Subcutaneous Panniculitis-like T-cell Lymphoma Research Articles

Social Determinants of Health and Outcomes in Cutaneous T-Cell Lymphoma in the State of Georgia

BACKGROUND Cutaneous T-cell lymphomas (CTCL) are a complex group of diseases requiring multidisciplinary care with heterogenous outcomes depending on stage at diagnosis and other clinical and pathologic features. The state of Georgia is a diverse region with 33% Black patients, and a mix of rural, urban, and suburban areas. Prior large database studies have lacked the relevant stage and treatment related data to determine the relative roles of disease characteristics and social determinants of health (SDoH) on outcomes in CTCL. MATERIALS & METHODS. We performed statistical analysis on patients in the Georgia Cancer Registry diagnosed from 2000-2022 with a first or only CTCL primary diagnosis. CTCL was defined by an ICD-0-3 histology code of 9700, 9701, 9702, 9708, 9709, or 9718, and a site of skin primary. Clinical variables included demographics, disease characteristics, and SdoH. We mapped stage at diagnosis at 3-levels (localized, regional, and distant), and SdoH derived from census tracts. The primary endpoints were overall survival (OS) and cause-specific survival (CSS). Univariate and multivariable analyses were assessed by Cox proportional hazards models. RESULTS A total of 1438 patients were in our study cohort. In the state of Georgia, the demographic breakdown was as follows: Male 745 (51.8%), female 693 (48.2%); Race: White 852 (60.1%), Black 538 (37.9%), Other 28 (2.0%), closely mirroring the state demographics. The most common CTCL diagnosis was mycosis fungoides 713 (49.6%). Other diagnoses included: Sezary syndrome (n=18;1.3%), Mature T-cell lymphoma, NOS (n=98; 6.8%), Subcutaneous panniculitis-like T-cell lymphoma (n=8; 0.6%), Cutaneous T-cell lymphoma, NOS (n=444; 30.9%), and primary cutaneous CD30+ T-cell lymphoproliferative disorder (n=157; 10.9%). Stage was localized in 845 patients (58.8%), locally advanced in 140 (9.7%), advanced in 150 (10.4%), and missing in 303 (21.1%). Most patients had private or public insurance, 51 (4.7%) had no insurance. Patient factors associated with inferior OS and CSS included advanced age at diagnosis (CSS, HR 1.03 (95% CI1.03-1.04), p <.001) and higher stage (CSS, Locally advanced HR 4.46 (3.05-6.54), p<.001, Distant HR 6.94 (4.93-9.76) p <.001 vs. Localized). Receipt of chemotherapy, radiation therapy, or immunotherapy (p < 0.001) were all associated with inferior OS and CSS. Lower income and % < poverty were associated with inferior OS but not CSS. Several SoDH were associated with inferior OS and CSS . Less insurance coverage was associated with inferior survival (No insurance HR 2.24 (1.24-4.06), p=0.008, and public insurance HR 1.99 (1.46-2.73), p <001 vs. private insurance). Higher Poverty and lower income were also associated with inferior outcomes. Other social determinants including insurance, % with public assistance, management occupations, % unemployed, % owner occupied, and education did not reach statistical significance. On multivariable analysis, age, stage, and receipt of chemotherapy remained significant for CSS and OS, while sex, insurance, and % < poverty level were significant for OS but not CSS. CONCLUSION In the state of Georgia, advanced stage, receipt of chemotherapy, and lack of insurance were the most important factors determining poorer cause-specific survival among patients with CTCL. Many patients had unclassified CTCL types (37.7%) and missing stage (21.1%), signifying a need for improved diagnostic and staging algorithms in this disease.

Subcutaneous panniculitis-like T-cell lymphoma: Morphological, immunophenotypical and clonality assessment in six cats.

Primary cutaneous lymphoma represents 0.2%-3% of all feline lymphomas, with nonepitheliotropic lymphomas being the most common. In humans and dogs, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a primary nonepitheliotropic lymphoma with a T-cell phenotype developing in the subcutis and often mimicking inflammation. The aim of this report is to describe pathological, phenotypical and clonal features of SPTCL in cats. Six cats with SPTCL were included in this study. Skin biopsies were formalin-fixed, routinely processed and stained. Histological and immunohistochemical investigation for anti-CD18, CD204, CD79a, CD20, CD3, FeLVp27and FeLVgp70 and clonality assessment were performed. Four male and two female domestic shorthair cats, mean age 11.2 years, developed SPTCL in the abdominal (three), inguinal (two) and thoracic (one) regions. Variably pleomorphic neoplastic lymphoid cells were present in the panniculus in percentages, expanding the septa (six of six) and extending into fat lobules in one of six cats. Tumours were associated with elevated numbers of neutrophils (five of six), lesser macrophages (six of six) and variable necrosis (six of six). Neoplastic cells expressed CD3+ (six of six), with clonal T-cell receptor rearrangement detected in five of six cats. This is the first description of SPTCL in cats. Lesions can be confused with panniculitis, leading to delay in diagnosis and therapy. Awareness of this neoplastic disease is relevant to avoid misdiagnoses and to gain greater knowledge about the disease in cats.

Subcutaneous panniculitis-like T-cell lymphoma associated with hemophagocytic lymphohistiocytosis: a systematic review of 63 patients reported in the literature.

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.

Orbital panniculitis-like T-cell lymphoma and review of literature

A 27-year-old patient without a pertinent past medical history presented with chronic orbital inflammation and compressive optic neuropathy. Orbital biopsy with adequate histological and immunohistochemical staining was necessary to identify the disease as subcutaneous panniculitis-like T-cell lymphoma, a rare entity which has only been published as presenting in the orbit on four previous occasions. Immunohistochemical staining is necessary to differentiate the disease from a more benign condition, lupus erythematosus panniculitis, and a more malignant condition, primary cutaneous γδ T-cell lymphoma. The former can be managed with immunosuppression, while the latter may require more aggressive chemotherapy.

IRF8 in Conjunction With CD123 and CD20 to Distinguish Lupus Erythematosus Panniculitis From Subcutaneous Panniculitis-like T-Cell Lymphoma.

Distinguishing lupus erythematosus panniculitis (LEP) from subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a diagnostic challenge with important clinical implications. Immunohistochemical expression of interferon regulatory factor 8 (IRF8) has been shown to highlight cells with plasmacytoid dendritic cell differentiation. Considering that the presence of plasmacytoid dendritic cells highlighted by CD123 immunolabeling is a well-described feature that supports LEP over SPTCL, we hypothesized that IRF8 immunohistochemistry can be used as a diagnostic test to improve accuracy in differentiating LEP from SPTCL. In this study, we assessed the expression of IRF8, CD123, and CD20 in 35 cutaneous biopsies from 31 distinct patients, which included 22 cases of LEP and 13 cases of SPTCL. We found that clusters of IRF8-positive cells within the dermis, and away from subcutaneous fat, could discriminate LEP from SPTCL ( P =0.005). Similarly, CD123-positive clusters in any location were observed in LEP but absent in all cases of SPTCL. In addition, we found that dermal CD20-predominant lymphoid aggregates could help discriminate LEP from SPTCL ( P =0.022). As individual assays, IRF8, CD123, and CD20 were highly specific (100%, 100%, and 92%, respectively) though poorly sensitive (45%, 29%, and 50%, respectively). However, a panel combining IRF8, CD123, and CD20, with at least 1 positive marker was more accurate than any individual marker by receiver operating characteristic curve analysis. Our study provides a rationale for potentially including IRF8 as part of an immunohistochemical panel composed of other currently available markers used to differentiate LEP from SPTCL.

Panniculitic primary cutaneous gamma delta T-cell lymphoma with concomitant features of autoimmune disease emphasizing a pathophysiologic continuum of lupus profundus with the panniculitic T cell lymphomas

Certain T-cell lymphomas exhibit unique homing properties of the neoplastic lymphocytes for the subcutaneous fat. There are two primary forms of subcutaneous panniculitic lymphomas of T-cell origin. One falls under the designation of primary cutaneous gamma-delta T-cell lymphomas (PGD-TCL) whereby there is dominant involvement of the fat defininng a panniculitic form of PGD-TCL. The neoplastic cells are of the gamma-delta subset and are either double negative for CD4 and CD8 and/or can express CD8. They often have an aggressive clinical course. The other form of panniculitic T-cell lymphoma falls under the designation of subcutaneous panniculitis-like T-cell lymphoma (SPTCL). It represents a subcutaneous lymphoma derived from CD8+ T cells of the alpha-beta subset and typically has an indolent course. These two forms of panniculitic T-cell lymphoma exhibit overlapping histologic features with lupus profundus (LP), a putative form of panniculitic T-cell dyscrasia. We present three cases of PGD-TCL of the fat in the setting of lupus erythematosus (LE) (two cases) and dermatomyositis (DM) (one case), respectively. There were concurrent features of LE and DM in their lymphoma biopsies in two cases while a prior biopsy in one was interpreted as LP. In this latter case, the LP diagnosis presaged the diagnosis of panniculitic PGD-TCL by three years. One patient diagnosed with panniculitic PGD-TCL had hemophagocytic syndrome after developing a lupus-like complex including certain supportive serologies such as antibodies to double-stranded DNA following initiation of statin therapy. The second patient presented with PGD-TCL and concomitant features of anti-nuclear matrix 2 (NXP2) DM. The third patient presented in 2003 with LP and overlying skin features of acute LE, initially responding to Plaquenil, and then four years later was diagnosed with PGD-TCL heralded by Plaquenil treatment resistance. Two of the patients died of their lymphoma. All biopsies showed a characteristic histopathology of PGD-TCL. In two cases, the PGD-TCL was associated with overlying LE-cutaneous findings; another case had skin changes of lymphocyte-rich DM. In two cases, the MXA stain was strikingly positive, the surrogate type I interferon marker that is typically upregulated in biopsies of LE and DM. There are eight prior reported cases describing SPTCL with concomitant cutaneous changes of LE. In six cases there was an established history of LE, including LP responding initially to Plaquenil, similar to one of our cases. In the context of SPTCL or panniculitic PGD-TCL, panniculitic T-cell lymphomas can be associated with concomitant clinical and histologic features of LE or DM, including an upregulated type I interferon signature. Identifying histologic features associated with either of these prototypic autoimmune conditions should not be considered exclusionary to diagnosing any panniculitic T-cell lymphoma. A clinical, histomorphologic, and pathophysiologic continuum exists with LP, SPTCL and panniculitic PGD-TCL.

Subcutaneous panniculitis-like T-cell lymphoma in two unrelated individuals with BENTA disease

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous non-Hodgkin lymphoma involving CD8+ T cells, the genetic underpinnings of which remain incompletely understood. Here we report two unrelated patients with B cell Expansion with NF-κB and T cell Anergy (BENTA) disease and a novel presentation of SPTCL. Patient 1 presented early in life with recurrent infections and B cell lymphocytosis, linked to a novel gain-of-function (GOF) CARD11 mutation (p.Lys238del). He developed SPTCL-like lesions and membranoproliferative glomerulonephritis by age 2, treated successfully with cyclosporine. Patient 2 presented at 13 months with splenomegaly, lymphadenopathy, and SPTCL with evidence of hemophagocytic lymphohistiocytosis. Genetic analysis revealed two in cis germline GOF CARD11 variants (p.Glu121Asp/p.Gly126Ser). Autologous bone marrow transplant resulted in SPTCL remission despite persistent B cell lymphocytosis. These cases illuminate an unusual pathological manifestation for BENTA disease, suggesting that CARD11 GOF mutations can manifest in cutaneous CD4+and CD8+ T cell malignancies.

Good prognosis of adult hemophagocytic lymphohistiocytosis associated with the germline HAVCR2 mutation

Hemophagocytic lymphohistiocytosis (HLH) in adults may be idiopathic or secondary to various conditions. Recent studies identified germline hepatitis A virus-cellular receptor 2 (HAVCR2) mutations in subcutaneous panniculitis-like T-cell lymphoma (SPTCL) with HLH. The roles of this mutation in HLH, especially in idiopathic group, have never been explored. Of the 65 HLH cases, we detected germline HAVCR2Y82C mutations in nine (13.8%) cases (five SPTCL and four idiopathic HLH). Other causes of HLH were hematologic malignancies excluding SPTCL (32.3%), idiopathic HLH without HAVCR2 mutation (29.2%), infections (15.3%), and autoimmune diseases (9.2%). Germline HAVCR2 mutation was significantly associated with less anemia and better survival. This defines a distinct subgroup of HLH.

Cytophagic Histiocytic Panniculitis with Undetermined Autoimmune Disease: A Rare Case Report

Cytophagic histiocytic panniculitis is a rare disease, associated with either nonmalignant conditions or subcutaneous panniculitis-like T-cell lymphoma (SPTL), and often also associated with hemophagocytic lymphohistiocytosis (HLH). We report the case of a 63-year-old woman who developed a multiple tender, indurated, erythmatous lesions over the abdomen, back, trunk and limbs. Histopathologic findings from skin biopsy specimens revealed significant lobular panniculitis with benign histiocytes showing hemophagocytosis. ANA by IF was positive. Though it is very rare, to confirm diagnosis of CHP by histopathology is very important as CHP and SPLT may span a clinicopathologic spectrum in which there is a natural disease progression from CHP to fatal SPTL.

Clinical characteristics, survival outcomes, and prognostic factors in subcutaneous panniculitis like T-cell lymphoma: National Cancer Database analysis (2004-2018).

e19548 Background: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare lymphoma accounting for less than 1% of mature T-cell lymphomas. Its natural history is not understood due to lack of large studies with long-term followup and an optimal therapeutic approach is not well-defined. Methods: The National Cancer Database was queried for patients aged 18 years and older diagnosed with SPTCL between 2004 and 2018. We excluded patients who lost to follow-up. Kaplan-Meier and multivariate Cox regression were used in the analyses. Results: 353 patients with SPTCL were included. 63% were females, 62% Caucasian, and 26% African American, 50% had early stage (I and II) and 32% had advanced stage (III and IV). 58.4% received chemotherapy, 38.2% did not receive chemotherapy and 3.4% had unknown chemotherapy status. The median age at diagnosis was 49 years (range 18-90). The median overall survival (mOS) for the whole cohort was not reached In early-stage (N = 178), 49.5% had chemotherapy with 39% receiving single-agent chemotherapy and 60% receiving multi-agent chemotherapy. 18.5% received radiation. In advanced-stage (N = 112), 75.9% received chemotherapy with 19% receiving single-agent chemotherapy and 81% receiving multi-agent chemotherapy. 9.8% received radiation There was no significant difference in the mOS between advanced-stage and early-stage (161.5 months vs not reached, P = 0.051) In early stage, there was no significant difference in the OS between chemotherapy and no chemotherapy (mOS was not reached in both groups, P = 0.324). The same trend was seen in the advanced stage (mOS was not reached in both groups, P = 0.851) Compared to Caucasian, African American patients were younger (median age 47 vs 54 years), but there was no significant difference in disease stage, receiving chemotherapy or radiation or other disease related characteristics (IPI score, B-symptoms, and HIV infection). African American patients had better OS (mOS was not reached, P = 0.003). This significant difference was seen in early stage (mOS was not reached, P = 0.003), but not in advanced stage (mOS 162 vs 122 months, P = 0.113) On multivariate analysis, age and Charlson-Deyo score ≥3 were associated with worse OS (HR 1.028 95% CI 1.005-1.052; P = 0.018 and HR 14.711 95% CI 2.316-93.449; P = 0.004, respectively), whereas disease stage and chemotherapy status did not affect the OS (HR 0.938 95% CI 0.545-1.617; P = 0.819, HR 1.271 95% CI 0.175-9.255; P = 0.813, and HR 0.922 95% CI 0.489-1.738; P = 0.802, respectively). Conclusions: Our study indicates that SPTCL is predominantly an indolent lymphoma associated with long-term survival irrespective of stage and chemotherapy. A conservative therapeutic approach appears to be more appropriate than intensive therapeutic approach in most patients. A risk stratification algorithm is needed to determine the therapeutic intensity.

EXCELLENT OUTCOMES OF SUBCUTANEOUS PANNICULITIS‐LIKE T‐CELL LYMPHOMA TREATED WITH CYCLOSPORIN‐BASED REGIMEN, A MULTICENTER RETROSPECTIVE STUDY IN THAILAND

Background: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of cytotoxic T-cell lymphoma, characterized by primary cutaneous tissue involvement mimicking inflammatory panniculitis. Treatment for this disease is still under debated between conventional chemotherapy or immunosuppressive agents like cyclosporin and prednisolone. Material and Methods: A multicenter retrospective study was conducted among adult patients who was diagnosed as subcutaneous panniculitis-like T-cell lymphoma from January 2013 to December 2020, in 15 medical centers in Thailand. The patient demographic data, treatment regimens which divided into conventional chemotherapy or immunosuppressive agents, and treatment outcomes were retrieved from the Thai lymphoma registry database. All of aspects were analyzed and compared between the treatment group. Results: A total of 34 patients were reviewed in this cohort. The median age was 30 years (range;16–64) with female predominance (67.6%). The majority of patients was diagnosed as advanced stage of disease as Ann Arbor stage IV (58.8%). All patients presented with skin and subcutaneous involvement while one-fourth of them had extra-cutaneous lesions including liver (14.7%) and bone marrow (11%). B symptom was observed in 64% and elevated LDH level in 70.6% of the patients which represented the high disease burden. However, almost all of our patients were in good performance status (ECOG 1–2). For treatment options, 41% of the patients received conventional chemotherapy, mostly CHOP, while 38% received cyclosporin containing regimens. The overall response rate (ORR) was 64% in chemotherapy group and 76% in cyclosporin group, which was comparable. Precisely 57% and 76% of the patients in conventional chemotherapy and cyclosporin treatment, respectively, had complete remission. Patients with Ann Arbor stage IV were received conventional chemotherapy as first-line treatment for 69%, on the other hand, 31% received cyclosporin-based treatment, which was in complete remission around 60% on both groups. With median follow up time of 35.2 months, the overall survival and progression free survival were not reached in both groups. Conclusions: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of cytotoxic T-cell lymphoma which predominantly affects young female and usually presents with extranodal lesions especially skin and subcutaneous tissues, bone marrow, and liver. Patients were responded well to cyclosporin-based treatment both limited and advanced stages of the disease. Keywords: chemotherapy, cyclosporin, Subcutaneous panniculitis-like T-cell lymphoma Keyword: Cutaneous non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.

Pediatric Primary Cutaneous Lymphoma in China: A Retrospective Study

Background: The incidence and clinical features of primary cutaneous lymphoma (PCL) tend to differ by age, gender, geographical, and racial variation. All-aged and adult groups of PCL in various regions have been well demonstrated and compared, while the research concentrating on pediatric PCL is rare, especially in Asian countries. Objective: The aim of this study was to investigate the clinical characteristics of PCL in pediatric population at a single center in China. Methods: We conducted a retrospective study of 101 pediatric cases with PCL, diagnosed at the Institute of Dermatology, Chinese Academy of Medical Sciences, from January 2010 to December 2021. Results: Mycosis fungoides (MF), accounting for 41.6% of the total cases, was the most common subtype in pediatric PCL, and the hypopigmented MF accounted for 47.6% of all the MF cases. Lymphomatoid papulosis and chronic active Epstein-Barr virus infection tied for second place with a proportion of 22.8%. Primary cutaneous anaplastic large cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, primary cutaneous peripheral T-cell lymphoma, rare subtypes and primary cutaneous B-cell lymphoma, respectively, accounted for 2.0%, 4.0%, 4.0%, and 3.0%. Most patients had favorable prognosis during the follow-up. Conclusion: The study suggested that MF was the most common subtype in pediatric PCL in China, and most types of pediatric PCL had favorable prognosis.

Modifying NHL-BFM-90 and HLH-2004 Protocols for a Child with SPLTCL and HLH; Prompt Initiation of Dexamethasone and Etoposide

Subcutaneous panniculitis-like T-cell lymphoma (SPLTCL) which is similar to lobular panniculitis is a subtype of skin lymphoma that is characterized by pleomorphic T cells and benign macrophages. The simultaneous presence of hemophagocytic lymphohistiocytosis (HLH) is the most important and adverse prognostic factor in SPLTCL. SPLTCL is a rare disease with no well-established standard treatment. We report a child with SPLTCL and HLH, who were successfully treated with the modified NHL (non-Hodgkin lymphoma)-BFM(Berlin-Frankfurt-Münster)-90 and HLH-2004 protocols. Patient had persistent fever and subcutaneous masses. SPLTCL with HLH was diagnosed by immunohistochemistry, radiology and laboratory results. SPLTCL with HLH has shown high mortality when treated with a combination of intensive anticancer drugs. Thus, we first administered dexamethasone and etoposide. After this, when we used the modified protocol of NHL-BFM-90 and HLH-2004, patient showed complete resolution of the subcutaneous masses and features of HLH, except for persistent hyperferritinemia. We tried etanercept to reduce high serum ferritin with some effects. In children with diagnosis of SPLTCL with HLH, initiation of immediate and appropriate treatment affects prognosis. Thus, prompt initiation of the agents that can simultaneously control underlying disease as well as secondary HLH could have lead to successful results.

Subcutaneous Panniculitis-like T-cell Lymphoma with a HAVCR2 Mutation Diagnosed After 10 Years of Treatment with Glucocorticoids and Cyclosporine as Lupus Panniculitis: A Case Report.

Subcutaneous panniculitis-like T cell lymphoma (SPTCL) is a very rare cutaneous T cell lymphoma that has been reported to be associated with autoimmune disorders but is most commonly associated with systemic lupus erythematosus. We herein report a 26-year-old man thought to have lupus panniculitis (LP) treated for 10 years with corticosteroids and cyclosporine. After several relapses with panniculitis, he was finally diagnosed with SPTCL, which was confirmed to have a HAVCR2 mutation for p.Tyr82Cys. We emphasize that rheumatologists should be aware of the possibility of SPTCL, despite its rare appearance, when making a diagnosis of LP or when encountering clinical manifestations that are not consistent with LP.

Efficacy of ruxolitinib for HAVCR2 mutation-associated hemophagocytic lymphohistiocytosis and panniculitis manifestations in children.

Frequent germline mutations of HAVCR2, recently identified in subcutaneous panniculitis-like T-cell lymphoma (SPTCL), are associated with an increased risk of hemophagocytic lymphohistiocytosis (HLH). However, SPTCL-HLH represents a challenge because of the difficulties in treatment with poor survival. Its malignant nature, specifically harbouring HAVCR2 mutations, has also been questioned. To better understand its pathology and treatment, we analysed the clinical data of six patients diagnosed at our centre. The median age at onset was 10.5 years (range, 0.8-12.4). Five patients presented with skin lesions of subcutaneous nodules/plaques and/or ulceration. All patients developed HLH; notably, one infant only had HLH without skin involvement. Histopathologically, only two patients were diagnosed with SPTCL and three were reported as panniculitis with no sufficient evidence of lymphoma. Genetically, germline homozygous mutation of HAVCR2 (p.Y82C) was identified in all patients, with a median diagnosis time of 4.6 months. All patients initially received corticosteroids, immunosuppressants or chemotherapy, achieving unfavourable responses. Strikingly, they responded well to ruxolitinib targeting inflammatory cytokines, allowing rapid disease resolution and/or long-term maintenance of remission. The excellent efficacy of ruxolitinib highlights this disease as an inflammatory condition instead of neoplastic nature and indicates novel agents targeting key inflammatory pathways as an encouraging approach for this disease entity.

Germline HAVCR2 mutations and their relation to the clinical spectrum of subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis: results from a multicenter study and meta-analysis.

Germline HAVCR2 mutations are frequently detected in subcutaneous panniculitis-like T-cell lymphoma (SPTCL) patients with/without hemophagocytic lymphohistiocytosis (HLH) but factors associated with variable manifestations remain undetermined. To evaluate clinical variations and associated factors in SPTCL and/or HLH with/without HAVCR2 mutations, we performed direct sequencing of HAVCR2 exon 2 using DNA from patients with SPTCL or idiopathic HLH/HLH-like systemic illnesses, defined by HLH alone without secondary causes. The systematic review and individual patient data (IPD) level meta-analysis which included the present and previously published studies reporting HAVCR2 mutations in SPTCL with/without HLH populations was subsequently conducted using random-effects meta-analysis and multivariate logistic regression. Among 34 patients enrolled, 10 of 28 SPTCL patients developed HLH/HLH-like systemic illnesses. Six cases with HAVCR2Y82C mutation manifested with HLH without panniculitis. Male gender (p=0.03) and age.

Subcutaneous panniculitis-like T-cell lymphoma and steroid-induced depression successfully treated with prednisolone and cyclosporine

Subcutaneous panniculitis-like T-cell lymphoma and steroid-induced depression successfully treated with prednisolone and cyclosporine

499 - The Impact of Stem Cell Transplant on Clinical Outcomes of Primary Cutaneous Gamma-Delta T-Cell Lymphoma, Primary Cutaneous CD8+ Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma, and Subcutaneous Panniculitis-like T-Cell Lymphoma: Analysis of Pooled Databases of Rare Cutaneous Extra-Nodal T-Cell Lymphoma Entities

499 - The Impact of Stem Cell Transplant on Clinical Outcomes of Primary Cutaneous Gamma-Delta T-Cell Lymphoma, Primary Cutaneous CD8+ Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma, and Subcutaneous Panniculitis-like T-Cell Lymphoma: Analysis of Pooled Databases of Rare Cutaneous Extra-Nodal T-Cell Lymphoma Entities

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Scan Findings in a Rare Case of Subcutaneous Panniculitis-Like T-Cell Lymphoma

Skin lymphomas are less common and subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a fairly rare subtype of primary cutaneous lymphoma. Skin lymphomas involve subcutaneous adipose tissues with no involvement of lymph nodes. Diagnosis of these cases is generally a challenge to clinicians. These cases present with fever, weight loss, and local discomfort in the region of involvement of subcutaneous tissues and sometime with skin eczema and rashes. Positron emission tomography/computed tomography (PET/CT) scan can guide in determining the extent of involvement being whole-body imaging and can guide the site of biopsy and can help to prevent misdiagnosis. It also helps in correct and early diagnosis and successful treatment. We report a case of a young adult who presented with pyrexia of unknown origin in which PET/CT scan revealed mildly fluorodeoxyglucose-avid diffuse subcutaneous panniculitis involving the whole body, trunk, and extremities. Biopsy was taken from the most appropriate site according to the PET/CT scan report and reported as SPTCL.

Subcutaneous panniculitis-like T-cell lymphoma presenting as an ulcerated plaque: A case report

Subcutaneous panniculitis-like T-cell lymphoma presenting as an ulcerated plaque: A case report