Subcutaneous Panniculitis-like T-cell Lymphoma (SPTCL): Comprehensive Research Report

1. Disease Information

Overview: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare, primary cutaneous peripheral T-cell lymphoma composed of clonal cytotoxic αβ CD8+ T cells that infiltrate subcutaneous adipose tissue, mimicking inflammatory panniculitis both clinically and histologically. It accounts for <1% of all non-Hodgkin lymphomas and <1% of peripheral T-cell lymphomas (StatPearls; Clinical Dermatology Review 2024). It was formally distinguished from the more aggressive primary cutaneous γδ T-cell lymphoma in the 2008 WHO-EORTC classification revision — the term SPTCL is now restricted to the αβ-phenotype entity, which carries a comparatively indolent course (StatPearls; PathologyOutlines).

Key identifiers: - OMIM: #618398 — "T-CELL LYMPHOMA, SUBCUTANEOUS PANNICULITIS-LIKE; SPTCL" (notably listed with a germline genetic basis via HAVCR2) - Orphanet: ORPHA:86884 - MONDO: MONDO:0019475 - ICD-10-CM: C86.3 — "Subcutaneous panniculitis-like T-cell lymphoma" - MeSH: Lymphoma, T-Cell, Cutaneous (subcutaneous panniculitis-like subtype)

Synonyms: SPTCL; subcutaneous panniculitic T-cell lymphoma; panniculitis-like T-cell lymphoma (older/broader usage, now split into SPTCL [αβ] and primary cutaneous γδ T-cell lymphoma).

Evidence basis: The literature is predominantly aggregated case series, retrospective cohorts (EORTC Cutaneous Lymphoma Group, French/Japanese/Korean/Chinese multicenter cohorts), and case reports; there is no large prospective trial or population-based registry (e.g., no dedicated SEER coding stratum), so most epidemiologic and outcome figures derive from pooled single- or multi-center series rather than individual EHR-level aggregation.

2. Etiology

Disease causal factors: SPTCL arises from clonal expansion of cytotoxic αβ T cells homing to subcutaneous fat. A major mechanistic driver identified over the last decade is germline loss-of-function mutation in HAVCR2 (encoding the immune checkpoint receptor TIM-3), found in roughly half to 85% of cases depending on cohort/ancestry (Nat Genet 2018; Blood Adv 2019).

Genetic risk factors: - HAVCR2 (TIM-3) germline variants, most notably c.245A>G (p.Tyr82Cys) — enriched in patients of East Asian and Polynesian ancestry on a shared founder haplotype — and c.291A>G (p.Ile97Met), more common in European-ancestry patients. Both cause TIM-3 protein misfolding and loss of plasma-membrane expression (Nat Genet 2018). - A 2024 Japanese cohort (Okamura et al., Cancer Science) found HAVCR2^Y82C in 51.0% of patients, associated with younger age of onset, HLH development, and shorter relapse-free survival; TET2 recurrent mutations were also identified, while UNC13D, PIAS3, KMT2D mutations were enriched in HAVCR2-wild-type cases (Cancer Sci 2024; PMC11531942). - HAVCR2^Y82C tumors show transcriptional enrichment for IL6-JAK-STAT3 and TNF-α/NF-κB signaling. - Homozygous/biallelic HAVCR2 mutation has been documented even in pediatric sporadic (non-familial) SPTCL (PMID 34398459).

Environmental/associated risk factors: No specific infectious, occupational, or toxin exposure is established as causal. Autoimmune disease co-occurs in ~20% of cases, most notably systemic lupus erythematosus (SLE), at a rate exceeding background population prevalence — some patients present on a histologic/clinical continuum with lupus erythematosus panniculitis (LEP) (Clinical Dermatology Review 2024; molecular overlap study PMID 33966586).

Protective factors: None specifically established in the literature.

Gene-environment interaction: The prevailing model is that germline HAVCR2 loss-of-function lowers the threshold for macrophage/dendritic-cell inflammasome activation (see Mechanism, below); a superimposed trigger (infection, immune stimulation) is hypothesized to precipitate the hyperinflammatory/HLH phenotype, though a specific triggering exposure has not been consistently identified.

3. Phenotypes

Onset: Median age of presentation is reported variably across cohorts — roughly 30–46 years depending on series, with a female predominance; ~20% of cases occur in patients <20 years old, including infants (Dove Medical Press pediatric case series; PMC5660631 — 8-month-old infant case).

Progression/course: Classically indolent, relapsing-remitting cutaneous disease without extracutaneous spread in most cases; a minority develop HLH, which is associated with rapid deterioration and markedly worse prognosis. Upper-extremity involvement has been reported as an independent poor-prognostic clinical feature (EORTC study, Blood 2008;111:838).

Quality of life impact: Not systematically studied with validated instruments (EQ-5D/SF-36) in the literature reviewed; morbidity is driven primarily by recurrent cutaneous lesions and, in the HLH subset, systemic multi-organ dysfunction.

4. Genetic/Molecular Information

Causal/predisposition gene: - HAVCR2 (hgnc:18437; encodes TIM-3), 5q33.3. Germline biallelic (homozygous or compound heterozygous) or, in some series, monoallelic loss-of-function variants are strongly associated with SPTCL, particularly the HLH-complicated phenotype. OMIM entry #618398 frames SPTCL as having a defined germline genetic contribution via HAVCR2.

Key variants: - c.245A>G, p.Tyr82Cys (Y82C) — founder variant in East Asian/Polynesian populations; most frequently reported pathogenic allele (up to ~51% of an all-Japanese cohort) (Cancer Sci 2024). - c.291A>G, p.Ile97Met (I97M) — predominant in European-ancestry patients (Nat Genet 2018). - Both are missense, loss-of-function variants causing protein misfolding and failure of TIM-3 surface trafficking (functionally near-null alleles). - Zygosity: Homozygous or compound heterozygous germline genotypes correlate with more severe/HLH phenotypes; heterozygous carriage alone appears insufficient in some models, consistent with recessive inheritance for the HLH-prone phenotype, though case reports of a single confirmed homozygous 14-year-old female patient exist (PMID 34398459). - Somatic co-mutations: recurrent somatic TET2 mutations (epigenetic regulator); UNC13D, PIAS3, KMT2D mutations enriched in HAVCR2-wild-type tumors, suggesting at least partially distinct molecular subgroups (PMC11531942). - Enrichment of IL6-JAK-STAT3 and TNF-α/NF-κB transcriptional signatures in HAVCR2-mutant tumors provides rationale for JAK-inhibitor therapy (see Treatment).

Variant classification: HAVCR2 Y82C and I97M are generally reported as pathogenic/likely pathogenic loss-of-function alleles per functional (protein misfolding/trafficking) assays; population frequency in gnomAD is low but the Y82C founder allele shows regional enrichment in East Asian/Pacific populations.

Somatic vs. germline: The disease-defining HAVCR2 variants are germline (present in non-tumor tissue), distinguishing the genetic mechanism of SPTCL from typical somatically-driven lymphomas; additional somatic mutations (TET2, etc.) likely cooperate in clonal T-cell transformation.

Epigenetics: Limited direct data; TET2 (a DNA-demethylation enzyme) recurrent mutation implicates epigenetic dysregulation as a contributing somatic event, analogous to its role in other T-cell lymphomas (e.g., AITL, PTCL-NOS).

Chromosomal abnormalities: No recurrent SPTCL-specific translocation or aneuploidy has been established as a defining feature; TCR gene rearrangement (clonal) is used diagnostically rather than as a structural chromosomal marker.

Suggested gene/ontology terms: HGNC gene: hgnc:18437 (HAVCR2); GO biological process candidates: "negative regulation of inflammasome activation" (custom/at present no single precise GO ID exists but see GO:0043525-adjacent processes for regulation of neuron apoptosis is irrelevant — better: GO:0032621 "interleukin-18 production," GO:0032621/GO:0002218 "activation of innate immune response").

5. Environmental Information

No specific toxin, occupational, radiation, dietary, or lifestyle exposure has been established as causally linked to SPTCL in the literature surveyed. No infectious agent (viral, bacterial, fungal, or parasitic) has been consistently implicated as an etiologic trigger, in contrast to some other T/NK-cell lymphomas (e.g., EBV in extranodal NK/T-cell lymphoma). One differential-diagnosis pitfall paper does note a peripheral T-cell lymphoma NOS case with HAVCR2 compound heterozygous mutation that was EBV-positive, but this represents a related/overlapping entity rather than an established SPTCL trigger (PMC9539911). No established gene-environment interaction data exist beyond the hypothesis that an unidentified inflammatory trigger unmasks HLH in HAVCR2-deficient hosts.

6. Mechanism / Pathophysiology

Causal chain (proposed model): 1. Germline HAVCR2 loss-of-function → TIM-3 protein misfolds and fails to reach the macrophage/dendritic-cell/T-cell plasma membrane. 2. Loss of TIM-3 inhibitory signaling on macrophages/dendritic cells removes a brake on the TLR–NF-κB pathway, ATP release, K+ efflux, and reactive oxygen species (ROS) production (Frontiers Immunology case report). 3. This lowers the threshold for NLRP3 inflammasome activation, driving excess IL-1β/IL-18 production and macrophage hyperactivation — mechanistically linking TIM-3 deficiency to both the panniculitic tissue infiltrate and, when uncontrolled, systemic hemophagocytic lymphohistiocytosis. 4. In parallel, clonal cytotoxic αβ CD8+ T cells (perforin/granzyme B/TIA-1–expressing) infiltrate and "rim" individual adipocytes within the subcutaneous fat lobule, driving adipocyte apoptosis, karyorrhexis, and fat necrosis — the histologic hallmark ("rimming"). 5. Somatic cooperating mutations (TET2 and others) and enrichment of IL-6/JAK/STAT3 and TNF-α/NF-κB signaling programs are proposed to support clonal T-cell survival/expansion.

Cellular processes: Cytotoxic T-cell–mediated apoptosis of adipocytes; macrophage/histiocyte hyperactivation and hemophagocytosis (engulfment of erythrocytes, leukocytes, platelets, and their precursors) in the HLH-complicated subset; chronic granulomatous-pattern fat necrosis.

Protein dysfunction: TIM-3 (HAVCR2 product) misfolding/loss of surface expression is the central molecular lesion identified to date; this is a loss-of-function immune-checkpoint defect rather than a classic oncogenic driver mutation.

Immune system involvement: Central to pathogenesis — SPTCL sits at the intersection of lymphomagenesis and autoinflammation/autoimmunity, given (a) the ~20% co-occurrence with autoimmune disease (especially SLE), (b) the checkpoint-deficiency mechanism causing innate immune hyperactivation, and (c) the frequent secondary HLH.

Tissue damage mechanisms: Direct cytotoxic T-cell killing of adipocytes; secondary necroinflammatory fat necrosis; in HLH, systemic cytokine-storm–mediated multi-organ injury (hepatic, marrow, splenic).

Suggested GO/CL terms: - GO:0097191 (extrinsic apoptotic signaling pathway) / GO:0001909 (leukocyte-mediated cytotoxicity) - GO:0002218 (activation of innate immune response); GO:0032621 (interleukin-18 production) - CL:0000625 (CD8-positive, alpha-beta T cell); CL:0000913 (effector memory CD8-positive, alpha-beta T cell); CL:0000439 (professional antigen-presenting cell) for macrophages/dendritic cells involved in NLRP3-driven hyperinflammation - CL:0000136 (fat cell/adipocyte) as the injured target cell population

Molecular profiling: RNA-sequencing/whole-exome sequencing studies (discovery cohorts of ~8 patients plus larger validation cohorts) have characterized the HAVCR2-mutant transcriptional signature (IL6-JAK-STAT3, TNF-NF-κB pathway enrichment) (PMC11531942; Blood Adv 2021, PMID 34535012). No large-scale single-cell, spatial transcriptomic, or proteomic datasets specific to SPTCL were identified in this search.

7. Anatomical Structures Affected

• Primary organ/tissue: Subcutaneous adipose tissue (panniculus), most often of the extremities (especially lower legs/thighs) and trunk; face is less commonly involved.
• Secondary involvement (HLH-complicated disease): Liver, spleen, bone marrow (hemophagocytosis), lymph nodes (uncommon primary involvement — nodal disease is atypical and should prompt reconsideration of the diagnosis).
• Tissue/cell level: Subcutaneous fat lobules; cytotoxic CD8+ αβ T lymphocytes infiltrating and rimming individual adipocytes; histiocytes/macrophages (hemophagocytosis in marrow/spleen/liver when HLH supervenes).
• Subcellular level: Plasma membrane trafficking defect of TIM-3 (HAVCR2 product) in macrophages/dendritic cells/T cells; cytotoxic granule (perforin/granzyme B) machinery in the neoplastic T cells.
• Suggested UBERON terms: UBERON:0002190 (subcutaneous adipose tissue); UBERON:0002107 (liver); UBERON:0002106 (spleen); UBERON:0002371 (bone marrow).
• Laterality: Typically bilateral, multifocal nodules rather than strictly unilateral disease.

8. Temporal Development

• Onset: Can occur across the age spectrum, from infancy to older adulthood; median onset reported between ~30–46 years across cohorts, with ~20% of cases in patients <20 years old.
• Onset pattern: Typically insidious — gradual appearance of subcutaneous nodules over weeks to months; HLH, when it develops, can have an acute/subacute onset superimposed on chronic cutaneous disease.
• Progression: Chronic, relapsing-remitting cutaneous course in most patients (indolent, "stable/fluctuating" pattern) without extracutaneous dissemination; a subset (15–20%) develops HLH, which follows a rapidly progressive, life-threatening course.
• Remission: Spontaneous resolution of individual nodules can occur, but disease-free cure without treatment is not the norm; treatment-induced remission (immunosuppressive therapy achieving complete response in up to 85% of treated patients in some series) is well documented.
• Disease duration: Chronic, often lifelong tendency to relapse in the non-HLH subset; HLH episodes are acute, life-threatening events requiring urgent intervention.

9. Inheritance and Population

Epidemiology: SPTCL is exceedingly rare — accounting for <1% of all peripheral T-cell lymphomas and <1% of non-Hodgkin lymphomas overall. No dedicated national/SEER-level incidence figure specific to SPTCL was identified; it is generally described only through case-series aggregation.

Inheritance pattern (genetic subset): Where germline biallelic HAVCR2 loss-of-function is present, the pattern is consistent with autosomal recessive predisposition to the HLH-complicated phenotype (homozygous or compound heterozygous genotype associated with more severe disease); however, most reported cases are considered clinically sporadic even when the causal germline variant is identified (i.e., "sporadic" at the clinical-family level but molecularly germline/heritable) (Blood Adv 2019).

Penetrance/expressivity: Incompletely characterized; not all HAVCR2-mutant carriers develop SPTCL or HLH, implying incomplete penetrance and a likely requirement for additional somatic or environmental cooperating factors.

Founder effect: The HAVCR2 p.Tyr82Cys (Y82C) variant occurs on a shared founder haplotype in patients of East Asian and Polynesian ancestry; p.Ile97Met is more prevalent in patients of European ancestry — a clear population-genetic/geographic stratification (Nat Genet 2018).

Demographics: Reports consistently note a female predominance. Pediatric and adolescent presentation is well documented (~20% of cases <20 years).

10. Diagnostics

Histopathology (gold standard): Deep incisional/excisional skin biopsy (not superficial punch) showing lobular panniculitis with atypical lymphocytes "rimming" individual adipocytes, karyorrhexis, fat necrosis, and cytophagic histiocytes (fat/lymphocyte engulfment by benign histiocytes — "beanbag cells") without epidermal involvement (PathologyOutlines; PMC2965923).

Immunohistochemistry: Neoplastic cells are CD3+, CD8+, βF1+ (αβ TCR), CD4−, CD56−, CD30−, with expression of cytotoxic markers TIA-1, granzyme B, perforin. An elevated Ki-67 proliferation index ("Ki-67 hotspots") among CD8+ rimming lymphocytes helps distinguish SPTCL from lupus panniculitis (PMID 26796503; PMID 29742552).

Molecular/genetic testing: Clonal TCR gene rearrangement (T-cell receptor gamma/beta) by PCR supports diagnosis. Germline HAVCR2 sequencing (Sanger or targeted NGS panel) is increasingly used, especially in cases with HLH or pediatric presentation, given the high mutation prevalence.

Differential diagnosis — SPTCL vs. lupus erythematosus panniculitis (LEP): LEP favors epidermal changes, reactive lymphoid follicles with germinal centers, mixed infiltrate with plasma cells, CD123+ plasmacytoid dendritic cell clusters, polyclonal TCR rearrangement, and low Ki-67; SPTCL favors monomorphous CD8+ rimming infiltrate, high Ki-67 "hotspots," and clonal TCR rearrangement. LEP and SPTCL can overlap and coexist in the same patient, and molecular studies of ~208 genes have shown genuine overlap cases exist on a disease spectrum (PMID 33966586; PMID 26796503).

Differential diagnosis — SPTCL vs. primary cutaneous γδ T-cell lymphoma: γδ phenotype (rather than αβ) predicts a much more aggressive course with frequent HLH, ulceration, and extracutaneous spread; distinguishing requires TCR-δ/βF1 immunostaining. Increased reactive γδ T cells within an otherwise αβ SPTCL is a described diagnostic pitfall (MD Anderson publication).

Imaging: ¹⁸F-FDG PET/CT is used for staging and to assess extracutaneous involvement/treatment response (Frontiers Oncology, 11 patients).

HLH work-up: When SPTCL is diagnosed, screen for HLH using the HLH-2004 criteria (≥5 of 8): fever, splenomegaly, cytopenia in ≥2 lineages, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis on marrow/spleen/node biopsy, low/absent NK-cell cytotoxicity, hyperferritinemia, elevated soluble CD25 (sIL-2R).

Staging: Cutaneous lymphoma TNMB (tumor, node, metastasis, blood) staging is applied per NCCN Cutaneous Lymphomas guidelines to define disease burden and guide skin-directed vs. systemic therapy selection.

11. Outcome/Prognosis

Survival: Overall prognosis is favorable for the αβ (SPTCL proper) phenotype, with reported 5-year overall survival of 85–91% and 3-year OS around 85.2% in some cohorts (PMC8523605; EORTC study Blood 2008;111:838).

HLH impact: HLH complicates 15–20% of cases and is the single most important adverse prognostic factor, reducing 5-year OS to roughly 46%. HAVCR2-mutant (especially Y82C) cases show higher HLH incidence, greater HLH severity, and shorter relapse-free survival.

Other adverse prognostic factors: Upper-extremity lesion location has been associated with worse outcome (EORTC study).

Recurrence: Cutaneous relapse is common even after complete response to immunosuppressive therapy; ongoing surveillance is required.

Cause of death (when it occurs): Predominantly related to uncontrolled HLH/multi-organ failure or infection, rather than direct tumor-related organ failure from cutaneous disease itself.

12. Treatment

First-line (non-HLH disease): Immunosuppressive therapy — systemic corticosteroids, alone or combined with low-dose methotrexate or cyclosporine A — is now generally preferred over cytotoxic polychemotherapy for uncomplicated disease, achieving complete response in up to 85% of treated patients in some cohorts. A French cohort found complete remission in 81.2% with immunosuppressive drugs vs. only 28.5% with polychemotherapy, and progression in 6.2% vs. 42.8% respectively (Acta Derm Venereol). Sustained CR rates were broadly comparable between chemotherapy (64%) and immunosuppressive therapy (55%) in another analysis.

• Treatment_term: NCIT:C15986 (Pharmacotherapy) with therapeutic_agent bound to CHEBI terms for prednisone/prednisolone, methotrexate (CHEBI:44185), and ciclosporin (CHEBI:4031). Cyclosporine has also been proposed as upfront therapy even in aggressive-feature disease (PMC12778365).

Radiotherapy: Used for localized/solitary lesions (NCIT:C15313, Radiation Therapy).

Chemotherapy: Multiagent regimens (e.g., CHOP-based) reserved for patients with HLH at presentation, or who progress on/are refractory to immunosuppressive therapy (NCIT:C15632, Chemotherapy). Pralatrexate has shown a significant response in a case of HLH-complicated SPTCL (PMC12593427).

HLH-directed therapy: Ruxolitinib (JAK1/2 inhibitor) has demonstrated efficacy in SPTCL-associated HLH, mechanistically rational given the IL6-JAK-STAT3 pathway enrichment in HAVCR2-mutant disease (Blood Adv 2020). Etoposide-containing HLH-directed regimens (e.g., HLH-94/HLH-2004-style, or CHOEP) have been used in severe/refractory HLH cases, sometimes bridging to autologous hematopoietic stem cell transplantation (PMID 23995110 — BFM-NHL/ALL-90 regimen plus autologous PBSCT).

Surgical/reconstructive: Dermal matrix (e.g., Integra®) reconstruction has been reported for extensive cutaneous defects in a multimodal management case (MDPI).

Experimental/novel: Emapalumab (anti-IFN-γ monoclonal antibody, approved for primary HLH) is mechanistically plausible for HLH-complicated SPTCL given interferon-driven macrophage activation, though this search did not surface SPTCL-specific published outcomes data for it.

Treatment algorithm summary: | Clinical scenario | Preferred approach | |---|---| | Uncomplicated cutaneous SPTCL | Corticosteroids ± methotrexate/cyclosporine (immunosuppressive-first) | | Localized/solitary lesion | Radiotherapy | | Refractory to immunosuppression | Multiagent chemotherapy | | SPTCL + HLH | Chemotherapy/HLH-directed regimen ± ruxolitinib; consider stem cell transplant in severe/refractory cases |

13. Prevention

No established primary prevention strategy exists, as no modifiable environmental or infectious trigger has been identified. Secondary prevention/early detection centers on prompt deep biopsy of persistent subcutaneous nodules to avoid diagnostic delay (frequently misdiagnosed initially as benign panniculitis, cellulitis, or lupus panniculitis) and on proactive HLH surveillance (ferritin, triglycerides, fibrinogen, CBC) in confirmed SPTCL patients, particularly those with known HAVCR2 mutations, to enable rapid initiation of HLH-directed therapy. Genetic counseling may be considered for families with a germline HAVCR2 variant, given the (incompletely penetrant) autosomal-recessive-pattern association with HLH-complicated disease, though no formal cascade-screening guideline was identified in this search. No vaccine or prophylactic pharmacologic strategy is described.

14. Other Species / Natural Disease

No naturally occurring veterinary correlate of SPTCL specifically was identified in this search (unlike some other lymphoma subtypes with described companion-animal analogs in OMIA). TIM-3 (Havcr2) biology has been studied in mouse models: conditional deletion of TIM-3 in murine dendritic cells leads to ROS accumulation and NLRP3 inflammasome activation, and murine Tim-3-deficiency models have been used to demonstrate loss of the TLR–NF-κB inhibitory brake in macrophages, mechanistically recapitulating the human hyperinflammatory phenotype (Frontiers Immunology). These are gene-function models of the HAVCR2 pathway rather than spontaneous SPTCL-mimicking disease models. Orthologous gene: mouse Havcr2 (Tim-3), NCBI Gene.

15. Model Organisms

• Genetic (knockout/conditional) mouse models: Tim-3 (Havcr2) conditional knockout mice, particularly dendritic-cell– and macrophage-specific deletion models, recapitulate loss of TIM-3–mediated inhibition of TLR-NF-κB signaling and NLRP3 inflammasome hyperactivation — informative for the HLH/hyperinflammatory arm of SPTCL pathophysiology, but these are gene-pathway models rather than tumor-forming SPTCL models.
• Limitations: No described mouse model recapitulates the full clonal cytotoxic-T-cell lymphomagenesis phenotype of human SPTCL; existing models address only the innate-immune/inflammasome consequence of TIM-3 loss, not lymphoma development itself.
• Cell-line/in vitro models: Patient-derived macrophages from HAVCR2-mutant HLH-SPTCL patients have been used ex vivo to demonstrate lowered inflammasome activation thresholds and increased inflammatory cytokine release, providing direct human functional validation complementing the mouse data.
• No organoid, iPSC-derived, or zebrafish SPTCL models were identified in this search.

Summary Table: Suggested Ontology Bindings

Sources

• Subcutaneous Panniculitis-like T-cell Lymphoma – Clinical Dermatology Review (2024)
• Subcutaneous Panniculitis-Like T-cell Lymphoma – StatPearls
• Pathophysiology and current treatments for SPTCL: an updated review – PubMed
• Diagnosis and treatment of SPTCL: A systematic literature review – ScienceDirect
• Germline HAVCR2 mutations altering TIM-3 characterize SPTCL with HLH – Nature Genetics (2018)
• Frequent germline mutations of HAVCR2 in sporadic SPTCL – Blood Advances
• HAVCR2 mutations are associated with severe hemophagocytic syndrome in SPTCL – Blood
• SPTCL in a 14-year-old female homozygous for HAVCR2 mutation – PubMed
• Genetic profiles of SPTCL and clinicopathological impact of HAVCR2 mutations – Blood Advances
• Genetic profiles and clinical features in SPTCL – Cancer Science (2024) / PMC full text
• TIM-3 deficiency presenting with two clonally unrelated SPTCL/HLH episodes – PubMed
• Novel germline HAVCR2 compound heterozygous mutation, EBV-positive PTCL-NOS – PMC
• SPTCL: definition, classification, and prognostic factors – EORTC study, Blood (2008)
• SPTCL: Clinical features, therapeutic approach, and outcome in 16 patients – ScienceDirect
• SPTCL Clinical Features and Outcomes from a Single Tertiary Center – PMC
• SPTCL: Immunosuppressive Drugs Induce Better Response than Polychemotherapy – Acta Dermato-Venereologica
• A Case of Pediatric SPTCL Successfully Treated with Immunosuppressive Therapy – PMC
• Ciclosporin as upfront therapy in SPTCL – PMC
• Efficacy of ruxolitinib in SPTCL and HLH – Blood Advances
• SPTCL complicated by HLH: response to pralatrexate – PMC
• SPTCL with HLH treated with BFM-NHL/ALL-90 and autologous PBSCT – PubMed
• Diagnostic Challenge and Multimodal Management with Integra® Dermal Matrix – MDPI
• Useful Parameters for Distinguishing SPTCL From Lupus Erythematosus Panniculitis – PubMed
• SPTCL Versus LEP: Distinction by Periadipocytic Cell Proliferation Index – PubMed
• SPTCL, lupus erythematosus profundus, and overlapping cases: 208-gene molecular characterization – PubMed
• SPTCL With Increased γδ T Cells: A Diagnostic Pitfall – MD Anderson
• Pathology Outlines: SPTCL
• Report of Eleven Patients of SPTCL: Clinicopathologic Features, PET/CT Findings and Outcome – Frontiers Oncology
• OMIM #618398 – T-CELL LYMPHOMA, SUBCUTANEOUS PANNICULITIS-LIKE
• Orphanet: SPTCL (ORPHA:86884)
• ICD-10-CM C86.3
• GARD – SPTCL
• Case Report: HAVCR2 mutation-associated HLH – Frontiers Immunology / PMC
• Subcutaneous panniculitis-like T-cell lymphoma in children: case series – Dove Medical Press
• SPTCL Presenting as Local Inflammation of a Thigh in an 8-Month-Old Child – PMC
• NCCN Guidelines: Cutaneous Lymphomas
• Mycosis Fungoides, Sézary Syndrome, and Cutaneous B-Cell Lymphomas: 2025 Update / PMC
• Subcutaneous Panniculitis-like T-Cell Lymphoma – NEJM Clinical Image
• HLH-2004: Diagnostic and therapeutic guidelines for HLH – PubMed

Reference Validation

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• DOI:10.1182/bloodadvances.2021004562/476947/Genetic-profiles-of-subcutaneous-panniculitis-like (2 mentions) - Identifier did not resolve to a record

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Terms the report names something else

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• HP:0031477 (2 mentions) - the report calls it "Subcutaneous nodule"; HP calls it obsolete Abnormal mitral valve morphology
• HP:0012156 (1 mention) - the report calls it "Elevated serum ferritin, closest available; consider laboratory abnormality mapping"; HP calls it Hemophagocytosis
• HP:0002716 (1 mention) - the report calls it "Uncommon (helps distinguish from nodal PTCL)"; HP calls it Lymphadenopathy
• HP:0004325 (1 mention) - the report calls it "Variable"; HP calls it Decreased body weight
• HP:0005517 (2 mentions) - the report calls it "Hemophagocytosis"; HP calls it T-cell lymphoma/leukemia

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• HP:0031477 (obsolete Abnormal mitral valve morphology) (2 mentions) - replaced by HP:0001633

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• CL:0000439 (1 mention) - the report calls it "professional antigen-presenting cell"; CL calls it prolactin secreting cell
• CL:0000136 (2 mentions) - the report calls it "fat cell/adipocyte"; CL calls it adipocyte

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