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Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare peripheral T-cell lymphoma characterized by cutaneous lesions and immunologic manifestations. The five-year survival rate of SPTCL has been reported to be over 80%, indicating a favorable prognosis. Recent studies have uncovered recurrent germline variants in HAVCR2, encoding an immunomodulator. In this study, we integrated whole-exome sequencing data from 60 samples collected from 36 SPTCL patients, encompassing six patients of our cohort and 30 patients of publicly available data. We identified 138 somatic mutations in skin tumors of 24 patients and HAVCR2 germline mutations in 23 of 29 patients. HAVCR2 p.Tyr82Cys mutations were identified in four of six Japanese patients. During the clinical courses of four patients, cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone were administered to all patients, but it resulted in incomplete responses in all four patients. However, disease conditions of all patients remained stable with additional treatment, including autologous peripheral blood stem cell transplantation. Over a 7.5-year median follow-up, one patient developed autoimmune-related diseases, while one developed other hematological malignancy, resulting in death. To our knowledge, this is the first report of recurrent HAVCR2 germline mutations in Japanese patients, suggesting the necessity for long-term follow-up.

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Although the vast majority of CTCL subtypes are of the CD4+ T-helper cell differentiation phenotype, there is a spectrum of CD8+ variants that manifest wide-ranging clinical, histologic, and phenotypic features that inform the classification of the disease. CD8, like CD4, and cytotoxic molecules (including TIA and granzyme) are readily detectable via IHC staining of tissue and, when expressed on the phenotypically abnormal T-cell population, can help distinguish specific CTCL subtypes. Nonetheless, given that the histopathologic differential for CD8+ lymphoproliferative disorders and lymphomas may range from very indolent lymphomatoid papulosis (LyP) to aggressive entities like CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (AECTCL), CD8 and/or cytotoxic molecule expression alone is insufficient for diagnosis and is not in itself an indicator of prognosis. We present a review of CTCL subtypes that can demonstrate CD8 positivity: CD8+ mycosis fungoides (MF), LyP type D, subcutaneous panniculitis-like T-cell lymphoma (SPTCL), primary cutaneous gamma/delta T-cell lymphoma (PCGDTL), CD8+ AECTCL, and acral CD8+ T-cell lymphoproliferative disorder (acral CD8+ TCLPD). These diseases may have different clinical manifestations and distinctive treatment algorithms. Due to the rare nature of these diseases, it is imperative to integrate clinical, histologic, and immunohistochemical findings to determine an accurate diagnosis and an appropriate treatment plan.

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Hemophagocytic lymphohistiocytosis (HLH) has been described for decades in association with malignancies (M-HLH). While its mechanism is unknown, M-HLH has a poor prognosis, ranging from 10% to 30% overall survival. Mature T-cell lymphomas, diffuse large B-cell lymphoma, and Hodgkin lymphoma, with or without viral co-triggers such as Epstein-Barr virus, are among the most frequent underlying entities. Most M-HLH cases occur at the presentation of malignancy, but they may also occur during therapy as a result of immune compromise from chemotherapy (HLH in the context of immune compromise, IC-HLH) and (typically) disordered response to infection or after immune-activating therapies (Rx-HLH, also known as cytokine release syndrome, CRS). IC-HLH typically occurs months after diagnosis in the context of fungal, bacterial, or viral infection, though it may occur without an apparent trigger. Rx-HLH can be associated with checkpoint blockade, chimeric antigen receptor T-cell therapy, or bispecific T-cell engaging therapy. Until recently, M-HLH diagnosis and treatment strategies were extrapolated from familial HLH (F-HLH), though optimized diagnostic and therapeutic treatment strategies are emerging.

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Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of T-cell lymphomas with a characteristic feature of subcutaneous nodules associated with hemophagocytic lymphohistiocytosis (HLH). Treatment options for SPTCL are mainly chemotherapy (CMT) or immunosuppressive agents with selection currently dependent on physician decisions. Outcomes between the 2 treatment remedies have not yet been comprehensively compared. This study aimed to compare complete remission (CR) rates between SPTCL patients receiving cyclosporin (CSA)-based regimen (CSA +/- steroid) and CMT. The 5-year overall survival (OS) and 5-year progression free survival (PFS) were also analyzed. Clinical data from patients with SPTCL were drawn from the Thai Lymphoma Study Group registry who were newly diagnosed between 2007 and 2023. A total of 93 patients were selected with 45 cases having received CSA-based regimen and 48 cases having received CMT. There were more patients with limited stage at skin in the CSA group (63.8% vs. 36.2%, p = 0.003), while more patients with hepato- and/or splenomegaly were found in the CMT group (56.2% vs. 24.5%; p = 0.002). Germline HAVCR2 mutations were detected in 26/33 (78.8%) cases. The CR rate was significantly higher in patients treated with CSA (87% vs. 58.3%; OR = 6.5 [95%CI, 2.7-15.3]; p = 0.002). At a median follow-up of 87.8 months (range 0-185), the 5-year OS (98% vs. 87%, p = 0.19) and PFS (72.4% vs. 69.2%, p = 0.19) showed a trend favoring patients treated with CSA. Based on our study, CSA-based regimens are the preferred first-line treatment remedy for newly diagnosed SPTCL, especially in patients with limited cutaneous involvement.

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BACKGROUND: Due to its rarity, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is often misdiagnosed as benign panniculitis, and there are no standardized treatment guidelines for SPTCL. Aurora kinase A (AURKA) plays a regulatory role in both mitosis and meiosis. Cells treated with an AURKA inhibitor showed severe mitotic delay, which triggered apoptosis. MATERIALS AND METHODS: Ten cases of SPTCL were collected in this study, and immunohistochemistry was performed to detect AURKA expression in the skin tissues of these cases. Control groups were set as follows: 1) 10 cases of inflammatory panniculitis; 2) 9 healthy individuals. Fisher's exact test was used to compare the positive rates of AURKA among various groups. RESULTS: An average onset age of 27.3 years was found in 10 SPTCL cases. Clinically, these patients primarily presented with multiple subcutaneous nodules on the trunk and lower extremities, accompanied by intermittent high fever. One case showed lymph node metastasis, while no other distant organ metastasis being observed in any case. Pathologically, there was an infiltration of a large number of atypical lymphocytes within the fat lobules, characterized as a cytotoxic type. AURKA stanning was positive in 6 out of 10 SPTCL cases, while no positive cases were found in the control groups. CONCLUSION: 1) SPTCL predominantly affects young individuals and can be identified by nodular erythema on the trunk, intermittent high fever, and infiltration of atypical cytotoxic lymphocytes within fat lobules. 2) For early-stage cases without metastasis, monotherapy with glucocorticoids or immunosuppressants such as cyclosporine can be considered. 3) High expression of AURKA in SPTCL tissues suggests that AURKA could be a potential biomarker for disease diagnosis, providing a theoretical basis for further targeted therapy.

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BACKGROUND AND OBJECTIVE: subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma with indolent behavior, mostly present in women and associated with immunological diseases whose pathogenic background is still poorly understood. SPTCL is associated with lupus erythematosus panniculitis (LEP) and histologically misdiagnosed. OBJECTIVES: the aim of our study was to identify mutations affecting the pathogenesis of both SPTCL and LEP. MATERIALS AND METHODS: we studied a total of 10 SPTCL and 10 LEP patients using targeted Next Generation Sequencing and pyrosequencing. Differences in gene expression between molecular subgroups were investigated using NanoString technology. Clinical data were collected, and correlations sought with the molecular data obtained. RESULTS: the mutational profile of SPTCL and LEP is different. We identified fewer pathogenic mutations than previously reported in SPTCL, noting a single HAVCR2-mutated SPTCL case. Interestingly, 40% of our SPTCL cases showed the pathogenic TP53 (p.Pro72Arg) (P72R) variant. Although cases showing HAVCR2 mutations or the TP53 (P72R) variant had more severe symptomatic disease, none developed hemophagocytic syndrome (HPS). Furthermore, TP53 (P72R)-positive cases were characterized by a lower metabolic signaling pathway and higher levels of CD28 expression and Treg signaling genes. In addition, 30% of our cases featured the same mutation (T735C) of the epigenetic modificatory gene DNMT3A. None of the LEP cases showed mutations in any of the studied genes. CONCLUSIONS: the mutational landscape of SPTCL is broader than previously anticipated. We describe, for the first time, the involvement of the TP53 (P72R) pathogenic variant in this subgroup of tumors, consider the possible role of different genetic backgrounds in the development of SPTCL, and conclude that LEP does not follow the same pathogenic pathway as SPTCL.

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Subcutaneous panniculitis-like T-cell lymphoma (SPTLP), a unique variant of primary cutaneous T-cell lymphomas, clinically mimics subcutaneous panniculitis. It is typified by the development of multiple plaques or subcutaneous erythematous nodules, predominantly on the extremities and trunk. Epidemiological findings reveal a greater incidence in females than males, affecting a wide demographic, including pediatric and adult cohorts, with a median onset age of around 30 years. Diagnosis of SPTLP is complex, hinging on skin biopsy analyses and the identification of T-cell lineage-specific immunohistochemical markers. Treatment modalities for SPTLP are varied; while corticosteroids may be beneficial initially for many patients, a substantial number require chemotherapy, especially in cases of poor response or relapse. Generally, SPTLP progresses slowly, yet approximately 20% of cases advance to hemophagocytic lymphohistiocytosis (HLH), often correlating with a negative prognosis. We report a case of a young male patient presenting with prolonged fever, multiple skin lesions accompanied by HLH, a poor clinical course, and eventual death, diagnosed postmortem with SPTLP. In addition, we also present a literature review of the current evidence of some updates related to SPTLP.

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Acquired generalized lipodystrophy (AGL) is an extremely rare disease that is characterized by loss of body fat affecting nearly all parts of the body. It is often associated with autoimmune diseases or panniculitis, whereas in other patients the underlying etiology is unclear. We report a 52-year-old male individual who was diagnosed with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) that spontaneously went into remission. Years later he developed new subcutaneous nodules most concerning for relapse SPTCL or lupus panniculitis, followed by onset of hemophagocytic lymphohistiocytosis (HLH) that was treated with allogeneic stem cell transplantation. Notably, around the same time, he also developed generalized subcutaneous fat loss of both upper and lower extremities, chest, abdomen, and face that persisted after treatment of the HLH. Whole exome sequencing was performed to search for pathogenic variants that are associated with SPTCL, including those in hepatitis A virus cellular receptor 2 (HAVCR2), but did not detect any potential disease-causing variant. Our report brings to the attention a novel subtype of panniculitis-variety of AGL. Whether generalized loss of subcutaneous fat in this patient is due to lymphoma-associated panniculitis or due to development of adipose tissue-directed autoantibodies as a paraneoplastic "autoimmune" manifestation of SPTCL remains unclear.

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Cutaneous T-cell lymphomas (CTCLs) are a group of lymphoid neoplasms with high relapse rates and no curative treatment other than allogeneic stem cell transplantation (allo-SCT). CTCL is significantly influenced by disruption of JAK/STAT signaling. Therefore, Janus kinase (JAK) inhibitors may be promising for CTCL treatment. This study is a systematic review aiming to investigate the role of JAK inhibitors in the treatment of CTCL, including their efficacy and safety. Out of 438 initially searched articles, we present 13 eligible ones. The overall response rate (ORR) in the treatment with JAK inhibitors in clinical trials was 11-35%, although different subtypes of CTCL showed different ORRs. Mycosis fungoides showed an ORR of 14-45%, while subcutaneous-panniculitis-like T-cell lymphoma (SPTCL) displayed an ORR ranging from 75% to 100%. Five cases were reported having a relapse/incident of CTCL after using JAK inhibitors; of these, three cases were de novo CTCLs in patients under treatment with a JAK inhibitor due to refractory arthritis, and two cases were relapsed disease after graft-versus-host disease treatment following allo-SCT. In conclusion, using JAK inhibitors for CTCL treatment seems promising with acceptable side effects, especially in patients with SPTCL. Some biomarkers, like pS6, showed an association with better responses. Caution should be taken when treating patients with an underlying autoimmune disease and prior immunosuppression.

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Key Clinical message: Subcutaneous panniculitis-like T-cell lymphoma, a primary cutaneous lymphoma, which is described as following a slow course, could claim life. The occurrence of facial and breast nodules, the association with hemophagocytic lymphohistiocytosis, and the extent of necrosis and ulceration are signs of its aggressive nature needing early diagnosis and prompt treatment. Abstract: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare skin disease that accounts for <1% of all peripheral T-cell lymphomas. It is described as following a slow and gradual process. However, it can be associated with a variety of clinical symptoms ranging from mild to severe. Hemophagocytic lymphohistiocytosis (HLH), a rare and potentially fatal hematologic factor that complicates SPTCL in 20% of cases, is an important prognostic factor. We report here an aggressive case of disseminated SPTCL with HLH involving a young woman who presented with extensive necrosis and ulceration at diagnosis. The report highlights the aggressive course of the disease, the occurrence of facial and breast nodules, the association with HLH, and the extent of necrosis and ulceration. The report highlights the poor prognosis despite polychemotherapy regimen use.

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Germline HAVCR2 mutation has been reported to be associated with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) leading to Hemophagocytic lymphohistiocytosis (HLH). Several studies have indicated that HAVCR2 mutation can cause HLH even in the absence of lymphoma, though the exact mechanism remains unclear. In this article, we reported five cases of HAVCR2 mutation-associated HLH. Our analysis revealed an elevated level of IL-1RA in the serum of these patients. Furthermore, we investigated the potential mechanisms underlying HLH associated with HAVCR2 mutation based on changes in cytokine levels. Our findings suggest that HAVCR2 mutation may represent a distinct genetic defect underlying HLH, differing from traditional primary HLH.

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To review and summarize the clinical features, treatment strategies, and prognosis of subcutaneous panniculitis-like T-cell lymphoma complicated with hemophagocytic lymphohistiocytosis (SPTCL-HLH). We searched the Web of Science, Embase, Cochrane Library, and PubMed databases. The keywords were subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis or hemophagocytic syndrome. The patients were divided into a mutated group and a wild-type group based on the existence of HAVCR2 gene mutation. A total of 45 reports, including 63 patients with SPTCL-HLH, were included in the systematic review. Twelve patients detected gene mutations, including 11 with the HAVCR2 gene mutation and 1 with the STXBP2 gene mutation. Thirty-one patients were tested for autoantibodies. Compared with the wild-type group, patients in the mutated group were younger (p = 0.017), and the autoantibody-positive rate was higher (p = 0.006). The main treatment target of 17 patients was to control HLH, yielding an ORR of 88.2%. Two cases relapsed, and both were treated with corticosteroid monotherapy. The corticosteroid monotherapy experienced a higher recurrence rate than the corticosteroids plus other immunoregulatory agents therapy (66.7 vs. 0.0%, p = 0.029). Eighteen patients received initial anthracycline-based chemotherapy, and 50.0% reached remission. The ORR of initial chemotherapy aiming at controlling HLH was higher than those of anthracycline-based chemotherapy (p = 0.015). The ORR was higher in patients initially controlled for HLH versus chemotherapy without HLH control first (90.5 vs. 61.5%, p = 0.024). Interestingly, one patient with juvenile idiopathic arthritis developed SPTCL-HLH during tocilizumab therapy, discontinuing tocilizumab led to a remission of the disease spontaneously. Sixteen patients received stem cell transplantation (SCT). Fifteen patients, including 5 with relapsed/refractory SPTCL-HLH, responded well and survived after receiving SCT. One case who received a sibling-identical SCT relapsed. Further analysis revealed a homozygous HAVCR2 mutation with the donor. The 2-year overall survival (OS) was 91.0% ± 4.4%. There was a significant difference in the OS among patients of different age groups, and patients aged 40-60 had the lowest 2-year OS (66.7% ± 19.2%). Patients with HAVCR2 gene mutations are younger and more likely to be misdiagnosed with autoimmune diseases. Initial treatment of corticosteroids plus immunoregulatory agents attaches great significance to avoiding too aggressive therapies. Intensive anthracycline-based chemotherapy such as CHOP or CHOP-like regimens can also induce long-term remission for aggressive disease. SCT is still a reliable strategy currently. In addition, a watch and wait approach is recommended in patients with mild SPTCL-HLH caused by drugs. The occurrence of HLH does not necessarily mean a more rapidly progressive disease and worse prognosis in patients with SPTCL, but older patients with SPTCL-HLH may be associated with a lower survival rate.

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Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is an extremely rare, indolent skin malignancy that can be difficult to distinguish from autoimmune disease-associated panniculitides. Here, we describe a 12-year-old boy who was diagnosed at age 7 years with dermatomyositis with classical manifestations, including poikiloderma, Gottron's sign, and symmetric muscle weakness. Recently, the boy presented multiple subcutaneous nodules and fever. Histopathological examination and immunohistochemical staining revealed coexistence of SPTL. To our knowledge, this is the first case of dermatomyositis accompanied with SPTL. This case alert clinical physicians of the possibility of SPTL should be considered when a patient with dermatomyositis has new lesions presenting as nodules and unknown fever.

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BACKGROUND: Gamma delta T cells gives rise to a rare malignancy called Primary cutaneous Gamma-Delta T cell lymphoma (PCGDTCL). METHODS: From the National Cancer Database (NCDB), 110 (0.015%) patients with PCGDTCL were identified. RESULTS: Males aged >60 years were the commonest cohort. Caucasian race was the most common (Caucasian: 79.09%, African American:16.36%). Most patients were diagnosed at stage 1 (52.33%), followed by stage 4 (30.23%). On analyzing income categories, <$48,000 group had 48.15% stage 4 (13/27) and 40.74% (11/27) stage 1. Overall survival (OS) of the study group at 3 years by Kaplan-Meier (KM) analysis was 46.6%. African American race (37.5%), income of <$48,000 (27.6%) and government insurance (38.8%) had lower survival rates in KM analysis. In the adjusted hazard ratio (HR) analysis, only age <=40 years compared to >60 years (0.165 [0.036, 0.768], P= .0217) reached significance. Although the group that did not receive any chemotherapy or radiation seemed to have a better survival by KM analysis at 74.3% at 3 years, significance was not seen in the adjusted HR estimates and majority of the patients in this group were stage 1. This group may have received topical treatments which may have not been captured in NCDB. Adjusted analysis also revealed chemoradiation to have a lower mortality risk compared to chemotherapy alone (0.229 [0.079, 0.670], P = .0071), suggesting that aggressive strategies may be required for management when needed. CONCLUSION: Socioeconomic disparities significantly impact access to healthcare and are of particular importance in rare lymphomas.

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This is a case of subcutaneous panniculitis-like T-cell lymphoma (SPTCL) was diagnosed by skin biopsy in a patient who presented with fever and erythema nodosum in the umbilicum following mRNA-1273 COVID-19 vaccination. COVID-19 vaccines may cause SPTCL and skin biopsy may help in the diagnosis of erythema nodosum.

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Cutaneous lymphomas and lymphoid proliferations (LPD) in children, adolescents, and young adults (CAYA) are a heterogeneous group of lymphoid neoplasms that present formidable diagnostic challenges to clinicians and pathologists alike. Although rare overall, cutaneous lymphomas/LPD occur in real-world settings and awareness of the differential diagnosis, potential complications, and various therapeutic approaches will help ensure the optimal diagnostic work-up and clinical management. Lymphomas/LPD involving the skin can occur as primary cutaneous disease in a patient that characteristically has lymphoma/LPD confined to the skin, or as secondary involvement in patients with systemic disease. This review will comprehensively summarize both primary cutaneous lymphomas/LPD that occur in the CAYA population as well as those CAYA systemic lymphomas/LPD with propensity for secondary cutaneous involvement. Focus on the most common primary entities occurring in CAYA will include lymphomatoid papulosis, primary cutaneous anaplastic large cell lymphoma, mycosis fungoides, subcutaneous panniculitis-like T-cell lymphoma, and hydroa vacciniforme lymphoproliferative disorder.

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We herein report a case of subcutaneous panniculitis-like T-cell lymphoma (SPTCL) resembling adult-onset Still's disease (AOSD). A 40-year-old woman presented with a fever, erythema, and painful subcutaneous nodules on the trunk. Laboratory data and a bone marrow analysis showed hemophagocytic syndrome. Although AOSD was suspected, based on a histopathological evaluation of the erythema, she was diagnosed with SPTCL. She was refractory to combination chemotherapy but achieved durable remission with cyclosporine monotherapy. Genetic testing revealed a homozygous HAVCR2 c.245A>G variant (rs184868814) that had caused NLRP3 inflammasome activation. SPTCL and AOSD share a pathogenesis in terms of NLRP3 inflammasome activation, so the clinical phenotype of SPTCL reasonably mimics AOSD.

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Subcutaneous panniculitis-like T cell lymphoma (SPTCL) is a rare cutaneous T cell lymphoma, which is indolent in nature but could claim life if not correctly diagnosed and promptly treated. SPTCL is usually presented clinically as painless subcutaneous and erythematous nodules over the trunk or extremities. Active clinical vigilance for these subcutaneous nodules or panniculitis-like lesions is warranted. A biopsy must be performed in order to make a correct diagnosis. Positron emission tomography scan is utilized for disease staging and treatment follow-up. Due to the rarity of this lymphoma, a standard treatment protocol is not established yet. However, most cases of SPTCL could be treated well under immunosuppressive or polychemotherapeutic drugs except in cases with hemophagocytic syndrome. Hematopoietic stem cell transplantation may be used in refractory or relapse cases. In this review, we presented a case of SPTCL with long-term complete remission. Meanwhile, since most clinical evidences and experiences of SPTCL are based mostly on case reports or small case series, and the understanding of the SPTCL pathophysiology is limited, we reviewed and updated the pathophysiology and treatments of SPTCL.

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PURPOSE: Even though subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and lupus erythematosus panniculitis (LEP) are two separate entities, recently they were claimed to represent two ends of a spectrum of T-cell-mediated orbital lymphoproliferative diseases. METHODS: A 78-year-old woman presented with a 1-month history of right-sided periorbital swelling and redness. There was a palpable mass in the medial right lower eyelid with restriction of upward and lateral gaze. MRI revealed a 14 × 7 mm hypointense lesion in the anteromedial orbit. RESULTS: The systemic and ocular findings, orbital biopsy with histopathology and immunochemistry showed overlapping features of LEP and SPTCL. The patient was consulted with rheumatology and hematology, and the physicians arrived at a consensus that the patient existed in the above-mentioned disease spectrum. She was started on systemic immunosuppressive treatment and her clinical findings improved substantially. CONCLUSIONS: This is the first report of a patient, who presented with orbital mass causing vision loss and gaze restriction that had overlapping clinical and histopathologic features of LEP and SPTCL consistent with this novel disease spectrum, in the literature.

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