Compendium of Cancer Genome Aberrations

HAEM5:NK-large granular lymphocytic leukaemia: Difference between revisions

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{{DISPLAYTITLE:NK-large granular lymphocytic leukaemia}}
{{DISPLAYTITLE:NK-large granular lymphocytic leukaemia}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]


{{Under Construction}}
{{Under Construction}}


<blockquote class='blockedit'>{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Chronic Lymphoproliferative Disorder of NK Cells]].
<blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Chronic Lymphoproliferative Disorder of NK Cells]].
}}</blockquote>
}}</blockquote>


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Michelle Don, MD, UC San Diego
Michelle Don, MD, UC San Diego
__TOC__
==WHO Classification of Disease==
==WHO Classification of Disease==


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|NK-large granular lymphocytic leukaemia
|NK-large granular lymphocytic leukaemia
|}
|}
==Related Terminology==


==Definition / Description of Disease==
A neoplasm characterized by a persistent (>6 months) increase in peripheral NK cells (> 2 x 10^9/L) and a chronic indolent clinical course. Additional essential diagnostic criteria include flow cytometric evidence of peripheral blood or bone marrow involvement by a uniform population of sCD3(-), CD16(+) NK cells and demonstration of a restricted pattern of KIR expression.
The differential diagnosis includes other mature T-cell neoplasms with a leukemic presentation. T-cell large granular lymphocytic leukemia is a disorder with clinical and pathological overlap; NK-LGL cannot be distinguished from T-LGL by cytological features. If there is prominent lymphocytosis, an aggressive NK-cell leukemia can be considered and NK-LGL is distinguished by an indolent clinical presentation and lack of nuclear EBV positivity. <ref name=":0" />
==Synonyms / Terminology==
*Chronic lymphoproliferative disorder of NK cells
*Chronic NK-large granular lymphocyte lymphoproliferative disorder
*Chronic NK-cell lymphocytosis (historical)
*Indolent leukemia of NK cells (historical) <ref name=":0" />
==Epidemiology / Prevalence==
*Median age: 60 years
*Does not show sex, racial, geographical, or genetic predisposition <ref name=":0" />
==Clinical Features==
{| class="wikitable"
{| class="wikitable"
|'''Signs and Symptoms'''
|+
|Asymptomatic (incidental finding on complete blood counts)
|Acceptable
May occur in association with autoimmune disorders, solid tumors, hematological neoplasms, and neuropathy
|Chronic lymphoproliferative disorder of NK cells; chronic NK-large granular lymphocyte lymphoproliferative disorder
 
Uncommon/atypical: splenomegaly, hepatomegaly, lymphadenopathy, skin involvement <ref name=":0" />
|-
|-
|'''Laboratory Findings'''
|Not Recommended
|Lymphocytosis, variable neutropenia and/or anemia <ref name=":0" />
|Chronic NK-cell lymphocytosis; indolent leukaemia of NK cells
|}
|}


==Sites of Involvement==
==Gene Rearrangements==
 
None
*Peripheral blood and bone marrow
 
*Uncommon: spleen <ref name=":0" />
 
==Morphologic Features==
 
*NK-cells are typically intermediate to large in size with small, round nuclei and moderate cytoplasm with fine or coarse azurophilic granules.
 
*Intrasinusoidal and sometimes interstitial infiltration of bone marrow and possibly spleen. <ref name=":0" />
 
==Immunophenotype <ref name=":0" />==
 
{| 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||CD16
|
|
|
|
|
|
|
|
|}
 
==Individual Region Genomic Gain/Loss/LOH==
None
{| class="wikitable sortable"
|-
|-
|Positive||cytoplasmic CD3-epsilon
!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
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|Positive (frequent)||CD56
|
|
|
|
|
|
|
|}
 
==Characteristic Chromosomal or Other Global Mutational Patterns==
None
{| class="wikitable sortable"
|-
|-
|Positive||Cytotoxic markers
!Chromosomal Pattern
(TIA1, granzyme B & granzyme M)
!Molecular Pathogenesis
!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
|CD94
|-
|Decreased to negative
|CD2, CD7, CD57, CD161
|-
|Negative
|surface CD3
|-
|Restricted or lack of expression
|KIR isoforms (CD158a, b, c)
|-
|Negative
|EBV
|}
==WHO Essential and Desirable Genetic Diagnostic Criteria==
<span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span>
{| class="wikitable"
|+
|WHO Essential Criteria (Genetics)*
|
|
|-
|WHO Desirable Criteria (Genetics)*
|
|
|-
|Other Classification
|
|
|}
<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
==Related Terminology==
<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>
{| class="wikitable"
|+
|Acceptable
|
|
|-
|
|Not Recommended
|
|
|}
|}


==Gene Rearrangements==
None
==Individual Region Genomic Gain/Loss/LOH==
None
==Characteristic Chromosomal or Other Global Mutational Patterns==
None
==Gene Mutations (SNV/INDEL)==
==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 or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries 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. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
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 or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries 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. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
{| 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)
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==Additional Information==
==Additional Information==


None
This disease is <u>defined/characterized</u> as detailed below:
 
*A neoplasm characterized by a persistent (>6 months) increase in peripheral NK cells (> 2 x 10^9/L) and a chronic indolent clinical course. Additional essential diagnostic criteria include flow cytometric evidence of peripheral blood or bone marrow involvement by a uniform population of sCD3(-), CD16(+) NK cells and demonstration of a restricted pattern of KIR expression.
*The differential diagnosis includes other mature T-cell neoplasms with a leukemic presentation. T-cell large granular lymphocytic leukemia is a disorder with clinical and pathological overlap; NK-LGL cannot be distinguished from T-LGL by cytological features. If there is prominent lymphocytosis, an aggressive NK-cell leukemia can be considered and NK-LGL is distinguished by an indolent clinical presentation and lack of nuclear EBV positivity.<ref name=":0">WHO Classification of Tumours Editorial Board, eds, WHO Classification of Tumours, Haematolymphoid Tumours Part A. 5th edition, IARC Press:Lyon, 2024.</ref>
 
The <u>epidemiology/prevalence</u> of this disease is detailed below:
 
*Median age: 60 years
 
*Does not show sex, racial, geographical, or genetic predisposition<ref name=":0" />
 
The <u>clinical features</u> of this disease are detailed below:
 
*Signs and symptoms - Asymptomatic (incidental finding on complete blood counts); May occur in association with autoimmune disorders, solid tumors, hematological neoplasms, and neuropathy; Uncommon/atypical: splenomegaly, hepatomegaly, lymphadenopathy, skin involvement<ref name=":0" />
*Laboratory findings - Lymphocytosis, variable neutropenia and/or anemia<ref name=":0" />
 
The <u>sites of involvement</u> of this disease are detailed below:
 
*Peripheral blood and bone marrow
 
*Uncommon: spleen<ref name=":0" />
 
The <u>morphologic features</u> of this disease are detailed below:
 
*NK-cells are typically intermediate to large in size with small, round nuclei and moderate cytoplasm with fine or coarse azurophilic granules.
 
*Intrasinusoidal and sometimes interstitial infiltration of bone marrow and possibly spleen.<ref name=":0" />
 
The <u>immunophenotype</u> of this disease is detailed below:
 
Positive - CD16, cytoplasmic CD3-epsilon, Cytotoxic markers (TIA1, granzyme B & granzyme M), CD94
 
Positive (frequent) - CD56
 
Decreased to negative - CD2, CD7, CD57, CD161
 
Restricted or lack of expression - KIR isoforms (CD158a, b, c)
 
Negative - surface CD3, EBV


==Links==
==Links==


<br />
N/A<br />


==References==
==References==
Retrieved from "https://test.ccga.io/index.php/HAEM5:NK-large_granular_lymphocytic_leukaemia"