HAEM5:Aggressive NK-cell leukaemia - Revision history

Bailey.Glen at 17:09, 3 July 2025

2025-07-03T17:09:08Z

← Older revision		Revision as of 12:09, 3 July 2025
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	Aggressive NK-cell Leukaemia		Aggressive NK-cell Leukaemia

	~~==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==		==Related Terminology==

Bailey.Glen at 21:28, 25 May 2025

2025-05-25T21:28:31Z

← Older revision		Revision as of 16:28, 25 May 2025
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	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-
	!Chr #!!~~'''~~Gain, Loss, Amp, LOH~~'''~~!!~~'''~~Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]~~'''~~!!~~'''~~Relevant Gene(s)~~'''~~		!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
	!~~'''~~Diagnostic, Prognostic, and Therapeutic Significance - D, P, T~~'''~~		!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
	!~~'''~~Established Clinical Significance Per Guidelines - Yes or No (Source)~~'''~~		!Established Clinical Significance Per Guidelines - Yes or No (Source)
	!~~'''~~Clinical Relevance Details/Other Notes~~'''~~		!Clinical Relevance Details/Other Notes
	\|-		\|-
	\|<span class="blue-text">EXAMPLE:</span>		\|<span class="blue-text">EXAMPLE:</span>
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	!Chromosomal Pattern		!Chromosomal Pattern
	!Molecular Pathogenesis		!Molecular Pathogenesis
	!~~'''~~Prevalence -~~'''~~		!Prevalence -
	~~'''~~Common >20%, Recurrent 5-20% or Rare <5% (Disease)~~'''~~		Common >20%, Recurrent 5-20% or Rare <5% (Disease)
	!~~'''~~Diagnostic, Prognostic, and Therapeutic Significance - D, P, T~~'''~~		!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
	!~~'''~~Established Clinical Significance Per Guidelines - Yes or No (Source)~~'''~~		!Established Clinical Significance Per Guidelines - Yes or No (Source)
	!~~'''~~Clinical Relevance Details/Other Notes~~'''~~		!Clinical Relevance Details/Other Notes
	\|-		\|-
	\|<span class="blue-text">EXAMPLE:</span>		\|<span class="blue-text">EXAMPLE:</span>
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	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-
	!Gene!!~~'''~~Genetic Alteration~~'''~~!!~~'''~~Tumor Suppressor Gene, Oncogene, Other~~'''~~!!~~'''~~Prevalence -~~'''~~		!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
	~~'''~~Common >20%, Recurrent 5-20% or Rare <5% (Disease)~~'''~~		Common >20%, Recurrent 5-20% or Rare <5% (Disease)
	!~~'''~~Diagnostic, Prognostic, and Therapeutic Significance - D, P, T ~~'''~~		!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
	!~~'''~~Established Clinical Significance Per Guidelines - Yes or No (Source)~~'''~~		!Established Clinical Significance Per Guidelines - Yes or No (Source)
	!~~'''~~Clinical Relevance Details/Other Notes~~'''~~		!Clinical Relevance Details/Other Notes
	\|-		\|-
	\|<span class="blue-text">EXAMPLE:</span>''EGFR''		\|<span class="blue-text">EXAMPLE:</span>''EGFR''
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	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-
	!Gene; Genetic Alteration!!~~'''~~Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)~~'''~~!!~~'''~~Prevalence (COSMIC / TCGA / Other)~~'''~~!!~~'''~~Concomitant Mutations~~'''~~!!~~'''~~Mutually Exclusive Mutations~~'''~~		!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)~~'''~~		!Diagnostic Significance (Yes, No or Unknown)
	!Prognostic Significance (Yes, No or Unknown)		!Prognostic Significance (Yes, No or Unknown)
	!Therapeutic Significance (Yes, No or Unknown)		!Therapeutic Significance (Yes, No or Unknown)

Bailey.Glen at 20:04, 25 May 2025

2025-05-25T20:04:56Z

← Older revision		Revision as of 15:04, 25 May 2025
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	<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>].		<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==		==Related Terminology==
	~~<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>~~
	{\| class="wikitable"		{\| class="wikitable"
	\|+		\|+
	\|Acceptable		\|Acceptable
	\|		\|Aggressive NK-cell leukaemia/lymphoma
	\|-		\|-
	\|Not Recommended		\|Not Recommended
	\|		\|NK-large granular lymphocyte leukaemia; aggressive large granular lymphocyte leukaemia
	\|}		\|}

Bailey.Glen at 17:31, 24 March 2025

2025-03-24T17:31:42Z

← Older revision		Revision as of 12:31, 24 March 2025
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	{{DISPLAYTITLE:Aggressive NK-cell leukaemia}}		{{DISPLAYTITLE:Aggressive NK-cell leukaemia}}

	[[HAEM5:Table_of_Contents\|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]		[[HAEM5:Table_of_Contents\|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]

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	Case Western Reserve University, Cleveland, OH		Case Western Reserve University, Cleveland, OH

	~~__TOC__~~

	==WHO Classification of Disease==		==WHO Classification of Disease==

Jennelleh at 10:54, 19 February 2025

2025-02-19T10:54:48Z

← Older revision		Revision as of 05:54, 19 February 2025
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	[[HAEM5:Extranodal NK/T-cell lymphoma\|Extranodal NK/T-cell lymphoma]]		[[HAEM5:Extranodal NK/T-cell lymphoma\|Extranodal NK/T-cell lymphoma]]

	[[HAEM5:Hepatosplenic T-cell lymphoma\|Hepatosplenic T-cell Lymphoma ~~(HSTCL)~~]]		[[HAEM5:Hepatosplenic T-cell lymphoma\|Hepatosplenic T-cell Lymphoma]]

	[[HAEM5:NK-large granular lymphocytic leukaemia\|~~Chronic lymphoproliferative disorder of natural killer cells (CLPD~~-~~NK)~~]]		[[HAEM5:NK-large granular lymphocytic leukaemia\|NK-large Granular Lymphocytic Leukaemia]]

	==References==		==References==

Jennelleh at 10:53, 19 February 2025

2025-02-19T10:53:33Z

Jennelleh at 10:47, 19 February 2025

2025-02-19T10:47:43Z

Show changes

Jennelleh at 10:38, 19 February 2025

2025-02-19T10:38:08Z

@@ Line 30: / Line 30: @@
 ==Epidemiology / Prevalence==
-Aggressive NK-cell leukaemia impacts young to middle-aged adults with peak incidence during 3rd and 5th decades of life (Mean age: 40 years).<ref name=":1" /> There is no gender predilection and most prevalent in Asia, Central and South America.<ref name=":0">{{Cite journal|last=El Hussein|first=Siba|last2=Patel|first2=Keyur P.|last3=Fang|first3=Hong|last4=Thakral|first4=Beenu|last5=Loghavi|first5=Sanam|last6=Kanagal-Shamanna|first6=Rashmi|last7=Konoplev|first7=Sergej|last8=Jabbour|first8=Elias J.|last9=Medeiros|first9=L. Jeffrey|date=09 2020|title=Genomic and Immunophenotypic Landscape of Aggressive NK-Cell Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/32590457|journal=The American Journal of Surgical Pathology|volume=44|issue=9|pages=1235–1243|doi=10.1097/PAS.0000000000001518|issn=1532-0979|pmid=32590457}}</ref> Median survival is very short, <2 months. EBV-negative cases tend to occur in older patients, with no significant difference in Asian vs. non-Asian populations.<ref name=":2">{{Cite journal|last=El Hussein|first=Siba|last2=Medeiros|first2=L. Jeffrey|last3=Khoury|first3=Joseph D.|date=10 09, 2020|title=Aggressive NK Cell Leukemia: Current State of the Art|url=https://pubmed.ncbi.nlm.nih.gov/33050313|journal=Cancers|volume=12|issue=10|doi=10.3390/cancers12102900|issn=2072-6694|pmc=7600035|pmid=33050313}}</ref> EBV-negative cases may occur de novo or transform from chronic lymphoproliferative disorder of NK cells.'''''<ref name=":4" />'''''
+Aggressive NK-cell leukaemia impacts young to middle-aged adults with peak incidence during 3rd and 5th decades of life (Mean age: 40 years).<ref name=":1">Chan, JKC et al., (2017). Aggressive NK-cell leukaemia, 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, p353-354.</ref> There is no gender predilection and most prevalent in Asia, Central and South America.<ref name=":0">{{Cite journal|last=El Hussein|first=Siba|last2=Patel|first2=Keyur P.|last3=Fang|first3=Hong|last4=Thakral|first4=Beenu|last5=Loghavi|first5=Sanam|last6=Kanagal-Shamanna|first6=Rashmi|last7=Konoplev|first7=Sergej|last8=Jabbour|first8=Elias J.|last9=Medeiros|first9=L. Jeffrey|date=09 2020|title=Genomic and Immunophenotypic Landscape of Aggressive NK-Cell Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/32590457|journal=The American Journal of Surgical Pathology|volume=44|issue=9|pages=1235–1243|doi=10.1097/PAS.0000000000001518|issn=1532-0979|pmid=32590457}}</ref> Median survival is very short, <2 months. EBV-negative cases tend to occur in older patients, with no significant difference in Asian vs. non-Asian populations.<ref name=":2">{{Cite journal|last=El Hussein|first=Siba|last2=Medeiros|first2=L. Jeffrey|last3=Khoury|first3=Joseph D.|date=10 09, 2020|title=Aggressive NK Cell Leukemia: Current State of the Art|url=https://pubmed.ncbi.nlm.nih.gov/33050313|journal=Cancers|volume=12|issue=10|doi=10.3390/cancers12102900|issn=2072-6694|pmc=7600035|pmid=33050313}}</ref> EBV-negative cases may occur de novo or transform from chronic lymphoproliferative disorder of NK cells.'''''<ref name=":4">{{Cite journal|last=Kim|first=Wook Youn|last2=Montes-Mojarro|first2=Ivonne A.|last3=Fend|first3=Falko|last4=Quintanilla-Martinez|first4=Leticia|date=2019|title=Epstein-Barr Virus-Associated T and NK-Cell Lymphoproliferative Diseases|url=https://pubmed.ncbi.nlm.nih.gov/30931288|journal=Frontiers in Pediatrics|volume=7|pages=71|doi=10.3389/fped.2019.00071|issn=2296-2360|pmc=6428722|pmid=30931288}}</ref>'''''
 ==Clinical Features==
@@ Line 59: / Line 53: @@
-<blockquote class="blockedit">{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}</blockquote>
+<nowiki>*</nowiki>EBV-negative cases may occur ''de novo'' or transform from chronic lymphoproliferative disorder of NK cells
 ==Sites of Involvement==
-Peripheral blood, bone marrow, liver, spleen, and lymph nodes are frequently involved. Extranodal involvement sites are organs including skin, lungs, soft tissue and omentum has also been reported.<ref name=":5" />
+Peripheral blood, bone marrow, liver, spleen, and lymph nodes are frequently involved. Extranodal involvement sites are organs including skin, lungs, soft tissue and omentum has also been reported.<ref name=":5">{{Cite journal|last=Hue|first=Susan Swee-Shan|last2=Oon|first2=Ming Liang|last3=Wang|first3=Shi|last4=Tan|first4=Soo-Yong|last5=Ng|first5=Siok-Bian|date=2020-01|title=Epstein–Barr virus-associated T- and NK-cell lymphoproliferative diseases: an update and diagnostic approach|url=https://linkinghub.elsevier.com/retrieve/pii/S0031302519304210|journal=Pathology|language=en|volume=52|issue=1|pages=111–127|doi=10.1016/j.pathol.2019.09.011}}</ref>
 ==Morphologic Features==
@@ Line 119: / Line 80: @@
 *+/- angioinvasion
 ==Immunophenotype==
@@ Line 139: / Line 95: @@
 |Negative (subset)||CD7, CD45
 |}
 ==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>
@@ Line 485: / Line 435: @@
 <nowiki>*</nowiki>Thought in some cases to be as a result of highly expressed EBV-encoded small RNAs (EBERs) causing release of IL-10.<ref name=":2" />
 ==Genetic Diagnostic Testing Methods==
 Foundation of diagnosis based on morphology with immunophenotyping via flow cytometry +/- immunohistochemistry.<ref name=":0" />
 ==Familial Forms==

Bailey.Glen: /* Gene Mutations (SNV/INDEL) */

2025-02-14T00:36:55Z

Gene Mutations (SNV/INDEL)

@@ Line 340: / Line 340: @@
 ==Gene Mutations (SNV/INDEL)==
 Mutations in the ''JAK-STAT'' pathway appear to be mutually exclusive.<ref name=":3">{{Cite journal|last=Huang|first=Liang|last2=Liu|first2=Dan|last3=Wang|first3=Na|last4=Ling|first4=Shaoping|last5=Tang|first5=Yuting|last6=Wu|first6=Jun|last7=Hao|first7=Lingtong|last8=Luo|first8=Hui|last9=Hu|first9=Xuelian|date=2018-02|title=Integrated genomic analysis identifies deregulated JAK/STAT-MYC-biosynthesis axis in aggressive NK-cell leukemia|url=http://www.nature.com/articles/cr2017146|journal=Cell Research|language=en|volume=28|issue=2|pages=172–186|doi=10.1038/cr.2017.146|issn=1001-0602|pmc=PMC5799812|pmid=29148541}}</ref> Most ''STAT3'' and ''STAT5B''  mutations localized to exons 20 and 21 encoding the Src homology 2 (SH2) domain, which causes ''STAT'' dimerization. Other mutations identified: 9p copy gains (containing ''JAK2),'' point mutation in protein tyrosine phosphatase (''PTPRK'') (tumor suppressor that negatively regulates ''STAT3''). mutations in ''PTPN4'' and ''PTPN23.<ref name=":2" /><ref name=":7">{{Cite journal|last=Gao|first=Juehua|last2=Zhang|first2=Yanming|last3=Yaseen|first3=Nabeel R.|last4=Fang|first4=Yuqiang|last5=Lu|first5=Xinyan|last6=Sukhanova|first6=Madina|last7=Chen|first7=Qing|last8=Chen|first8=Yi-Hua|date=2020-11|title=Comprehensive molecular genetic studies of Epstein-Barr virus-negative aggressive Natural killer-cell leukemia/lymphoma|url=https://linkinghub.elsevier.com/retrieve/pii/S0046817720301702|journal=Human Pathology|language=en|volume=105|pages=20–30|doi=10.1016/j.humpath.2020.08.008}}</ref>''
@@ Line 396: / Line 440: @@
 <br />
 ==Epigenomic Alterations==

Bailey.Glen: /* Characteristic Chromosomal or Other Global Mutational Patterns */

2025-02-14T00:36:13Z

Characteristic Chromosomal or Other Global Mutational Patterns

@@ Line 304: / Line 304: @@
 Due to rare nature of disease, cytogenetics data is limited. The common abnormalities include del(6)(q21q25) and del(11q), however, none of these abnormalities are specific and their clinical significance is unknown.<ref name=":2" /> Complex karyotypes with unbalanced rearrangements are frequently seen.
 ==Gene Mutations (SNV/INDEL)==
 Mutations in the ''JAK-STAT'' pathway appear to be mutually exclusive.<ref name=":3">{{Cite journal|last=Huang|first=Liang|last2=Liu|first2=Dan|last3=Wang|first3=Na|last4=Ling|first4=Shaoping|last5=Tang|first5=Yuting|last6=Wu|first6=Jun|last7=Hao|first7=Lingtong|last8=Luo|first8=Hui|last9=Hu|first9=Xuelian|date=2018-02|title=Integrated genomic analysis identifies deregulated JAK/STAT-MYC-biosynthesis axis in aggressive NK-cell leukemia|url=http://www.nature.com/articles/cr2017146|journal=Cell Research|language=en|volume=28|issue=2|pages=172–186|doi=10.1038/cr.2017.146|issn=1001-0602|pmc=PMC5799812|pmid=29148541}}</ref> Most ''STAT3'' and ''STAT5B''  mutations localized to exons 20 and 21 encoding the Src homology 2 (SH2) domain, which causes ''STAT'' dimerization. Other mutations identified: 9p copy gains (containing ''JAK2),'' point mutation in protein tyrosine phosphatase (''PTPRK'') (tumor suppressor that negatively regulates ''STAT3''). mutations in ''PTPN4'' and ''PTPN23.<ref name=":2" /><ref name=":7">{{Cite journal|last=Gao|first=Juehua|last2=Zhang|first2=Yanming|last3=Yaseen|first3=Nabeel R.|last4=Fang|first4=Yuqiang|last5=Lu|first5=Xinyan|last6=Sukhanova|first6=Madina|last7=Chen|first7=Qing|last8=Chen|first8=Yi-Hua|date=2020-11|title=Comprehensive molecular genetic studies of Epstein-Barr virus-negative aggressive Natural killer-cell leukemia/lymphoma|url=https://linkinghub.elsevier.com/retrieve/pii/S0046817720301702|journal=Human Pathology|language=en|volume=105|pages=20–30|doi=10.1016/j.humpath.2020.08.008}}</ref>''

← Older revision		Revision as of 05:53, 19 February 2025
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	This disease is <u>defined/characterized</u> as detailed below:		This disease is <u>defined/characterized</u> as detailed below:

	* Aggressive NK-cell leukaemia is a malignant proliferation of NK-cells, often associated with EBV infection, however, a subset of cases could be EBV negative. The disease has an extremely aggressive clinical course with poor response to chemotherapy, frequent relapses noted in patient who have had previously achieved complete remission (+/- bone marrow transplantation).		*Aggressive NK-cell leukaemia is a malignant proliferation of NK-cells, often associated with EBV infection, however, a subset of cases could be EBV negative. The disease has an extremely aggressive clinical course with poor response to chemotherapy, frequent relapses noted in patient who have had previously achieved complete remission (+/- bone marrow transplantation).

	The <u>epidemiology/prevalence</u> of this disease is detailed below:		The <u>epidemiology/prevalence</u> of this disease is detailed below:

	* Aggressive NK-cell leukaemia impacts young to middle-aged adults with peak incidence during 3rd and 5th decades of life (Mean age: 40 years).<ref name=":1" /> There is no gender predilection and most prevalent in Asia, Central and South America.<ref name=":0" /> Median survival is very short, <2 months. EBV-negative cases tend to occur in older patients, with no significant difference in Asian vs. non-Asian populations.<ref name=":2" /> EBV-negative cases may occur de novo or transform from chronic lymphoproliferative disorder of NK cells.'''''<ref name=":4">{{Cite journal\|last=Kim\|first=Wook Youn\|last2=Montes-Mojarro\|first2=Ivonne A.\|last3=Fend\|first3=Falko\|last4=Quintanilla-Martinez\|first4=Leticia\|date=2019\|title=Epstein-Barr Virus-Associated T and NK-Cell Lymphoproliferative Diseases\|url=https://pubmed.ncbi.nlm.nih.gov/30931288\|journal=Frontiers in Pediatrics\|volume=7\|pages=71\|doi=10.3389/fped.2019.00071\|issn=2296-2360\|pmc=6428722\|pmid=30931288}}</ref>'''''		*Aggressive NK-cell leukaemia impacts young to middle-aged adults with peak incidence during 3rd and 5th decades of life (Mean age: 40 years).<ref name=":1" /> There is no gender predilection and most prevalent in Asia, Central and South America.<ref name=":0" /> Median survival is very short, <2 months. EBV-negative cases tend to occur in older patients, with no significant difference in Asian vs. non-Asian populations.<ref name=":2" /> EBV-negative cases may occur de novo or transform from chronic lymphoproliferative disorder of NK cells.'''''<ref name=":4">{{Cite journal\|last=Kim\|first=Wook Youn\|last2=Montes-Mojarro\|first2=Ivonne A.\|last3=Fend\|first3=Falko\|last4=Quintanilla-Martinez\|first4=Leticia\|date=2019\|title=Epstein-Barr Virus-Associated T and NK-Cell Lymphoproliferative Diseases\|url=https://pubmed.ncbi.nlm.nih.gov/30931288\|journal=Frontiers in Pediatrics\|volume=7\|pages=71\|doi=10.3389/fped.2019.00071\|issn=2296-2360\|pmc=6428722\|pmid=30931288}}</ref>'''''

	The <u>clinical features</u> of this disease are detailed below:		The <u>clinical features</u> of this disease are detailed below:

	* Most common presentation is with constitutional symptoms and frequently associated hepatosplenomegaly is noted on physical examination.<ref name=":1" /><ref name=":4" /> EBV-negative cases may occur ''de novo'' or transform from chronic lymphoproliferative disorder of NK cells.		*Most common presentation is with constitutional symptoms and frequently associated hepatosplenomegaly is noted on physical examination.<ref name=":1" /><ref name=":4" /> EBV-negative cases may occur ''de novo'' or transform from chronic lymphoproliferative disorder of NK cells.

	Signs and symptoms - Constitutional symptoms (weight loss, fever, night sweats); Hepatosplenomegaly common; Frequently complicated by multiorgan failure, coagulopathy and haemophagocytic syndrome		Signs and symptoms - Constitutional symptoms (weight loss, fever, night sweats); Hepatosplenomegaly common; Frequently complicated by multiorgan failure, coagulopathy and haemophagocytic syndrome
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	The <u>sites of involvement</u> of this disease are detailed below:		The <u>sites of involvement</u> of this disease are detailed below:

	* Peripheral blood, bone marrow, liver, spleen, and lymph nodes are frequently involved. Extranodal involvement sites are organs including skin, lungs, soft tissue and omentum has also been reported.<ref name=":5">{{Cite journal\|last=Hue\|first=Susan Swee-Shan\|last2=Oon\|first2=Ming Liang\|last3=Wang\|first3=Shi\|last4=Tan\|first4=Soo-Yong\|last5=Ng\|first5=Siok-Bian\|date=2020-01\|title=Epstein–Barr virus-associated T- and NK-cell lymphoproliferative diseases: an update and diagnostic approach\|url=https://linkinghub.elsevier.com/retrieve/pii/S0031302519304210\|journal=Pathology\|language=en\|volume=52\|issue=1\|pages=111–127\|doi=10.1016/j.pathol.2019.09.011}}</ref>		*Peripheral blood, bone marrow, liver, spleen, and lymph nodes are frequently involved. Extranodal involvement sites are organs including skin, lungs, soft tissue and omentum has also been reported.<ref name=":5">{{Cite journal\|last=Hue\|first=Susan Swee-Shan\|last2=Oon\|first2=Ming Liang\|last3=Wang\|first3=Shi\|last4=Tan\|first4=Soo-Yong\|last5=Ng\|first5=Siok-Bian\|date=2020-01\|title=Epstein–Barr virus-associated T- and NK-cell lymphoproliferative diseases: an update and diagnostic approach\|url=https://linkinghub.elsevier.com/retrieve/pii/S0031302519304210\|journal=Pathology\|language=en\|volume=52\|issue=1\|pages=111–127\|doi=10.1016/j.pathol.2019.09.011}}</ref>

	The <u>morphologic features</u> of this disease are detailed below:		The <u>morphologic features</u> of this disease are detailed below:
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	The <u>immunophenotype</u> of this disease is detailed below:		The <u>immunophenotype</u> of this disease is detailed below:

	* The leukaemic cells show demonstrate the following phenotypic expression.<ref name=":1" /><ref name=":0" />		*The leukaemic cells show demonstrate the following phenotypic expression.<ref name=":1" /><ref name=":0" />

	Positive (universal) - CD2, CD3-epsilon, CD56, CD94, cytotoxic molecules (TIA1, Granzyme B, perforin A), FASL, c-MYC		Positive (universal) - CD2, CD3-epsilon, CD56, CD94, cytotoxic molecules (TIA1, Granzyme B, perforin A), FASL, c-MYC
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	[[HAEM5:Extranodal NK/T-cell lymphoma\|Extranodal NK/T-cell lymphoma]]		[[HAEM5:Extranodal NK/T-cell lymphoma\|Extranodal NK/T-cell lymphoma]]

	[[Hepatosplenic T-cell Lymphoma (HSTCL)]]		[[HAEM5:Hepatosplenic T-cell lymphoma\|Hepatosplenic T-cell Lymphoma (HSTCL)]]

	[[Chronic lymphoproliferative disorder of natural killer cells (CLPD-NK)]]		[[HAEM5:NK-large granular lymphocytic leukaemia\|Chronic lymphoproliferative disorder of natural killer cells (CLPD-NK)]]

	==References==		==References==