Line 26: |
Line 26: |
| ==Definition / Description of Disease== | | ==Definition / Description of Disease== |
| | | |
− | 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">{{Cite journal|title=BlueBooksOnline|url=https://tumourclassification.iarc.who.int/chaptercontent/63/229}}</ref><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>. 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">{{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><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>. Most cases occur de novo, with a subset of approximately 20-30% occurring in the setting of iatrogenic immunosuppression <ref name=":2" />. |
| | | |
| ==Synonyms / Terminology== | | ==Synonyms / Terminology== |
Line 34: |
Line 34: |
| ==Epidemiology / Prevalence== | | ==Epidemiology / Prevalence== |
| | | |
− | * 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 gamma-delta 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> |
| | | |
| ==Clinical Features== | | ==Clinical Features== |
Line 82: |
Line 82: |
| ==Chromosomal Rearrangements (Gene Fusions)== | | ==Chromosomal Rearrangements (Gene Fusions)== |
| | | |
− | * No known chromosomal rearrangements at this time | + | *No known chromosomal rearrangements at this time |
| | | |
| ==Individual Region Genomic Gain / Loss / LOH== | | ==Individual Region Genomic Gain / Loss / LOH== |
Line 141: |
Line 141: |
| ==Characteristic Chromosomal Patterns== | | ==Characteristic Chromosomal Patterns== |
| | | |
− | * 7q aberrations and trisomy 8 are considered specific for HSTL, but not sensitive<ref name=":2" /> | + | *7q aberrations and trisomy 8 are considered specific for HSTL, but not sensitive<ref name=":2" /> |
| | | |
| {| class="wikitable sortable" | | {| class="wikitable sortable" |
Line 154: |
Line 154: |
| Cases with chromosome 7 abnormalities show: | | 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" /> Can be seen in conjunction with trisomy 8 | + | *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 | | Can be seen in conjunction with trisomy 8 |
Line 163: |
Line 163: |
| |No | | |No |
| | | | | |
− | * See table under "Genomic Gain/Loss/LOH" | + | *See table under "Genomic Gain/Loss/LOH" |
| | | |
| <br /> | | <br /> |
| | | |
− | * Cases without diagnostic detection of i(7q) or trisomy 8, often have detection of these abnormalities at the time of relapse or disease progression<ref name=":2" /> | + | *Cases without diagnostic detection of i(7q) or trisomy 8, often have detection of these abnormalities at the time of relapse or disease progression<ref name=":2" /> |
| |- | | |- |
| |Loss of chromosome 10q and gain of chromosome 1q | | |Loss of chromosome 10q and gain of chromosome 1q |
Line 174: |
Line 174: |
| |No | | |No |
| | | | | |
− | * occur in a significant minority of HSTL cases<ref name=":4" /> | + | *occur in a significant minority of HSTL cases<ref name=":4" /> |
| |}<br /> | | |}<br /> |
| ==Gene Mutations (SNV / INDEL)== | | ==Gene Mutations (SNV / INDEL)== |
Line 205: |
Line 205: |
| |Yes | | |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>{{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 |
Line 234: |
Line 234: |
| |Yes | | |Yes |
| | | | | |
− | * Most frequently silenced gene and most frequent mutated chromatin modifier in HSTL<ref name=":4" /> | + | *Most frequently silenced gene and most frequent mutated chromatin modifier in HSTL<ref name=":4" /> |
| | | |
− | * More than 44% of patients had more than 1 mutation in SETD2<ref name=":2" /> | + | *More than 44% of patients had more than 1 mutation in SETD2<ref name=":2" /> |
| |- | | |- |
| |INO80 | | |INO80 |
Line 291: |
Line 291: |
| ****Note: This finding is not specific to HSTL and can be seen in other T-cell lymphomas<ref name=":6" /> | | ****Note: This finding is not specific to HSTL and can be seen in other T-cell lymphomas<ref name=":6" /> |
| | | |
− | * A single study has shown use of IFNα2c therapy-induced changes in CpG methylation<ref name=":7">{{Cite journal|last=Bhat|first=Jaydeep|last2=Bergmann|first2=Anke K.|last3=Waschina|first3=Silvio|last4=Nerl|first4=Christoph|last5=Kaleta|first5=Christoph|last6=Siebert|first6=Reiner|last7=Ammerpohl|first7=Ole|last8=Kabelitz|first8=Dieter|date=2021-05|title=DNA methylation profile of a hepatosplenic gamma/delta T-cell lymphoma patient associated with response to interferon-α therapy|url=https://pubmed.ncbi.nlm.nih.gov/32820235|journal=Cellular & Molecular Immunology|volume=18|issue=5|pages=1332–1335|doi=10.1038/s41423-020-0518-4|issn=2042-0226|pmc=8093208|pmid=32820235}}</ref> | + | *A single study has shown use of IFNα2c therapy-induced changes in CpG methylation<ref name=":7">{{Cite journal|last=Bhat|first=Jaydeep|last2=Bergmann|first2=Anke K.|last3=Waschina|first3=Silvio|last4=Nerl|first4=Christoph|last5=Kaleta|first5=Christoph|last6=Siebert|first6=Reiner|last7=Ammerpohl|first7=Ole|last8=Kabelitz|first8=Dieter|date=2021-05|title=DNA methylation profile of a hepatosplenic gamma/delta T-cell lymphoma patient associated with response to interferon-α therapy|url=https://pubmed.ncbi.nlm.nih.gov/32820235|journal=Cellular & Molecular Immunology|volume=18|issue=5|pages=1332–1335|doi=10.1038/s41423-020-0518-4|issn=2042-0226|pmc=8093208|pmid=32820235}}</ref> |
− | ** CpG methylation changes have the potential to serve as biomarkers of drug responses and/or disease progression<ref name=":7" /> | + | **CpG methylation changes have the potential to serve as biomarkers of drug responses and/or disease progression<ref name=":7" /> |
| | | |
| ==Genes and Main Pathways Involved== | | ==Genes and Main Pathways Involved== |
Line 349: |
Line 349: |
| ''*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== |