HAEM5:Subcutaneous panniculitis-like T-cell lymphoma: Difference between revisions

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{{DISPLAYTITLE:Subcutaneous panniculitis-like T-cell lymphoma}}
{{DISPLAYTITLE:Subcutaneous panniculitis-like T-cell lymphoma}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
 
{{Under Construction}}
 
<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples). Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])</span>


==Primary Author(s)*==
==Primary Author(s)*==


Put your text here<span style="color:#0070C0"> (''Name and affiliation; example:'' Jane Smith, PhD, Institute of Genomics) </span>
Ian King, PhD  
 
__TOC__
 
==Cancer Category / Type==
 
Put your text here
 
==Cancer Sub-Classification / Subtype==
 
Put your text here
 
==Definition / Description of Disease==
 
Put your text here <span style="color:#0070C0">(''Instructions: Brief description of approximately one paragraph - include disease context relative to other WHO classification categories referring to the specific WHO book pages, diagnostic criteria if applicable, and differential diagnosis if applicable'') </span>
 
==Synonyms / Terminology==


Put your text here <span style="color:#0070C0">(''Instructions: Include currently used terms and major historical ones, adding “(historical)” after the latter.'') </span>
Katelyn Swanson, DO 
==WHO Classification of Disease==


==Epidemiology / Prevalence==
Put your text here
==Clinical Features==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
{| class="wikitable"
{| class="wikitable"
|'''Signs and Symptoms'''
!Structure
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
!Disease
 
EXAMPLE B-symptoms (weight loss, fever, night sweats)
 
EXAMPLE Fatigue
 
EXAMPLE Lymphadenopathy (uncommon)
|-
|-
|'''Laboratory Findings'''
|Book
|EXAMPLE Cytopenias
|Haematolymphoid Tumours (5th ed.)
 
EXAMPLE Lymphocytosis (low level)
|}
 
==Sites of Involvement==
 
Put your text here <span style="color:#0070C0">(''Instruction: Indicate physical sites; Example: nodal, extranodal, bone marrow'') </span>
 
==Morphologic Features==
 
Put your text here
 
==Immunophenotype==
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
 
{| class="wikitable sortable"
|-
|-
!Finding!!Marker
|Category
|T-cell and NK-cell lymphoid proliferations and lymphomas
|-
|-
|Positive (universal)||EXAMPLE CD1
|Family
|Mature T-cell and NK-cell neoplasms
|-
|-
|Positive (subset)||EXAMPLE CD2
|Type
|Primary cutaneous T-cell lymphoid proliferations and lymphomas
|-
|-
|Negative (universal)||EXAMPLE CD3
|Subtype(s)
|-
|Subcutaneous panniculitis-like T-cell lymphoma
|Negative (subset)||EXAMPLE CD4
|}
|}


==Chromosomal Rearrangements (Gene Fusions)==
==Related Terminology==


Put your text here and fill in the table
{| class="wikitable"
|+
|Acceptable
|N/A
|-
|Not Recommended
|N/A
|}


==Gene Rearrangements==
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
!Diagnostic Significance (Yes, No or Unknown)
!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Prognostic Significance (Yes, No or Unknown)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Therapeutic Significance (Yes, No or Unknown)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Notes
!Clinical Relevance Details/Other Notes
|-
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
|N/A
EXAMPLE 30% (add reference)
|N/A
|Yes
|N/A
|No
|N/A
|Yes
|N/A
|EXAMPLE
|N/A
 
|N/A
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
|N/A
|}
|}
==Individual Region Genomic Gain/Loss/LOH==
==Individual Region Genomic Gain / Loss / LOH==
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span>
 
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
!Diagnostic Significance (Yes, No or Unknown)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Prognostic Significance (Yes, No or Unknown)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Therapeutic Significance (Yes, No or Unknown)
!Clinical Relevance Details/Other Notes
!Notes
|-
|-
|EXAMPLE
|N/A
 
|N/A
7
|N/A
|EXAMPLE Loss
|N/A
|EXAMPLE
|N/A
 
|N/A
chr7:1- 159,335,973 [hg38]
|
|EXAMPLE
 
chr7
|Yes
|Yes
|No
|EXAMPLE
 
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 reference).
|-
|EXAMPLE
 
8
|EXAMPLE Gain
|EXAMPLE
 
chr8:1-145,138,636 [hg38]
|EXAMPLE
 
chr8
|No
|No
|No
|EXAMPLE
 
Common recurrent secondary finding for t(8;21) (add reference).
|}
|}
==Characteristic Chromosomal Patterns==
==Characteristic Chromosomal or Other Global Mutational Patterns==
 
Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis'')</span>
 
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosomal Pattern
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Molecular Pathogenesis
!Prognostic Significance (Yes, No or Unknown)
!Prevalence -
!Therapeutic Significance (Yes, No or Unknown)
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Notes
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|EXAMPLE
|N/A
 
|N/A
Co-deletion of 1p and 18q
|N/A
|Yes
|N/A
|No
|N/A
|No
|N/A
|EXAMPLE:
 
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|}
|}
==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 and common as well either disease defining and/or clinically significant. Can include references 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.'') </span>
 
{| 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!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence: Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!'''Diagnostic Significance (Yes, No or Unknown)'''
!Diagnostic, Prognostic, and Therapeutic Significance
!Prognostic Significance (Yes, No or Unknown)
D, P, T  
!Therapeutic Significance (Yes, No or Unknown)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Notes
!Clinical Relevance Details/Other Notes
|-
|-
|EXAMPLE: TP53; Variable LOF mutations
|''HAVCR2''
 
EXAMPLE:
 
EGFR; Exon 20 mutations
 
EXAMPLE: BRAF; Activating mutations
|EXAMPLE: TSG
|EXAMPLE: 20% (COSMIC)
 
EXAMPLE: 30% (add Reference)
|EXAMPLE: IDH1 R123H
|EXAMPLE: EGFR amplification
|
|
|
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
<br />
|}
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 content.


|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
|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>
''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.
==Epigenomic Alterations==
==Epigenomic Alterations==
 
None currently identified.
Put your text here
 
==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
|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" />,
|EXAMPLE: MAPK signaling
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" />,
|EXAMPLE: Increased cell growth and proliferation
 
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" />
|Unregulated cell division
|-
|TSC1<ref name=":0" /><ref name=":2" />, TSC2<ref name=":0" /><ref name=":2" />, MTOR<ref name=":0" /><ref name=":2" />, PIK3CB<ref name=":0" /><ref name=":2" />, PIK3CA<ref name=":0" /><ref name=":2" />, PIK3CD<ref name=":0" /><ref name=":2" />, AKT2<ref name=":2" />
|PI3K/AKT/mTOR pathway<ref name=":0" /><ref name=":2">{{Cite journal|last=Li|first=Zhaoming|last2=Lu|first2=Lisha|last3=Zhou|first3=Zhiyuan|last4=Xue|first4=Weili|last5=Wang|first5=Yingjun|last6=Jin|first6=Mengyuan|last7=Qiu|first7=Yajuan|last8=Sun|first8=Wei|last9=Fu|first9=Xuefei|date=2018-05|title=Recurrent mutations in epigenetic modifiers and the PI3K/AKT/mTOR pathway in subcutaneous panniculitis-like T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/28294301|journal=British Journal of Haematology|volume=181|issue=3|pages=406–410|doi=10.1111/bjh.14611|issn=1365-2141|pmid=28294301}}</ref>
|Increased cell growth and proliferation
|-
|''IL7R''<ref name=":0" /><ref name=":2" />'', JAK3''<ref name=":0" /><ref name=":2" /><ref name=":4" />'', STAT3''<ref name=":0" /><ref name=":2" />'', PIAS3''<ref name=":4" />
|JAK3/STAT pathway<ref name=":0" /><ref name=":2" />
|Unregulated cell division
|-
|-
|EXAMPLE: CDKN2A; Inactivating mutations
|TP53<ref name=":2" />
|EXAMPLE: Cell cycle regulation
|Tumor suppression<ref name=":2" />
|EXAMPLE: Unregulated cell division
|Increased cell growth and proliferation
|-
|-
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
|NAV3<ref name=":0" /><ref name=":2" /><ref name=":4" />
|EXAMPLE:  Histone modification, chromatin remodeling
|Microtubule activity and tumor suppression<ref name=":4" />
|EXAMPLE:  Abnormal gene expression program
|Increased cell growth and proliferation
|}
|}
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==
'''Molecular Testing to detect detect clonal T-cell receptor (TCR) beta and/or gamma gene rearrangements:'''


Put your text here
# Polymerase Chain Reaction (PCR) fragment analysis '''(major diagnostic criteria)'''<ref name=":6" />


==Familial Forms==
'''Molecular Genetic Testing for HAVCR2 variants:'''


Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
# 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<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==
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" />.


Put your text here
''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" />.


==Links==
==Links==


Put your text placeholder here (or anywhere appropriate on the page) and use the "Link" icon at the top of the page <span style="color:#0070C0">(''Instructions: Once you have a text placeholder entered to which you want to add a link, highlight that text, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address including the "<nowiki>http://www</nowiki>." portion.'')</span>
N/A


==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 on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''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''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />
<references />
 
==Notes==
'''EXAMPLE Book'''
<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.


#Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p129-171.
Prior Author(s): N/A


==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 CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
<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:

  1. Polymerase Chain Reaction (PCR) fragment analysis (major diagnostic criteria)[6]

Molecular Genetic Testing for HAVCR2 variants:

  1. Next generation sequencing (NGS) - whole exome sequencing and whole genome sequencing.
  2. Sanger sequencing - to confirm or detect HAVCR2 mutations.
  3. 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. ↑ 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. ↑ 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. ↑ 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. ↑ 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. ↑ 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. ↑ 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)
  7. ↑ 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).
  8. ↑ 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. ↑ 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.

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