Changes

*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" />

Can be seen in conjunction with trisomy 8

Can be seen in conjunction with trisomy 8

!Notes

!Notes

|-

|-

|STAT3; missense mutation

|''STAT3''; missense mutation

|Oncogenic driver mutation

|Oncogenic driver mutation

|9%

|9%

|

|

|STAT5b; Only 1 reported case with both mutations present<ref name=":4" />

|''STAT5b''; Only 1 reported case with both mutations present<ref name=":4" />

|No

|No

|No

|No

|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

|Oncogenic driver mutation

|Oncogenic driver mutation

|31%

|31%

|

|

|STAT3; Only 1 reported case with both mutations present<ref name=":4" />

|''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>

|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

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>{{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>

Also seen in ~2% of T-large granular lymphocyte leukemia<ref name=":2" />

Also seen in ~2% of T-large granular lymphocyte leukemia<ref name=":2" />

|-

|-

|PIK3CD

|''PIK3CD''

|Activate signaling

|Activate signaling

pathways important to cell survival<ref name=":4" />

pathways important to cell survival<ref name=":4" />

|

|

|-

|-

|SETD2; biallelic LOF

|''SETD2''; biallelic LOF

|Tumor suppressor gene, chromatin modifier*<ref name=":4" />

|Tumor suppressor gene, chromatin modifier*<ref name=":4" />

|25%

|25%

|No

|No

|Yes

|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

71% of cases showing at least one LOF mutation<ref name=":4" />, and more than 44% of patients with SETD2 mutations had more than 1 mutation detected<ref name=":2" />

71% of cases showing at least one LOF mutation<ref name=":4" />, and more than 44% of patients with ''SETD2'' mutations had more than 1 mutation detected<ref name=":2" />

|-

|-

|INO80

|''INO80''

|Chromatin modifier*

|Chromatin modifier*

|21%

|21%

|

|

|-

|-

|ARID1B

|''ARID1B''

|Chromatin modifier*

|Chromatin modifier*

|19%

|19%

|

|

|-

|-

|TET3

|''TET3''

|Chromatin modifier*

|Chromatin modifier*

|15%

|15%

|

|

|-

|-

|SMARCA2

|''SMARCA2''

|Chromatin modifier*

|Chromatin modifier*

|10%

|10%

{| class="wikitable sortable"

{| class="wikitable sortable"

|-

|-

!Gene; Genetic Alteration<ref name=":5" />!!Pathway<ref name=":5" />!!Pathophysiologic Outcome

!Gene; Genetic Alteration<ref name=":4" /><ref name=":5" />!!Pathway<ref name=":4" /><ref name=":5" />!!Pathophysiologic Outcome<ref name=":4" /><ref name=":5" />

|-

|-

|''KIRs'', ''KLR'', ''CD244'', and ''NCAM1'' overexpression

|''KIRs'', ''KLR'', ''CD244'', and ''NCAM1'' overexpression

|Increased inflammatory response due to enhanced leukocyte endothelial transmigration

|Increased inflammatory response due to enhanced leukocyte endothelial transmigration

|-

|-

|''SPRY2'', ''RHOB'', ''MAP4K3'', and ''SPRY1'' overexpression

|''SPRY2'', ''RHOB*'', ''MAP4K3'', and ''SPRY1'' overexpression

|Signal transduction

|Signal transduction

|Altered cellular growth, differentiation, and migration. Overactive signaling pathways could contribute to oncogenesis

|Altered cellular growth, differentiation, and migration. Overactive signaling pathways could contribute to oncogenesis

|Distribution and accumulation of neoplastic γδ cells in the spleen and bone marrow

|Distribution and accumulation of neoplastic γδ cells in the spleen and bone marrow

|-

|-

|''SYK*'' overexpression

|''SYK**'' overexpression

|Tyrosine kinase

|Tyrosine kinase

|Cell growth and survival of neoplastic HSTL cells

|Cell growth and survival of neoplastic HSTL cells

|Reduced inflammatory and immune responses

|Reduced inflammatory and immune responses

|}

|}

''*SyK'' expression was seen one study, which is not typical for normal T-cells<ref name=":5" />

<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'' 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" />

*FISH targeted isochromosome 7q and trisomy 8

*FISH targeted isochromosome 7q and trisomy 8

*Next generation sequencing to support mutations seen in HSTL including ''STAT3, STAT5B, PI3KCD,'' ''SETD2, INO80, TET3'', and ''STAT5B''<ref name=":5" />  

*Next generation sequencing to support mutations seen in HSTL including ''STAT3, STAT5B, PI3KCD,'' ''SETD2, INO80, TET3'', and ''STAT5B''<ref name=":5" />  

**Presence of RHOA mutation, can potentially exclude HSTL from the differential diagnosis<ref name=":5" />

**Presence of ''RHOA'' mutation, can potentially exclude HSTL from the differential diagnosis<ref name=":5" />

==Familial Forms==

==Familial Forms==