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.)]]


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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"
|'''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" />
|}
==Sites of Involvement==
*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"
|-
!Finding!!Marker
|-
|Positive||CD16
|-
|Positive||cytoplasmic CD3-epsilon
|-
|Positive (frequent)||CD56
|-
|Positive||Cytotoxic markers
(TIA1, granzyme B & granzyme M)
|-
|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"
{| class="wikitable"
|+
|+
|Acceptable
|Acceptable
|
|Chronic lymphoproliferative disorder of NK cells; chronic NK-large granular lymphocyte lymphoproliferative disorder
|-
|-
|Not Recommended
|Not Recommended
|
|Chronic NK-cell lymphocytosis; indolent leukaemia of NK cells
|}
|}


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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
|-
|-
|
|
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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
|-
|-
|
|
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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)
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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==
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