Compendium of Cancer Genome Aberrations

HAEM5:Hepatosplenic T-cell lymphoma: Difference between revisions

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{{DISPLAYTITLE:Hepatosplenic T-cell lymphoma}}
==Primary Author(s)*==
==Primary Author(s)*==
Forough Sargolzaeiaval, MD


*Forough Sargolzaeiaval, MD
Michelle Don, MD, MS
*Michelle Don, MD, MS


==WHO Classification of Disease==
==WHO Classification of Disease==
Line 27: Line 25:
|Hepatosplenic T-cell lymphoma
|Hepatosplenic T-cell lymphoma
|}
|}
==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==


{| class="wikitable"
{| class="wikitable"
|+
|Acceptable
|Acceptable
|N/A
|N/A
Line 53: Line 36:


==Gene Rearrangements==
==Gene Rearrangements==
 
No known chromosomal rearrangements at this time.
*No known chromosomal rearrangements at this time
 
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
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|-
|-
|N/A
|N/A
|
|N/A
|
|N/A
|
|N/A
|
|N/A
|
|N/A
|
|N/A
|
|N/A
|}
|}


Line 82: Line 63:
!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|7
7
|<span class="blue-text">EXAMPLE:</span> Loss
|<span class="blue-text">EXAMPLE:</span>
chr7
|<span class="blue-text">EXAMPLE:</span>
Unknown
|<span class="blue-text">EXAMPLE:</span> D, P
|<span class="blue-text">EXAMPLE:</span> No
|<span class="blue-text">EXAMPLE:</span>
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 references).
|-
|<span class="blue-text">EXAMPLE:</span>
8
|<span class="blue-text">EXAMPLE:</span> Gain
|<span class="blue-text">EXAMPLE:</span>
chr8
|<span class="blue-text">EXAMPLE:</span>
Unknown
|<span class="blue-text">EXAMPLE:</span> D, P
|
|<span class="blue-text">EXAMPLE:</span>
Common recurrent secondary finding for t(8;21) (add references).
|-
|<span class="blue-text">EXAMPLE:</span>
17
|<span class="blue-text">EXAMPLE:</span> Amp
|<span class="blue-text">EXAMPLE:</span>
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
|<span class="blue-text">EXAMPLE:</span>
''ERBB2''
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|<span class="blue-text">EXAMPLE:</span>
Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.
|-
|
|
|
|
|
|
|
|}
 
{| class="wikitable sortable"
|-
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
!Diagnostic Significance (Yes, No or Unknown)<ref name=":2">Yabe M, Miranda RN, Medeiros LJ. Hepatosplenic T-cell Lymphoma: a review of clinicopathologic features, pathogenesis, and prognostic factors. ''Hum Pathol''. 2018;74:5‐16. doi:10.1016/j.humpath.2018.01.005</ref><ref name=":4">McKinney, M., Moffitt, A.B., Gaulard, P., Travert, M., De Leval, L., Nicolae, A., Raffeld, M., Jaffe, E.S., Pittaluga, S., Xi, L. and Heavican, T., 2017. The genetic basis of hepatosplenic T-cell lymphoma. ''Cancer discovery'', ''7''(4), pp.369-379.</ref>
!Prognostic Significance (Yes, No or Unknown)<ref name=":2" /><ref name=":4" />
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|7q
|Gain
|Gain
|
|7q, chr7
|Constant loss of 7p22.1p14.1
|Unknown
Gain of 7q22.11q31.1
|D, P
|Yes
|Yes
|No
|No
|Considered a primary aberration<ref name=":2" />, seen in 40-70% of cases<ref name=":1">{{Cite journal|title=Hepatosplenic T-cell lymphoma. In: WHO Classification of Tumours Editorial Board. Haematolymphoid tumours [Internet]|url=https://tumourclassification.iarc.who.int/chaptercontent/63/229|displayauthors=1|last=Medeiros|first=Jeffrey|date=2024|journal=WHO classification of tumours series, 5th ed.|volume=vol. 11|pages=|via=Lyon (France): International Agency for Research on Cancer}}</ref>
|Considered a primary aberration<ref name=":2">Yabe M, Miranda RN, Medeiros LJ. Hepatosplenic T-cell Lymphoma: a review of clinicopathologic features, pathogenesis, and prognostic factors. ''Hum Pathol''. 2018;74:5‐16. doi:10.1016/j.humpath.2018.01.005</ref>, seen in 40-70% of cases<ref name=":1">{{Cite journal|displayauthors=1|last=Medeiros|first=Jeffrey|date=2024|title=Hepatosplenic T-cell lymphoma. In: WHO Classification of Tumours Editorial Board. Haematolymphoid tumours [Internet]|url=https://tumourclassification.iarc.who.int/chaptercontent/63/229|journal=WHO classification of tumours series, 5th ed.|volume=vol. 11|pages=|via=Lyon (France): International Agency for Research on Cancer}}</ref>
|-
|-
|8
|8
|Gain (trisomy)
|Gain (trisomy)
|
|Chr8
|Chr8
|Yes
|Unknown
|Yes
|D, P
|No
|No
|Considered a secondary aberration<ref name=":2" />, seen in 10-50% of cases<ref name=":1" />
|Considered a secondary aberration<ref name=":2" />, seen in 10-50% of cases<ref name=":1" />
Line 156: Line 81:
|Y
|Y
|Loss
|Loss
|
|ChrY
|ChrY
|No
|Unknown
|No
|Unknown
|No
|No
|Seen in 20-25% of cases<ref name=":1" />
|Seen in 20-25% of cases<ref name=":1" />
|-
|-
|10q
|10
|Loss
|Loss
|
|10q, chr10
|Chr10
|Unknown
|No
|P
|No
|No
|No
|Seen in 10-20% of cases<ref name=":1" />
|Seen in 10-20% of cases<ref name=":1" />
|-
|-
|1q
|1
|Gain
|Gain
|
|1q, chr1
|Chr1
|Unknown
|No
|P
|No
|No
|No
|Seen in 10-15% of cases<ref name=":1" />
|Seen in 10-15% of cases<ref name=":1" />
|}<br />
|}
 
==Characteristic Chromosomal or Other Global Mutational Patterns==
==Characteristic Chromosomal or Other Global Mutational Patterns==
7q aberrations and trisomy 8 are considered specific for HSTL, but not sensitive<ref name=":2" />
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
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!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|Isochromosome 7q<ref name=":8">{{Cite journal|last=Wlodarska|first=Iwona|last2=Martin-Garcia|first2=Nadine|last3=Achten|first3=Ruth|last4=De Wolf-Peeters|first4=Chris|last5=Pauwels|first5=Patrick|last6=Tulliez|first6=Micheline|last7=de Mascarel|first7=Antoine|last8=Brière|first8=Josette|last9=Patey|first9=Martine|date=2002-03|title=Fluorescence in situ hybridization study of chromosome 7 aberrations in hepatosplenic T-cell lymphoma: isochromosome 7q as a common abnormality accumulating in forms with features of cytologic progression|url=https://pubmed.ncbi.nlm.nih.gov/11807981|journal=Genes, Chromosomes & Cancer|volume=33|issue=3|pages=243–251|doi=10.1002/gcc.10021|issn=1045-2257|pmid=11807981}}</ref> and chromosome 7 imbalances including ring chromosome 7.
Co-deletion of 1p and 18q
Can be seen in conjunction with trisomy 8
|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|Cases with chromosome 7 abnormalities show:
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
|<span class="blue-text">EXAMPLE:</span> D, P
|
|
|-
|<span class="blue-text">EXAMPLE:</span>
Microsatellite instability - hypermutated
|
|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
|<span class="blue-text">EXAMPLE:</span> P, T
|
|
|-
|
|
|
|
|
|
|}
 
*7q aberrations and trisomy 8 are considered specific for HSTL, but not sensitive<ref name=":2" />
 
{| class="wikitable sortable"
|-
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)<ref name=":2" /><ref name=":4" />
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|Isochromosome 7q<ref>{{Cite journal|last=Wlodarska|first=Iwona|last2=Martin-Garcia|first2=Nadine|last3=Achten|first3=Ruth|last4=De Wolf-Peeters|first4=Chris|last5=Pauwels|first5=Patrick|last6=Tulliez|first6=Micheline|last7=de Mascarel|first7=Antoine|last8=Brière|first8=Josette|last9=Patey|first9=Martine|date=2002-03|title=Fluorescence in situ hybridization study of chromosome 7 aberrations in hepatosplenic T-cell lymphoma: isochromosome 7q as a common abnormality accumulating in forms with features of cytologic progression|url=https://pubmed.ncbi.nlm.nih.gov/11807981|journal=Genes, Chromosomes & Cancer|volume=33|issue=3|pages=243–251|doi=10.1002/gcc.10021|issn=1045-2257|pmid=11807981}}</ref> and chromosome 7 imbalances including ring chromosome 7.
Cases with chromosome 7 abnormalities show:
 
*Constant loss of 7p22.1p14.1 (34.88 Mb; 3506316-38406226 bp)<ref name=":3">{{Cite journal|last=Finalet Ferreiro|first=Julio|last2=Rouhigharabaei|first2=Leila|last3=Urbankova|first3=Helena|last4=van der Krogt|first4=Jo-Anne|last5=Michaux|first5=Lucienne|last6=Shetty|first6=Shashirekha|last7=Krenacs|first7=Laszlo|last8=Tousseyn|first8=Thomas|last9=De Paepe|first9=Pascale|date=2014|title=Integrative genomic and transcriptomic analysis identified candidate genes implicated in the pathogenesis of hepatosplenic T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/25057852|journal=PloS One|volume=9|issue=7|pages=e102977|doi=10.1371/journal.pone.0102977|issn=1932-6203|pmc=4109958|pmid=25057852}}</ref>
*Constant loss of 7p22.1p14.1 (34.88 Mb; 3506316-38406226 bp)<ref name=":3">{{Cite journal|last=Finalet Ferreiro|first=Julio|last2=Rouhigharabaei|first2=Leila|last3=Urbankova|first3=Helena|last4=van der Krogt|first4=Jo-Anne|last5=Michaux|first5=Lucienne|last6=Shetty|first6=Shashirekha|last7=Krenacs|first7=Laszlo|last8=Tousseyn|first8=Thomas|last9=De Paepe|first9=Pascale|date=2014|title=Integrative genomic and transcriptomic analysis identified candidate genes implicated in the pathogenesis of hepatosplenic T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/25057852|journal=PloS One|volume=9|issue=7|pages=e102977|doi=10.1371/journal.pone.0102977|issn=1932-6203|pmc=4109958|pmid=25057852}}</ref>


*Gain of 7q22.11q31.1 (38.77 Mb; 86259620–124892276 bp)<ref name=":3" />
*Gain of 7q22.11q31.1 (38.77 Mb; 86259620–124892276 bp)<ref name=":3" />
 
|Common
Can be seen in conjunction with trisomy 8
|D, P
|Yes
|Yes
|No
|No
|See table under "Genomic Gain/Loss/LOH"
|See table under "Genomic Gain/Loss/LOH"
Line 248: Line 134:
|Loss of chromosome 10q  
|Loss of chromosome 10q  
Gain of chromosome 1q
Gain of chromosome 1q
|
|Recurrent
|P
|No
|No
|Yes
|occur in a significant minority of HSTL cases<ref name=":4">McKinney, M., Moffitt, A.B., Gaulard, P., Travert, M., De Leval, L., Nicolae, A., Raffeld, M., Jaffe, E.S., Pittaluga, S., Xi, L. and Heavican, T., 2017. The genetic basis of hepatosplenic T-cell lymphoma. ''Cancer discovery'', ''7''(4), pp.369-379.</ref>
|No
|}
|occur in a significant minority of HSTL cases<ref name=":4" />
|}<br />


==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>
Chromatin modifiers make up the most commonly mutated genes in HSTL, detected in 62% of cases. <ref name=":4" />
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
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!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''
<br />
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
|<span class="blue-text">EXAMPLE:</span> T
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
|<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
|-
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
<br />
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
|<span class="blue-text">EXAMPLE:</span> P
|
|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
|-
|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
|<span class="blue-text">EXAMPLE:</span> Activating mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
|<span class="blue-text">EXAMPLE:</span> T
|
|
|-
|
|
|
|
|
|
|
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
{| class="wikitable sortable"
|-
!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)<ref name=":4" />
!Prognostic Significance (Yes, No or Unknown)<ref name=":2" /><ref name=":4" />
!Therapeutic Significance (Yes, No or Unknown)<ref name=":2" /><ref>{{Cite journal|last=Pro|first=Barbara|last2=Allen|first2=Pamela|last3=Behdad|first3=Amir|date=2020-10-29|title=Hepatosplenic T-cell lymphoma: a rare but challenging entity|url=https://pubmed.ncbi.nlm.nih.gov/32756940|journal=Blood|volume=136|issue=18|pages=2018–2026|doi=10.1182/blood.2019004118|issn=1528-0020|pmc=7596851|pmid=32756940}}</ref>
!Notes
|-
|-
|''STAT3''; missense mutation
|''STAT3''; missense mutation
|missense mutation
|Oncogenic driver mutation
|Oncogenic driver mutation
|9%
|Recurrent
|
|T
|''STAT5b''; Only 1 reported case with both mutations present<ref name=":4" />
|No
|No
|No
|Yes
|Also seen in 40% of T-large granular lymphocyte leukemia<ref name=":2" />
|Also seen in 40% of T-large granular lymphocyte leukemia<ref name=":2" />
|-
|-
|''STAT5b''; missense mutation
|''STAT5b''; missense mutation
|missense mutation
|Oncogenic driver mutation
|Oncogenic driver mutation
|31%
|Common
|
|D, T
|''STAT3''; Only 1 reported case with both mutations present<ref name=":4" />
|Yes<ref name=":4" /><ref>{{Cite journal|last=Desmares|first=Anne|last2=Bouzy|first2=Simon|last3=Thonier|first3=Florian|last4=Goustille|first4=Julien|last5=Llamas-Gutierrez|first5=Francisco|last6=Genevieve|first6=Franck|last7=Cottin|first7=Laurane|last8=Baseggio|first8=Lucile|last9=Lemaire|first9=Pierre|date=2024-01-25|title=Hepatosplenic T-cell lymphoma displays an original oyster-shell cytological pattern and a distinct genomic profile from that of gamma-delta T-cell large granular lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/38268478|journal=Haematologica|doi=10.3324/haematol.2023.283856|issn=1592-8721|pmid=38268478}}</ref>
|No
|No
|Yes
|Highest functional potency: ''STAT5B'' N642H and V712E mutations<ref name=":2" />
|Highest functional potency: ''STAT5B'' N642H and V712E mutations<ref name=":2" />




One study showed increased CD56 expression with ''STAT5b''<ref>{{Cite journal|last=Nicolae|first=A.|last2=Xi|first2=L.|last3=Pittaluga|first3=S.|last4=Abdullaev|first4=Z.|last5=Pack|first5=S. D.|last6=Chen|first6=J.|last7=Waldmann|first7=T. A.|last8=Jaffe|first8=E. S.|last9=Raffeld|first9=M.|date=2014-11|title=Frequent STAT5B mutations in γδ hepatosplenic T-cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/24947020|journal=Leukemia|volume=28|issue=11|pages=2244–2248|doi=10.1038/leu.2014.200|issn=1476-5551|pmc=7701980|pmid=24947020}}</ref>
One study showed increased CD56 expression with ''STAT5b''<ref name=":9">{{Cite journal|last=Nicolae|first=A.|last2=Xi|first2=L.|last3=Pittaluga|first3=S.|last4=Abdullaev|first4=Z.|last5=Pack|first5=S. D.|last6=Chen|first6=J.|last7=Waldmann|first7=T. A.|last8=Jaffe|first8=E. S.|last9=Raffeld|first9=M.|date=2014-11|title=Frequent STAT5B mutations in γδ hepatosplenic T-cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/24947020|journal=Leukemia|volume=28|issue=11|pages=2244–2248|doi=10.1038/leu.2014.200|issn=1476-5551|pmc=7701980|pmid=24947020}}</ref>




Line 335: Line 174:
|-
|-
|''PIK3CD''
|''PIK3CD''
|Activating mutations
|Activate signaling
|Activate signaling
pathways important to cell survival<ref name=":4" />
pathways important to cell survival<ref name=":4" />
|9%
|Recurrent
|
|T
|
|No
|No
|No
|Yes
|
|
|-
|-
|''SETD2''; biallelic LOF
|''SETD2''; biallelic LOF
|biallelic LOF
|Tumor suppressor gene, chromatin modifier*<ref name=":4" />
|Tumor suppressor gene, chromatin modifier*<ref name=":4" />
|25%
|Common
|
|D, T
|
|Yes
|No
|No
|Yes
|''SET2–RPB1'' interacting domain (SRI) domain ( 31 ) at the COOH-terminus of the SETD2 protein product
|''SET2–RPB1'' interacting domain (SRI) domain ( 31 ) at the COOH-terminus of the SETD2 protein product


Line 362: Line 197:
|-
|-
|''INO80''
|''INO80''
|
|Chromatin modifier*
|Chromatin modifier*
|21%
|Common
|
|D, P, T
|
|No
|Yes
|Yes<ref name=":2" />
|Yes
|
|
|-
|-
|''ARID1B''
|''ARID1B''
|
|Chromatin modifier*
|Chromatin modifier*
|19%
|Recurrent
|
|Unknown
|
|No
|No
|No
|No
|
|
|-
|-
|''TET3''
|''TET3''
|
|Chromatin modifier*
|Chromatin modifier*
|15%
|Recurrent
|
|D, T
|
|Yes
|No
|No
|Yes
|
|
|-
|-
|''SMARCA2''
|''SMARCA2''
|
|Chromatin modifier*
|Chromatin modifier*
|10%
|Recurrent
|
|Unknown
|
|No
|No
|No
|No
|
|
|}
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
<nowiki>*</nowiki>Chromatin modifiers make up the most commonly mutated genes in HSTL, detected in 62% of cases. <ref name=":4" />
 
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 conten


==Epigenomic Alterations==
==Epigenomic Alterations==
Line 485: Line 309:
<nowiki>*</nowiki>''RHOA'' mutations predominantly favor Peripheral T-cell lymphomas, not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL)<ref name=":4" />  
<nowiki>*</nowiki>''RHOA'' mutations predominantly favor Peripheral T-cell lymphomas, not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL)<ref name=":4" />  


''**SyK'' expression was seen one study, which is not typical for normal T-cells<ref name=":5" />
''**SyK'' expression was seen one study, which is not typical for normal T-cells<ref name=":5" /> ''Syk'' is a protein tyrosine kinase usually involved in B-cell receptor signaling<ref name=":5" />
 
*''Syk'' is a protein tyrosine kinase usually involved in B-cell receptor signaling<ref name=":5" />


==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==


Clinical, morphologic, and immunophenotypic features are sufficient for diagnosis in most cases.  Cytogenetic testing could be used to support the diagnosis
Clinical, morphologic, and immunophenotypic features are sufficient for diagnosis in most cases.  Cytogenetic testing could be used to support the diagnosis.


*Karyotype may show trisomy 8, if present
*Karyotype may show trisomy 8, if present
Line 503: Line 325:


==Additional Information==
==Additional Information==
This disease is <u>defined/characterized</u> as detailed below:
HSTL is an aggressive subtype of extranodal, peripheral T-cell lymphoma with a poor response to therapy and an overall poor prognosis. This lymphoma is characterized by sinusoidal infiltration of the liver, spleen and often bone marrow, and uncommonly lymph nodes by cytotoxic T-cells that most commonly express the γδ T-cell receptor. Less commonly, this lymphoma can consist of a proliferation of αβ expressing cytotoxic T-cells <ref name=":0">Medeiros LJ, O'Malley DP, Caraway NP, Vega F, Elenitoba-Johnson KS, Lim MS: AFIP Atlas of Tumor Pathology. Washington, DC: American Registry of Pathology, 2017.</ref><ref name=":1" /><ref name=":2" />. Most cases occur de novo, with a subset of approximately 20-30% occurring in the setting of iatrogenic immunosuppression <ref name=":2" />.
 
Aggressive subtype of peripheral T-cell lymphoma. HSTL is an extranodal T-cell lymphoma that is known to have a poor response to therapy and an overall poor prognosis. This lymphoma is characterized by sinusoidal infiltration of the liver, spleen and often bone marrow, and uncommonly lymph nodes by cytotoxic T-cells that most commonly express the γδ T-cell receptor. Less commonly, some patients may have a variant of this lymphoma that is associated with αβ expressing cytotoxic T-cells <ref name=":0">Medeiros LJ, O'Malley DP, Caraway NP, Vega F, Elenitoba-Johnson KS, Lim MS: AFIP Atlas of Tumor Pathology. Washington, DC: American Registry of Pathology, 2017.</ref><ref name=":1" /><ref name=":2" />. Most cases occur de novo, with a subset of approximately 20-30% occurring in the setting of iatrogenic immunosuppression <ref name=":2" />.


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


*1.4-2% of peripheral T-cell lymphomas<ref name=":1" />
*1.4-2% of peripheral T-cell lymphomas<ref name=":1" />
*~75% are Classic γδ type<ref name=":1" />
*~75% are classic γδ type<ref name=":1" />
*Male predominance in gamma-delta subtype<ref name=":1" />
*Male predominance in γδ subtype<ref name=":1" />
*Median age ~ 35 years old<ref name=":2" />, 51% with age >60 years old<ref>{{Cite journal|last=Foss|first=Francine M.|last2=Horwitz|first2=Steven M.|last3=Civallero|first3=Monica|last4=Bellei|first4=Monica|last5=Marcheselli|first5=Luigi|last6=Kim|first6=Won Seog|last7=Cabrera|first7=Maria E.|last8=Dlouhy|first8=Ivan|last9=Nagler|first9=Arnon|date=2020-02|title=Incidence and outcomes of rare T cell lymphomas from the T Cell Project: hepatosplenic, enteropathy associated and peripheral gamma delta T cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/31709579|journal=American Journal of Hematology|volume=95|issue=2|pages=151–155|doi=10.1002/ajh.25674|issn=1096-8652|pmc=8025136|pmid=31709579}}</ref>
*Median age ~35 years old<ref name=":2" />, 51% with age >60 years old<ref>{{Cite journal|last=Foss|first=Francine M.|last2=Horwitz|first2=Steven M.|last3=Civallero|first3=Monica|last4=Bellei|first4=Monica|last5=Marcheselli|first5=Luigi|last6=Kim|first6=Won Seog|last7=Cabrera|first7=Maria E.|last8=Dlouhy|first8=Ivan|last9=Nagler|first9=Arnon|date=2020-02|title=Incidence and outcomes of rare T cell lymphomas from the T Cell Project: hepatosplenic, enteropathy associated and peripheral gamma delta T cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/31709579|journal=American Journal of Hematology|volume=95|issue=2|pages=151–155|doi=10.1002/ajh.25674|issn=1096-8652|pmc=8025136|pmid=31709579}}</ref>


The <u>clinical features</u> of this disease are detailed below:
<u>Clinical features:</u> Splenomegaly (most common symptom); B-symptoms (night sweats, fever, weight loss and fatigue); hepatomegaly; uncommonly lymphadenopathy; cytopenias (most commonly thrombocytopenia); elevated serum levels of B2M and LDH


Signs and symptoms - Splenomegaly (most common symptom); B-symptoms (night sweats, fever, weight loss and fatigue); Hepatomegaly; Lymphadenopathy (uncommon)
<u>Sites of involvement:</u> Spleen, liver, bone marrow, with or without leukemia involvement; uncommonly lymph nodes; rarely skin, usually in relapse cases


Laboratory findings - Cytopenias (most commonly thrombocytopenia); Elevated serum levels of B2M; Elevated serum levels of LDH
<u>Immunophenotype</u>:
 
The <u>sites of involvement</u> of this disease are detailed below:
 
*Spleen
*Liver
*Bone marrow
*Lymph node (uncommon)
*Skin (rarely, in relapse cases)
*With or without leukemic involvement
 
The <u>morphologic features</u> of this disease are detailed below:
 
*Typically shows a sinusoidal pattern
 
The <u>immunophenotype</u> of this disease is detailed below:


Positive (typically) - CD2, CD3, γδ T-cell receptor, TIA1, Granzyme M<ref name=":1" />
Positive (typically) - CD2, CD3, γδ T-cell receptor, TIA1, Granzyme M<ref name=":1" />
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==References==
==References==
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. 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. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references />
<references />
 
==Notes==
<nowiki>*</nowiki>''Citation of this Page'': Sargolzaeiaval F, Don M. “Hepatosplenic T-cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Hepatosplenic_T-cell_lymphoma</nowiki>.


<br />


==Notes==
<nowiki>*</nowiki>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 [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
<nowiki>*</nowiki>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 [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.


Prior Author(s):   
Prior Author(s): N/A  
 
       
<nowiki>*</nowiki>''Citation of this Page'': “Hepatosplenic T-cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Hepatosplenic_T-cell_lymphoma</nowiki>.
[[Category:HAEM5]]
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:DISEASE]]
[[Category:Diseases H]]
[[Category:Diseases H]]
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