HAEM5:Subcutaneous panniculitis-like T-cell lymphoma: Difference between revisions
Jump to navigation
Jump to search
| [unchecked revision] | [checked revision] |
No edit summary |
|||
| Line 49: | Line 49: | ||
!Clinical Relevance Details/Other Notes | !Clinical Relevance Details/Other Notes | ||
|- | |- | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
|} | |} | ||
==Individual Region Genomic Gain/Loss/LOH== | ==Individual Region Genomic Gain/Loss/LOH== | ||
| Line 66: | Line 66: | ||
!Clinical Relevance Details/Other Notes | !Clinical Relevance Details/Other Notes | ||
|- | |- | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
| | | | ||
|} | |} | ||
| Line 85: | Line 85: | ||
!Clinical Relevance Details/Other Notes | !Clinical Relevance Details/Other Notes | ||
|- | |- | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
| | |N/A | ||
|} | |} | ||
==Gene Mutations (SNV/INDEL)== | ==Gene Mutations (SNV/INDEL)== | ||
{| 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 | ||
!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 | ||
|- | |- | ||
|HAVCR2 | |''HAVCR2'' | ||
|Specific missense loss of function <ref name=":1">{{Cite journal|last=Gayden|first=Tenzin|last2=Sepulveda|first2=Fernando E.|last3=Khuong-Quang|first3=Dong-Anh|last4=Pratt|first4=Jonathan|last5=Valera|first5=Elvis T.|last6=Garrigue|first6=Alexandrine|last7=Kelso|first7=Susan|last8=Sicheri|first8=Frank|last9=Mikael|first9=Leonie G.|date=2018-12|title=Germline HAVCR2 mutations altering TIM-3 characterize subcutaneous panniculitis-like T cell lymphomas with hemophagocytic lymphohistiocytic syndrome|url=https://pubmed.ncbi.nlm.nih.gov/30374066|journal=Nature Genetics|volume=50|issue=12|pages=1650–1657|doi=10.1038/s41588-018-0251-4|issn=1546-1718|pmid=30374066}}</ref> | |Specific missense loss of function <ref name=":1">{{Cite journal|last=Gayden|first=Tenzin|last2=Sepulveda|first2=Fernando E.|last3=Khuong-Quang|first3=Dong-Anh|last4=Pratt|first4=Jonathan|last5=Valera|first5=Elvis T.|last6=Garrigue|first6=Alexandrine|last7=Kelso|first7=Susan|last8=Sicheri|first8=Frank|last9=Mikael|first9=Leonie G.|date=2018-12|title=Germline HAVCR2 mutations altering TIM-3 characterize subcutaneous panniculitis-like T cell lymphomas with hemophagocytic lymphohistiocytic syndrome|url=https://pubmed.ncbi.nlm.nih.gov/30374066|journal=Nature Genetics|volume=50|issue=12|pages=1650–1657|doi=10.1038/s41588-018-0251-4|issn=1546-1718|pmid=30374066}}</ref> | ||
|Tumor suppressor | |Tumor suppressor | ||
|Common >20%, <ref name=":0">{{Cite journal|last=Polprasert|first=Chantana|last2=Takeuchi|first2=Yasuhide|last3=Kakiuchi|first3=Nobuyuki|last4=Yoshida|first4=Kenichi|last5=Assanasen|first5=Thamathorn|last6=Sitthi|first6=Wimonmas|last7=Bunworasate|first7=Udomsak|last8=Pirunsarn|first8=Arunrat|last9=Wudhikarn|first9=Kitsada|date=2019-02-26|title=Frequent germline mutations of HAVCR2 in sporadic subcutaneous panniculitis-like T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/30792187|journal=Blood Advances|volume=3|issue=4|pages=588–595|doi=10.1182/bloodadvances.2018028340|issn=2473-9537|pmc=6391671|pmid=30792187}}</ref><ref name=":1" /> | |Common >20%, <ref name=":0">{{Cite journal|last=Polprasert|first=Chantana|last2=Takeuchi|first2=Yasuhide|last3=Kakiuchi|first3=Nobuyuki|last4=Yoshida|first4=Kenichi|last5=Assanasen|first5=Thamathorn|last6=Sitthi|first6=Wimonmas|last7=Bunworasate|first7=Udomsak|last8=Pirunsarn|first8=Arunrat|last9=Wudhikarn|first9=Kitsada|date=2019-02-26|title=Frequent germline mutations of HAVCR2 in sporadic subcutaneous panniculitis-like T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/30792187|journal=Blood Advances|volume=3|issue=4|pages=588–595|doi=10.1182/bloodadvances.2018028340|issn=2473-9537|pmc=6391671|pmid=30792187}}</ref><ref name=":1" /> | ||
|P, T | |||
|Yes; NCCN guidelines suggest germline testing in certain circumstances | |||
|May have prognostic and therapeutic significance in patients presenting with severe hemophagocytic syndromes.<ref name=":3">{{Cite journal|last=Sonigo|first=Gabrielle|last2=Battistella|first2=Maxime|last3=Beylot-Barry|first3=Marie|last4=Ingen-Housz-Oro|first4=Saskia|last5=Franck|first5=Nathalie|last6=Barete|first6=Stéphane|last7=Boulinguez|first7=Serge|last8=Dereure|first8=Olivier|last9=Bonnet|first9=Nathalie|date=2020-03-26|title=HAVCR2 mutations are associated with severe hemophagocytic syndrome in subcutaneous panniculitis-like T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/32005988|journal=Blood|volume=135|issue=13|pages=1058–1061|doi=10.1182/blood.2019003811|issn=1528-0020|pmid=32005988}}</ref> | |May have prognostic and therapeutic significance in patients presenting with severe hemophagocytic syndromes.<ref name=":3">{{Cite journal|last=Sonigo|first=Gabrielle|last2=Battistella|first2=Maxime|last3=Beylot-Barry|first3=Marie|last4=Ingen-Housz-Oro|first4=Saskia|last5=Franck|first5=Nathalie|last6=Barete|first6=Stéphane|last7=Boulinguez|first7=Serge|last8=Dereure|first8=Olivier|last9=Bonnet|first9=Nathalie|date=2020-03-26|title=HAVCR2 mutations are associated with severe hemophagocytic syndrome in subcutaneous panniculitis-like T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/32005988|journal=Blood|volume=135|issue=13|pages=1058–1061|doi=10.1182/blood.2019003811|issn=1528-0020|pmid=32005988}}</ref> | ||
''HAVCR2'' encodes for T-cell immunoglobulin and mucin domain protein 3 (TIM-3), a membrane modulator of immune response resulting in hemophagocytosis and uncontrolled activation of the innate immune system. | |||
Homozygous p.Y82C pathogenic variant is more common in East Asian populations<ref name=":1" /><ref name=":0" />, with p.T101I being a variant in South Asian (Thai) populations<ref name=":0" />, and p.I97M being more common in European and North African populations.<ref name=":1" /><ref name=":0" /><ref name=":3" /> | |||
|}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. | |}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. | ||
==Epigenomic Alterations== | ==Epigenomic Alterations== | ||
| Line 119: | Line 121: | ||
|ARID1B<ref name=":0" /><ref name=":2" />, SMARCA4<ref name=":0" /><ref name=":2" />, NCOR1<ref name=":0" /><ref name=":2" />, KMT2C<ref name=":2" />, KMT2D<ref name=":2" />, | |ARID1B<ref name=":0" /><ref name=":2" />, SMARCA4<ref name=":0" /><ref name=":2" />, NCOR1<ref name=":0" /><ref name=":2" />, KMT2C<ref name=":2" />, KMT2D<ref name=":2" />, | ||
DOTIL<ref name=":0" /><ref name=":2" />, CHD3<ref name=":0" /><ref name=":2" /><ref name=":4">{{Cite journal|last=Koh|first=Jiwon|last2=Jang|first2=Insoon|last3=Mun|first3=Seungchan|last4=Lee|first4=Cheol|last5=Cha|first5=Hee Jeong|last6=Oh|first6=Young Ha|last7=Kim|first7=Jin-Man|last8=Han|first8=Jae Ho|last9=Paik|first9=Jin Ho|date=2021-10-26|title=Genetic profiles of subcutaneous panniculitis-like T-cell lymphoma and clinicopathological impact of HAVCR2 mutations|url=https://pubmed.ncbi.nlm.nih.gov/34535012|journal=Blood Advances|volume=5|issue=20|pages=3919–3930|doi=10.1182/bloodadvances.2021004562|issn=2473-9537|pmc=8945616|pmid=34535012}}</ref>, CHD4<ref name=":0" /><ref name=":2" />, PBRM1<ref name=":2" />, CREBBP<ref name=":0" /><ref name=":2" />, | DOTIL<ref name=":0" /><ref name=":2" />, CHD3<ref name=":0" /><ref name=":2" /><ref name=":4">{{Cite journal|last=Koh|first=Jiwon|last2=Jang|first2=Insoon|last3=Mun|first3=Seungchan|last4=Lee|first4=Cheol|last5=Cha|first5=Hee Jeong|last6=Oh|first6=Young Ha|last7=Kim|first7=Jin-Man|last8=Han|first8=Jae Ho|last9=Paik|first9=Jin Ho|date=2021-10-26|title=Genetic profiles of subcutaneous panniculitis-like T-cell lymphoma and clinicopathological impact of HAVCR2 mutations|url=https://pubmed.ncbi.nlm.nih.gov/34535012|journal=Blood Advances|volume=5|issue=20|pages=3919–3930|doi=10.1182/bloodadvances.2021004562|issn=2473-9537|pmc=8945616|pmid=34535012}}</ref>, CHD4<ref name=":0" /><ref name=":2" />, PBRM1<ref name=":2" />, CREBBP<ref name=":0" /><ref name=":2" />, | ||
ASXL1<ref name=":0" /><ref name=":2" /><ref name=":4" />, MBD1<ref name=":2" />, KMT2B<ref name=":0" /><ref name=":2" />, HIST1H3J<ref name=":2" />, CDC27<ref name=":4" />, TET2<ref name=":0" /><ref name=":4" /> | ASXL1<ref name=":0" /><ref name=":2" /><ref name=":4" />, MBD1<ref name=":2" />, KMT2B<ref name=":0" /><ref name=":2" />, HIST1H3J<ref name=":2" />, CDC27<ref name=":4" />, TET2<ref name=":0" /><ref name=":4" /> | ||
|Epigenetic modifiers<ref name=":2" /><ref name=":4" /> | |Epigenetic modifiers<ref name=":2" /><ref name=":4" /> | ||
| Line 140: | Line 143: | ||
|} | |} | ||
==Genetic Diagnostic Testing Methods== | ==Genetic Diagnostic Testing Methods== | ||
'''Molecular Testing to detect detect clonal | '''Molecular Testing to detect detect clonal T-cell receptor (TCR) beta and/or gamma gene rearrangements:''' | ||
# Polymerase Chain Reaction (PCR) fragment analysis '''(major diagnostic criteria)'''<ref name=":6" /> | # Polymerase Chain Reaction (PCR) fragment analysis '''(major diagnostic criteria)'''<ref name=":6" /> | ||
| Line 146: | Line 149: | ||
'''Molecular Genetic Testing for HAVCR2 variants:''' | '''Molecular Genetic Testing for HAVCR2 variants:''' | ||
# Next generation sequencing (NGS)- whole exome sequencing and whole genome sequencing. | # Next generation sequencing (NGS) - whole exome sequencing and whole genome sequencing. | ||
# Sanger sequencing- to confirm or detect HAVCR2 mutations. | # Sanger sequencing - to confirm or detect ''HAVCR2'' mutations. | ||
# Droplet digital PCR (ddPCR): to confirm or detect presence of the HAVCR2 p.Y82C variant<ref>{{Cite journal|last=Cheng|first=Jinjun|last2=Xi|first2=Liqiang|last3=Jang|first3=Yoon|last4=Kim|first4=Jung|last5=Wang|first5=Hao-Wei|last6=Pittaluga|first6=Stefania|last7=Jaffe|first7=Elaine S.|last8=Raffeld|first8=Mark|date=2024-10-01|title=An investigation of germline variants of HAVCR2 in subcutaneous panniculitis-like T-cell lymphoma and related lesions in a North American population|url=https://pubmed.ncbi.nlm.nih.gov/38867583|journal=Haematologica|volume=109|issue=10|pages=3363–3367|doi=10.3324/haematol.2023.284738|issn=1592-8721|pmc=11443401|pmid=38867583}}</ref> | # Droplet digital PCR (ddPCR): to confirm or detect presence of the ''HAVCR2'' p.Y82C variant<ref>{{Cite journal|last=Cheng|first=Jinjun|last2=Xi|first2=Liqiang|last3=Jang|first3=Yoon|last4=Kim|first4=Jung|last5=Wang|first5=Hao-Wei|last6=Pittaluga|first6=Stefania|last7=Jaffe|first7=Elaine S.|last8=Raffeld|first8=Mark|date=2024-10-01|title=An investigation of germline variants of HAVCR2 in subcutaneous panniculitis-like T-cell lymphoma and related lesions in a North American population|url=https://pubmed.ncbi.nlm.nih.gov/38867583|journal=Haematologica|volume=109|issue=10|pages=3363–3367|doi=10.3324/haematol.2023.284738|issn=1592-8721|pmc=11443401|pmid=38867583}}</ref> | ||
==Familial Forms== | ==Familial Forms== | ||
Biallelic germline mutations in HAVCR2 are inherited in an autosomal recessive pattern predominantly in individuals with East Asian ancestry.<ref name=":1" /><ref name=":0" /><ref name=":4" /> | Biallelic germline mutations in ''HAVCR2'' are inherited in an autosomal recessive pattern predominantly in individuals with East Asian ancestry.<ref name=":1" /><ref name=":0" /><ref name=":4" /> | ||
==Additional Information== | ==Additional Information== | ||
Subcutaneous panniculitis like T-cell lymphoma may be triggered or associated with viral etiologies including human immunodeficiency virus (HIV)<ref name=":0" />; with one case being reported after vaccination for SarsCoV2<ref>{{Cite journal|last=Kreher|first=Margaret Ann|last2=Ahn|first2=John|last3=Werbel|first3=Tyler|last4=Motaparthi|first4=Kiran|date=2022-10|title=Subcutaneous panniculitis-like T-cell lymphoma after COVID-19 vaccination|url=https://pubmed.ncbi.nlm.nih.gov/35966352|journal=JAAD case reports|volume=28|pages=18–20|doi=10.1016/j.jdcr.2022.08.006|issn=2352-5126|pmc=9364717|pmid=35966352}}</ref>. Typically, this entity is Epstein-Barr virus negative; however, it is rarely detected in Asian populations<ref name=":5">{{Cite journal|last=Kong|first=Yun-yi|last2=Dai|first2=Bo|last3=Kong|first3=Jin-cheng|last4=Zhou|first4=Xiao-yan|last5=Lu|first5=Hong-fen|last6=Shen|first6=Lei|last7=Du|first7=Xiang|last8=Shi|first8=Da-ren|date=2008-10|title=Subcutaneous panniculitis-like T-cell lymphoma: a clinicopathologic, immunophenotypic, and molecular study of 22 Asian cases according to WHO-EORTC classification|url=https://pubmed.ncbi.nlm.nih.gov/18708940|journal=The American Journal of Surgical Pathology|volume=32|issue=10|pages=1495–1502|doi=10.1097/PAS.0b013e31817a9081|issn=1532-0979|pmid=18708940}}</ref>. Association with autoimmune conditions such as systemic lupus erythematous have also been reported<ref name=":0" />. | Subcutaneous panniculitis like T-cell lymphoma may be triggered or associated with viral etiologies including human immunodeficiency virus (HIV)<ref name=":0" />; with one case being reported after vaccination for SarsCoV2<ref>{{Cite journal|last=Kreher|first=Margaret Ann|last2=Ahn|first2=John|last3=Werbel|first3=Tyler|last4=Motaparthi|first4=Kiran|date=2022-10|title=Subcutaneous panniculitis-like T-cell lymphoma after COVID-19 vaccination|url=https://pubmed.ncbi.nlm.nih.gov/35966352|journal=JAAD case reports|volume=28|pages=18–20|doi=10.1016/j.jdcr.2022.08.006|issn=2352-5126|pmc=9364717|pmid=35966352}}</ref>. Typically, this entity is Epstein-Barr virus negative; however, it is rarely detected in Asian populations<ref name=":5">{{Cite journal|last=Kong|first=Yun-yi|last2=Dai|first2=Bo|last3=Kong|first3=Jin-cheng|last4=Zhou|first4=Xiao-yan|last5=Lu|first5=Hong-fen|last6=Shen|first6=Lei|last7=Du|first7=Xiang|last8=Shi|first8=Da-ren|date=2008-10|title=Subcutaneous panniculitis-like T-cell lymphoma: a clinicopathologic, immunophenotypic, and molecular study of 22 Asian cases according to WHO-EORTC classification|url=https://pubmed.ncbi.nlm.nih.gov/18708940|journal=The American Journal of Surgical Pathology|volume=32|issue=10|pages=1495–1502|doi=10.1097/PAS.0b013e31817a9081|issn=1532-0979|pmid=18708940}}</ref>. Association with autoimmune conditions such as systemic lupus erythematous have also been reported<ref name=":0" />. | ||
''Immunohistochemical profile'': Subcutaneous panniculitis like T-cell lymphoma is a rare cytotoxic (CD3+, CD4-, CD8+, granzyme B +) T-cell lymphoma with atypical T-cells infiltrating subcutaneous tissue and rimming adipocytes in a "lace-like" pattern<ref name=":5" /><ref name=":6">{{Cite journal|last=Parveen|first=Zahida|last2=Thompson|first2=Karen|date=2009-02|title=Subcutaneous panniculitis-like T-cell lymphoma: redefinition of diagnostic criteria in the recent World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/19195975|journal=Archives of Pathology & Laboratory Medicine|volume=133|issue=2|pages=303–308|doi=10.5858/133.2.303|issn=1543-2165|pmid=19195975}}</ref>. In one study, expression of CCR4 and FOXP3 was increased in tumor cells in sporadic cases with HAVCR2 wild-type genotypes.<ref name=":4" /> | ''Immunohistochemical profile'': Subcutaneous panniculitis like T-cell lymphoma is a rare cytotoxic (CD3+, CD4-, CD8+, granzyme B +) T-cell lymphoma with atypical T-cells infiltrating subcutaneous tissue and rimming adipocytes in a "lace-like" pattern<ref name=":5" /><ref name=":6">{{Cite journal|last=Parveen|first=Zahida|last2=Thompson|first2=Karen|date=2009-02|title=Subcutaneous panniculitis-like T-cell lymphoma: redefinition of diagnostic criteria in the recent World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/19195975|journal=Archives of Pathology & Laboratory Medicine|volume=133|issue=2|pages=303–308|doi=10.5858/133.2.303|issn=1543-2165|pmid=19195975}}</ref>. In one study, expression of CCR4 and FOXP3 was increased in tumor cells in sporadic cases with HAVCR2 wild-type genotypes.<ref name=":4" /> A major diagnostic criteria for is protein expression of TCRαβ and absence of TCRγδ <ref name=":6" />. | ||
A major diagnostic criteria for | |||
==Links== | ==Links== | ||
N/A | |||
==References== | ==References== | ||
<references /> | |||
==Notes== | ==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'': “Subcutaneous panniculitis-like T-cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Subcutaneous_panniculitis-like_T-cell_lymphoma</nowiki>. | <nowiki>*</nowiki>''Citation of this Page'': “Subcutaneous panniculitis-like T-cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Subcutaneous_panniculitis-like_T-cell_lymphoma</nowiki>. | ||
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases S]] | [[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases S]] | ||
Latest revision as of 16:33, 6 January 2026
Haematolymphoid Tumours (WHO Classification, 5th ed.)
Primary Author(s)*
Ian King, PhD
Katelyn Swanson, DO
WHO Classification of Disease
| Structure | Disease |
|---|---|
| Book | Haematolymphoid Tumours (5th ed.) |
| Category | T-cell and NK-cell lymphoid proliferations and lymphomas |
| Family | Mature T-cell and NK-cell neoplasms |
| Type | Primary cutaneous T-cell lymphoid proliferations and lymphomas |
| Subtype(s) | Subcutaneous panniculitis-like T-cell lymphoma |
Related Terminology
| Acceptable | N/A |
| Not Recommended | N/A |
Gene Rearrangements
| 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 |
|---|---|---|---|---|---|---|---|
| N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
Individual Region Genomic Gain/Loss/LOH
| 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 |
|---|---|---|---|---|---|---|
| N/A | N/A | N/A | N/A | N/A | N/A |
Characteristic Chromosomal or Other Global Mutational Patterns
| Chromosomal Pattern | 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 |
|---|---|---|---|---|---|
| N/A | N/A | N/A | N/A | N/A | N/A |
Gene Mutations (SNV/INDEL)
| Gene | Genetic Alteration | Tumor Suppressor Gene, Oncogene, Other | 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 |
|---|---|---|---|---|---|---|
| HAVCR2 | Specific missense loss of function [1] | Tumor suppressor | Common >20%, [2][1] | P, T | Yes; NCCN guidelines suggest germline testing in certain circumstances | May have prognostic and therapeutic significance in patients presenting with severe hemophagocytic syndromes.[3]
HAVCR2 encodes for T-cell immunoglobulin and mucin domain protein 3 (TIM-3), a membrane modulator of immune response resulting in hemophagocytosis and uncontrolled activation of the innate immune system. Homozygous p.Y82C pathogenic variant is more common in East Asian populations[1][2], with p.T101I being a variant in South Asian (Thai) populations[2], and p.I97M being more common in European and North African populations.[1][2][3] |
Note: A more extensive list of mutations can be found in cBioportal, COSMIC, and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
Epigenomic Alterations
None currently identified.
Genes and Main Pathways Involved
| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| ARID1B[2][4], SMARCA4[2][4], NCOR1[2][4], KMT2C[4], KMT2D[4],
DOTIL[2][4], CHD3[2][4][5], CHD4[2][4], PBRM1[4], CREBBP[2][4], ASXL1[2][4][5], MBD1[4], KMT2B[2][4], HIST1H3J[4], CDC27[5], TET2[2][5] |
Epigenetic modifiers[4][5] | Unregulated cell division |
| TSC1[2][4], TSC2[2][4], MTOR[2][4], PIK3CB[2][4], PIK3CA[2][4], PIK3CD[2][4], AKT2[4] | PI3K/AKT/mTOR pathway[2][4] | Increased cell growth and proliferation |
| IL7R[2][4], JAK3[2][4][5], STAT3[2][4], PIAS3[5] | JAK3/STAT pathway[2][4] | Unregulated cell division |
| TP53[4] | Tumor suppression[4] | Increased cell growth and proliferation |
| NAV3[2][4][5] | Microtubule activity and tumor suppression[5] | Increased cell growth and proliferation |
Genetic Diagnostic Testing Methods
Molecular Testing to detect detect clonal T-cell receptor (TCR) beta and/or gamma gene rearrangements:
- Polymerase Chain Reaction (PCR) fragment analysis (major diagnostic criteria)[6]
Molecular Genetic Testing for HAVCR2 variants:
- Next generation sequencing (NGS) - whole exome sequencing and whole genome sequencing.
- Sanger sequencing - to confirm or detect HAVCR2 mutations.
- Droplet digital PCR (ddPCR): to confirm or detect presence of the HAVCR2 p.Y82C variant[7]
Familial Forms
Biallelic germline mutations in HAVCR2 are inherited in an autosomal recessive pattern predominantly in individuals with East Asian ancestry.[1][2][5]
Additional Information
Subcutaneous panniculitis like T-cell lymphoma may be triggered or associated with viral etiologies including human immunodeficiency virus (HIV)[2]; with one case being reported after vaccination for SarsCoV2[8]. Typically, this entity is Epstein-Barr virus negative; however, it is rarely detected in Asian populations[9]. Association with autoimmune conditions such as systemic lupus erythematous have also been reported[2].
Immunohistochemical profile: Subcutaneous panniculitis like T-cell lymphoma is a rare cytotoxic (CD3+, CD4-, CD8+, granzyme B +) T-cell lymphoma with atypical T-cells infiltrating subcutaneous tissue and rimming adipocytes in a "lace-like" pattern[9][6]. In one study, expression of CCR4 and FOXP3 was increased in tumor cells in sporadic cases with HAVCR2 wild-type genotypes.[5] A major diagnostic criteria for is protein expression of TCRαβ and absence of TCRγδ [6].
Links
N/A
References
- ↑ 1.0 1.1 1.2 1.3 1.4 Gayden, Tenzin; et al. (2018-12). "Germline HAVCR2 mutations altering TIM-3 characterize subcutaneous panniculitis-like T cell lymphomas with hemophagocytic lymphohistiocytic syndrome". Nature Genetics. 50 (12): 1650–1657. doi:10.1038/s41588-018-0251-4. ISSN 1546-1718. PMID 30374066. Check date values in:
|date=(help) - ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 2.24 2.25 2.26 2.27 2.28 Polprasert, Chantana; et al. (2019-02-26). "Frequent germline mutations of HAVCR2 in sporadic subcutaneous panniculitis-like T-cell lymphoma". Blood Advances. 3 (4): 588–595. doi:10.1182/bloodadvances.2018028340. ISSN 2473-9537. PMC 6391671. PMID 30792187.
- ↑ 3.0 3.1 Sonigo, Gabrielle; et al. (2020-03-26). "HAVCR2 mutations are associated with severe hemophagocytic syndrome in subcutaneous panniculitis-like T-cell lymphoma". Blood. 135 (13): 1058–1061. doi:10.1182/blood.2019003811. ISSN 1528-0020. PMID 32005988 Check
|pmid=value (help). - ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 4.16 4.17 4.18 4.19 4.20 4.21 4.22 4.23 4.24 4.25 4.26 4.27 4.28 4.29 Li, Zhaoming; et al. (2018-05). "Recurrent mutations in epigenetic modifiers and the PI3K/AKT/mTOR pathway in subcutaneous panniculitis-like T-cell lymphoma". British Journal of Haematology. 181 (3): 406–410. doi:10.1111/bjh.14611. ISSN 1365-2141. PMID 28294301. Check date values in:
|date=(help) - ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 Koh, Jiwon; et al. (2021-10-26). "Genetic profiles of subcutaneous panniculitis-like T-cell lymphoma and clinicopathological impact of HAVCR2 mutations". Blood Advances. 5 (20): 3919–3930. doi:10.1182/bloodadvances.2021004562. ISSN 2473-9537. PMC 8945616 Check
|pmc=value (help). PMID 34535012 Check|pmid=value (help). - ↑ 6.0 6.1 6.2 Parveen, Zahida; et al. (2009-02). "Subcutaneous panniculitis-like T-cell lymphoma: redefinition of diagnostic criteria in the recent World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas". Archives of Pathology & Laboratory Medicine. 133 (2): 303–308. doi:10.5858/133.2.303. ISSN 1543-2165. PMID 19195975. Check date values in:
|date=(help) - ↑ Cheng, Jinjun; et al. (2024-10-01). "An investigation of germline variants of HAVCR2 in subcutaneous panniculitis-like T-cell lymphoma and related lesions in a North American population". Haematologica. 109 (10): 3363–3367. doi:10.3324/haematol.2023.284738. ISSN 1592-8721. PMC 11443401 Check
|pmc=value (help). PMID 38867583 Check|pmid=value (help). - ↑ Kreher, Margaret Ann; et al. (2022-10). "Subcutaneous panniculitis-like T-cell lymphoma after COVID-19 vaccination". JAAD case reports. 28: 18–20. doi:10.1016/j.jdcr.2022.08.006. ISSN 2352-5126. PMC 9364717 Check
|pmc=value (help). PMID 35966352 Check|pmid=value (help). Check date values in:|date=(help) - ↑ 9.0 9.1 Kong, Yun-yi; et al. (2008-10). "Subcutaneous panniculitis-like T-cell lymphoma: a clinicopathologic, immunophenotypic, and molecular study of 22 Asian cases according to WHO-EORTC classification". The American Journal of Surgical Pathology. 32 (10): 1495–1502. doi:10.1097/PAS.0b013e31817a9081. ISSN 1532-0979. PMID 18708940. Check date values in:
|date=(help)
Notes
*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 Associate Editor 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): N/A
*Citation of this Page: “Subcutaneous panniculitis-like T-cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 01/6/2026, https://ccga.io/index.php/HAEM5:Subcutaneous_panniculitis-like_T-cell_lymphoma.