T-cell lymphoma, nasal type in Taiwan: a relatively higher frequency of T-cell lineage and poor survival for extranasal tumors". Human Pathology. 46 (2): 313–321. doi:10.1016/j.humpath.2014.11.008. ISSN 1532-8392. PMID 25554090. Check date values in: |date= (help)
  11. ↑ Pongpruttipan, Tawatchai; et al. (2012-04). "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". The American Journal of Surgical Pathology. 36 (4): 481–499. doi:10.1097/PAS.0b013e31824433d8. ISSN 1532-0979. PMID 22314189. Check date values in: |date= (help)
  12. ↑ Jaffe, E. S.; et al. (1996-01). "Report of the Workshop on Nasal and Related Extranodal Angiocentric T/Natural Killer Cell Lymphomas. Definitions, differential diagnosis, and epidemiology". The American Journal of Surgical Pathology. 20 (1): 103–111. doi:10.1097/00000478-199601000-00012. ISSN 0147-5185. PMID 8540601. Check date values in: |date= (help)
  13. ↑ Ohshima, K.; et al. (1997-11). "Nasal T/NK cell lymphomas commonly express perforin and Fas ligand: important mediators of tissue damage". Histopathology. 31 (5): 444–450. doi:10.1046/j.1365-2559.1997.2880887.x. ISSN 0309-0167. PMID 9416485. Check date values in: |date= (help)
  14. ↑ Takata, Katsuyoshi; et al. (2015-01). "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". The American Journal of Surgical Pathology. 39 (1): 1–12. doi:10.1097/PAS.0000000000000312. ISSN 1532-0979. PMID 25188863. Check date values in: |date= (help)
  15. ↑ Kuo, Tseng-Tong; et al. (2004-10). "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". International Journal of Surgical Pathology. 12 (4): 375–387. doi:10.1177/106689690401200410. ISSN 1066-8969. PMID 15494863. Check date values in: |date= (help)
  16. ↑ Wong, K. F.; et al. (1997-09). "Identification of del(6)(q21q25) as a recurring chromosomal abnormality in putative NK cell lymphoma/leukaemia". British Journal of Haematology. 98 (4): 922–926. doi:10.1046/j.1365-2141.1997.3223139.x. ISSN 0007-1048. PMID 9326190. Check date values in: |date= (help)
  17. ↑ Ohshima, Koichi; et al. (2002-02). "Analysis of chromosome 6q deletion in EBV-associated NK cell leukaemia/lymphoma". Leukemia & Lymphoma. 43 (2): 293–300. doi:10.1080/10428190290006062. ISSN 1042-8194. PMID 11999560. Check date values in: |date= (help)
  18. ↑ Nakashima, Yasuhiro; et al. (2005-11). "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". Genes, Chromosomes & Cancer. 44 (3): 247–255. doi:10.1002/gcc.20245. ISSN 1045-2257. PMID 16049916. Check date values in: |date= (help)
  19. ↑ Siu, L. L.; et al. (2000-12). "Consistent patterns of allelic loss in natural killer cell lymphoma". The American Journal of Pathology. 157 (6): 1803–1809. doi:10.1016/S0002-9440(10)64818-3. ISSN 0002-9440. PMC 1885756. PMID 11106552. Check date values in: |date= (help)
  20. ↑ Siu, L. L.; et al. (1999-11). "Comparative genomic hybridization analysis of natural killer cell lymphoma/leukemia. Recognition of consistent patterns of genetic alterations". The American Journal of Pathology. 155 (5): 1419–1425. doi:10.1016/S0002-9440(10)65454-5. ISSN 0002-9440. PMC 1866965. PMID 10550295. Check date values in: |date= (help)
  21. ↑ Wong, K. F.; et al. (1999-07). "Cytogenetic abnormalities in natural killer cell lymphoma/leukaemia--is there a consistent pattern?". Leukemia & Lymphoma. 34 (3–4): 241–250. doi:10.3109/10428199909050949. ISSN 1042-8194. PMID 10439361. Check date values in: |date= (help)
  22. ↑ Ko, Y. H.; et al. (2001-04-15). "Comparative genomic hybridization study of nasal-type NK/T-cell lymphoma". Cytometry. 46 (2): 85–91. doi:10.1002/cyto.1069. ISSN 0196-4763. PMID 11309817.
  23. ↑ Iqbal, J.; et al. (2009-06). "Genomic analyses reveal global functional alterations that promote tumor growth and novel tumor suppressor genes in natural killer-cell malignancies". Leukemia. 23 (6): 1139–1151. doi:10.1038/leu.2009.3. ISSN 1476-5551. PMID 19194464. Check date values in: |date= (help)
  24. ↑ Karube, Kennosuke; et al. (2011-09-22). "Identification of FOXO3 and PRDM1 as tumor-suppressor gene candidates in NK-cell neoplasms by genomic and functional analyses". Blood. 118 (12): 3195–3204. doi:10.1182/blood-2011-04-346890. ISSN 1528-0020. PMID 21690554.
  25. ↑ 25.0 25.1 25.2 25.3 Chen, Yun-Wen; et al. (2015-03-05). "Receptor-type tyrosine-protein phosphatase κ directly targets STAT3 activation for tumor suppression in nasal NK/T-cell lymphoma". Blood. 125 (10): 1589–1600. doi:10.1182/blood-2014-07-588970. ISSN 1528-0020. PMID 25612622.
  26. ↑ Koo, Ghee Chong; et al. (2012-07). "Janus kinase 3-activating mutations identified in natural killer/T-cell lymphoma". Cancer Discovery. 2 (7): 591–597. doi:10.1158/2159-8290.CD-12-0028. ISSN 2159-8290. PMID 22705984. Check date values in: |date= (help)
  27. ↑ Bouchekioua, A.; et al. (2014-02). "JAK3 deregulation by activating mutations confers invasive growth advantage in extranodal nasal-type natural killer cell lymphoma". Leukemia. 28 (2): 338–348. doi:10.1038/leu.2013.157. ISSN 1476-5551. PMID 23689514. Check date values in: |date= (help)
  28. ↑ Nairismägi, M.-L.; et al. (2018-05). "Oncogenic activation of JAK3-STAT signaling confers clinical sensitivity to PRN371, a novel selective and potent JAK3 inhibitor, in natural killer/T-cell lymphoma". Leukemia. 32 (5): 1147–1156. doi:10.1038/s41375-017-0004-x. ISSN 1476-5551. PMC 5940653. PMID 29434279. Check date values in: |date= (help)
  29. ↑ 29.0 29.1 29.2 29.3 Jiang, Lu; et al. (2015-09). "Exome sequencing identifies somatic mutations of DDX3X in natural killer/T-cell lymphoma". Nature Genetics. 47 (9): 1061–1066. doi:10.1038/ng.3358. ISSN 1546-1718. PMID 26192917. Check date values in: |date= (help)
  30. ↑ 30.0 30.1 Küçük, Can; et al. (2015-01-14). "Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells". Nature Communications. 6: 6025. doi:10.1038/ncomms7025. ISSN 2041-1723. PMC 7743911 Check |pmc= value (help). PMID 25586472.
  31. ↑ 31.0 31.1 Lee, Seungbok; et al. (2015-07-10). "Genetic alterations of JAK/STAT cascade and histone modification in extranodal NK/T-cell lymphoma nasal type". Oncotarget. 6 (19): 17764–17776. doi:10.18632/oncotarget.3776. ISSN 1949-2553. PMC 4627344. PMID 25980440.
  32. ↑ Wang, Yali; et al. (2023-08). "Preclinical characterization of WB737, a potent and selective STAT3 inhibitor, in natural killer/T-cell lymphoma". MedComm. 4 (4): e284. doi:10.1002/mco2.284. ISSN 2688-2663. PMC PMC10274570 Check |pmc= value (help). PMID 37334274 Check |pmid= value (help). Check date values in: |date= (help)CS1 maint: PMC format (link)
  33. ↑ Quintanilla-Martinez, L.; et al. (2001-12). "p53 Mutations in nasal natural killer/T-cell lymphoma from Mexico: association with large cell morphology and advanced disease". The American Journal of Pathology. 159 (6): 2095–2105. doi:10.1016/S0002-9440(10)63061-1. ISSN 0002-9440. PMC 1850589. PMID 11733360. Check date values in: |date= (help)
  34. ↑ Hongyo, Tadashi; et al. (2005-02). "p53, K-ras, c-kit and beta-catenin gene mutations in sinonasal NK/T-cell lymphoma in Korea and Japan". Oncology Reports. 13 (2): 265–271. ISSN 1021-335X. PMID 15643509. Check date values in: |date= (help)

Notes

*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. *Citation of this Page: “Extranodal NK/T-cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 06/21/2024, https://ccga.io/index.php/HAEM5:Extranodal_NK/T-cell_lymphoma.

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