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 (WHO Classification, 5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
{{Under Construction}}
<span style="color:#0070C0">(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], 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); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. 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)*==


Ian King, PhD


Put your text here<span style="color:#0070C0"> (''<span class="blue-text">EXAMPLE:</span>'' Jane Smith, PhD) </span>
Katelyn Swanson, DO 
==WHO Classification of Disease==
==WHO Classification of Disease==


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==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)*
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|-
|Other Classification
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|}
<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==


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==Gene Rearrangements==
==Gene Rearrangements==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
{| 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> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
|N/A
|<span class="blue-text">EXAMPLE:</span> Common (CML)
|N/A
|<span class="blue-text">EXAMPLE:</span> D, P, T
|N/A
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
|N/A
|<span class="blue-text">EXAMPLE:</span>
|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). BCR::ABL1 is generally favorable in CML (add reference).
|N/A
|-
|N/A
|<span class="blue-text">EXAMPLE:</span> ''CIC''
|N/A
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
|<span class="blue-text">EXAMPLE:</span> D
|
|<span class="blue-text">EXAMPLE:</span>
 
''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
|-
|<span class="blue-text">EXAMPLE:</span> ''ALK''
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
 
 
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
|<span class="blue-text">EXAMPLE:</span> T
|
|<span class="blue-text">EXAMPLE:</span>
 
Both balanced and unbalanced forms are observed by FISH (add references).
|-
|<span class="blue-text">EXAMPLE:</span> ''ABL1''
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
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|-
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|}
==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 rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chr #!!'''Gain, Loss, Amp, LOH'''!!'''Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]'''!!'''Relevant Gene(s)'''
!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'''
!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
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|N/A
7
|N/A
|<span class="blue-text">EXAMPLE:</span> Loss
|N/A
|<span class="blue-text">EXAMPLE:</span>
|N/A
chr7
|N/A
|<span class="blue-text">EXAMPLE:</span>
|N/A
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.
|-
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|}
==Characteristic Chromosomal or Other Global Mutational Patterns==
==Characteristic Chromosomal or Other Global Mutational Patterns==
Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as 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; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosomal Pattern
!Chromosomal Pattern
!Molecular Pathogenesis
!Molecular Pathogenesis
!'''Prevalence -'''
!Prevalence -  
'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
!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
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|N/A
Co-deletion of 1p and 18q
|N/A
|<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).
|N/A
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
|N/A
|<span class="blue-text">EXAMPLE:</span> D, P
|N/A
|
|N/A
|
|-
|<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
|
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|-
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|}
|}
==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>
{| 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  '''
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
|-
|-
|<span class="blue-text">EXAMPLE:</span>''EGFR''
|''HAVCR2''


<br />
|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>
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
|Tumor suppressor
|<span class="blue-text">EXAMPLE:</span> Oncogene
|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" />
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
|P, T
|<span class="blue-text">EXAMPLE:</span> T
|Yes; NCCN guidelines suggest germline testing in certain circumstances
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
|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>
|<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).
''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" />
|<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.
|}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==
Put your text here
None currently identified.
==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''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" />,
|<span class="blue-text">EXAMPLE:</span> 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" />,
|<span class="blue-text">EXAMPLE:</span> 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
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
|''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" />  
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|JAK3/STAT pathway<ref name=":0" /><ref name=":2" />
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|Unregulated cell division
|-
|-
|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
|TP53<ref name=":2" />
|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
|Tumor suppression<ref name=":2" />
|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
|Increased cell growth and proliferation
|-
|-
|
|NAV3<ref name=":0" /><ref name=":2" /><ref name=":4" />
|
|Microtubule activity and tumor suppression<ref name=":4" />
|
|Increased cell growth and proliferation
|}
|}
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==
Put your text here <span style="color:#0070C0">(''Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.'')</span>
'''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" />
 
'''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<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==
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>
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==
Put your text here
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" /> A major diagnostic criteria for is protein expression of TCRαβ and absence of TCRγδ <ref name=":6" />.
 
==Links==
==Links==


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==References==
==References==
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<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:

  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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