Primary cutaneous gamma/delta T-cell lymphoma
Haematolymphoid Tumours (WHO Classification, 5th ed.)
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(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 HUGO-approved gene names and symbols (italicized when appropriate), 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); 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 Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support.)
Primary Author(s)*
Put your text here (EXAMPLE: Jane Smith, PhD)
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) | Primary cutaneous gamma/delta T-cell lymphoma |
Related Terminology
| Acceptable | N/A |
| Not Recommended | N/A |
Gene Rearrangements
Put your text here and fill in the table (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.)
| Gene / Fusion | Partner Gene (for fusion) | Genetic Alteration & Molecular Pathogenesis | Tumour Suppressor / Oncogene / Other | Prevalence* | D / P / T | Established clinical significance per guidelines? | Clinical relevance / Other notes | Reference (PubMed) |
| CDKN2A | — | Homozygous or biallelic deletion → loss of p16^INK4A/p14^ARF function (cell‑cycle control) | Tumour suppressor | Common (>20%) (~61% in cohort) (PubMed) | P | No | High‐frequency deletion, suggests aggressive biology and may be a prognostic marker | PMID 32286303 (PMC) |
| ARID1A | — | Deletion/truncating mutation → loss of chromatin‑remodelling function | Tumour suppressor | Recurrent (5‑20%) (~28%) (PMC) | Other / P | No | Indicates involvement of epigenetic/chromatin pathways in PCGDTCL | PMID 32286303 (PMC) |
| FAS | — | Focal or biallelic deletion → loss of apoptosis signalling via FAS‑FASL pathway | Tumour suppressor / apoptotic regulator | Recurrent (5‑20%) (~22%) (PMC) | Other / P | No | Loss of FAS may contribute to immune‐escape of malignant γδ T‑cells | PMID 32286303 (PMC) |
| PDCD1 | — | Deletion → loss of PD‑1 (immune‐checkpoint) regulatory function | Tumour suppressor / immune‑regulator | Recurrent (5‑20%) (~22%) (PMC) | Other / P | No | Suggests immune‐escape mechanism; potential implications for checkpoint therapy though unproven | PMID 32286303 (PMC) |
| STAT5B | — | Activating missense (e.g., N642H) → constitutive STAT5B signalling (JAK/STAT pathway) | Oncogene | Recurrent (5‑20%) (JAK/STAT mutations ~21%) (PubMed) | T / P | No | JAK/STAT pathway dependency; early data suggest JAK‐inhibitor sensitivity in analogous T‑cell neoplasms; investigational in PCGDTCL | PMID 25586472 (PubMed) |
| STAT3 | — | Activating missense → constitutive STAT3 signalling (JAK/STAT cascade) | Oncogene | Rare (<5%) to Recurrent (~5‑20%) (PubMed) | T / P | No | Part of JAK/STAT alterations; less frequent than STAT5B in PCGDTCL | PMID 25586472 (PubMed) |
| JAK3 | — | Activating mutation (e.g., R657W) → JAK3 tyrosine kinase activation (JAK/STAT pathway) | Oncogene | Rare (<5%) (PMC) | T | No | Supports JAK/STAT pathway involvement; therapeutic relevance remains investigational in this disease | PMID 32286303 (PMC) |
| KRAS | — | Activating hotspot mutations (e.g., G12D, Q61H) → RAS/MAPK pathway activation | Oncogene | Recurrent (5‑20%) (PubMed) | T / P | No | MAPK pathway potentially targetable; mutations associated with poorer outcome in the cohort studied | PMID 32286303 (PMC) |
| NRAS | — | Activating hotspot mutation → RAS/MAPK pathway activation | Oncogene | Rare (<5%) to Recurrent (~5‑20%) (PMC) | T / P | No | Part of same pathway as KRAS though less common | PMID 32286303 (PMC) |
| MYC | — | Activating missense mutation (e.g., P74L) → MYC pathway up‑regulation | Oncogene | Rare (<5%) (PMC) | P / T | No | MYC pathway involvement may contribute to more aggressive phenotype; direct targeting not yet established | PMID 32286303 (PMC) |
| MYCN | — | Activating mutation (e.g., G34R) → MYCN pathway activation | Oncogene | Rare (<5%) (PMC) | P / T | No | Highlights involvement of MYC family beyond MYC itself in PCGDTCL | PMID 32286303 (PMC) |
| Arm‑level chromosomal alterations (e.g., 9p, 18q deletions; 1q, 7q,15q gains) | — | Copy number loss or gain → altered gene dosage of tumour suppressors/oncogenes | Other / chromosomal alteration | Recurrent (5‑20%) (9p del ~22%, 18q del ~22%; 1q/7q/15q gains ~33‑39%) (PMC) | D / P | No | These structural changes suggest genomic instability and aggressive biology; may help risk stratification though not diagnostic per se | PMID 32286303 (PMC) |
| Fusion: FYN :: (probable partner TRAF3IP2) | TRAF3IP2 | Structural alteration – deletion/exon8 deletion → (in other T‑cell lymphomas) FYN::TRAF3IP2 fusion leading to SRC‑family kinase activation; in this PCGDTCL case FYN exon8 deletion noted (PubMed) | Oncogene / Other | Rare (<5%) (single case reported) | T | No | Very recently described; may represent novel driver/target; further cases needed | PMID 39412302 (PubMed) |
| Fusion: PCM1 :: JAK2 | PCM1 | Fusion → juxtaposition of dimerization domain of PCM1 with kinase domain of JAK2 → constitutive JAK2 activation | Oncogene | Rare (<5%) (single documented PCGDTCL case) (PubMed) | T | No | Known in other T‑cell and myeloid neoplasms; in PCGDTCL this double‐hit case had PCM1::JAK2 + TBL1XR1::TP63 fusion; patient refractory to JAK inhibitor | PMID 37308177 (PubMed) |
| Fusion: TBL1XR1 :: TP63 | TBL1XR1 | Fusion → truncation/overexpression of ΔNp63 form → oncogenic p63 signalling | Oncogene / Other | Rare (<5%) (same single case) (PubMed) | P / T | No | Associated with aggressive behaviour in T‑cell lymphomas; in the reported PCGDTCL case contributed to aggressive course and JAK inhibitor resistance | PMID 37308177 (PubMed) |
| 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 |
|---|---|---|---|---|---|---|---|
| EXAMPLE: ABL1 | EXAMPLE: BCR::ABL1 | EXAMPLE: The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1. | EXAMPLE: t(9;22)(q34;q11.2) | EXAMPLE: Common (CML) | EXAMPLE: D, P, T | EXAMPLE: Yes (WHO, NCCN) | EXAMPLE:
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). |
| EXAMPLE: CIC | EXAMPLE: CIC::DUX4 | EXAMPLE: 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. | EXAMPLE: t(4;19)(q25;q13) | EXAMPLE: Common (CIC-rearranged sarcoma) | EXAMPLE: D | EXAMPLE:
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). | |
| EXAMPLE: ALK | EXAMPLE: ELM4::ALK
|
EXAMPLE: 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. | EXAMPLE: N/A | EXAMPLE: Rare (Lung adenocarcinoma) | EXAMPLE: T | EXAMPLE:
Both balanced and unbalanced forms are observed by FISH (add references). | |
| EXAMPLE: ABL1 | EXAMPLE: N/A | EXAMPLE: 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. | EXAMPLE: N/A | EXAMPLE: Recurrent (IDH-wildtype Glioblastoma) | EXAMPLE: D, P, T | ||
Individual Region Genomic Gain/Loss/LOH
Put your text here and fill in the table (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.)
| 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 |
|---|---|---|---|---|---|---|
| EXAMPLE:
7 |
EXAMPLE: Loss | EXAMPLE:
chr7 |
EXAMPLE:
Unknown |
EXAMPLE: D, P | EXAMPLE: 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 references). |
| EXAMPLE:
8 |
EXAMPLE: Gain | EXAMPLE:
chr8 |
EXAMPLE:
Unknown |
EXAMPLE: D, P | EXAMPLE:
Common recurrent secondary finding for t(8;21) (add references). | |
| EXAMPLE:
17 |
EXAMPLE: Amp | EXAMPLE:
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb] |
EXAMPLE:
ERBB2 |
EXAMPLE: D, P, T | EXAMPLE:
Amplification of ERBB2 is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined. | |
Characteristic Chromosomal or Other Global Mutational Patterns
Put your text here and fill in the table (Instructions: 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.)
| 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 |
|---|---|---|---|---|---|
| EXAMPLE:
Co-deletion of 1p and 18q |
EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). | EXAMPLE: Common (Oligodendroglioma) | EXAMPLE: D, P | ||
| EXAMPLE:
Microsatellite instability - hypermutated |
EXAMPLE: Common (Endometrial carcinoma) | EXAMPLE: P, T | |||
Gene Mutations (SNV/INDEL)
Put your text here and fill in the table (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.)
| 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 |
|---|---|---|---|---|---|---|
| EXAMPLE:EGFR
|
EXAMPLE: Exon 18-21 activating mutations | EXAMPLE: Oncogene | EXAMPLE: Common (lung cancer) | EXAMPLE: T | EXAMPLE: Yes (NCCN) | EXAMPLE: 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). |
| EXAMPLE: TP53; Variable LOF mutations
|
EXAMPLE: Variable LOF mutations | EXAMPLE: Tumor Supressor Gene | EXAMPLE: Common (breast cancer) | EXAMPLE: P | EXAMPLE: >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer. | |
| EXAMPLE: BRAF; Activating mutations | EXAMPLE: Activating mutations | EXAMPLE: Oncogene | EXAMPLE: Common (melanoma) | EXAMPLE: T | ||
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
Put your text here
Genes and Main Pathways Involved
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| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| EXAMPLE: BRAF and MAP2K1; Activating mutations | EXAMPLE: MAPK signaling | EXAMPLE: Increased cell growth and proliferation |
| EXAMPLE: CDKN2A; Inactivating mutations | EXAMPLE: Cell cycle regulation | EXAMPLE: Unregulated cell division |
| EXAMPLE: KMT2C and ARID1A; Inactivating mutations | EXAMPLE: Histone modification, chromatin remodeling | EXAMPLE: Abnormal gene expression program |
Genetic Diagnostic Testing Methods
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Familial Forms
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Additional Information
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Links
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References
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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):
*Citation of this Page: “Primary cutaneous gamma/delta T-cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 10/20/2025, https://ccga.io/index.php/HAEM5:Primary_cutaneous_gamma/delta_T-cell_lymphoma.