CHOP is insufficient for newly-diagnosed subcutaneous panniculitis-like T-cell lymphoma patients: A retrospective study of 32 patients in China

CHOP is insufficient for newly-diagnosed subcutaneous panniculitis-like T-cell lymphoma patients: A retrospective study of 32 patients in China | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article CHOP is insufficient for newly-diagnosed subcutaneous panniculitis-like T-cell lymphoma patients: A retrospective study of 32 patients in China Chao Chen, Jingjing Yin, Wei Wang, Danqing Zhao, Chong Wei, Congwei Jia, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4550549/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Jul, 2025 Read the published version in BMC Cancer → Version 1 posted 18 You are reading this latest preprint version Abstract Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of cutaneous lymphoma, and the standard of care for SPTCL has not been well-defined. This retrospective study analyzed the efficacy of the CHOP-regimen in newly-diagnosed SPTCL patients in China. The study reviewed 32 SPTCL patients treated at Peking Union Medical College Hospital over the last two decades. The median age of these patients was 27 years. Among them, 56.3% were female. 50% patients had a PIT score ≥ 2, and 28.1% patients had concurrent hemophagocytic lymphohistiocytosis. Histopathology typically showed a lobular panniculitis with individual adipocytes surrounded by atypical lymphocytes, usually with a CD3 + , CD4 − , CD8 + , CD56 − phenotype. 28 patients (87.5%) received CHOP-like regimen as the first-line treatment. The ORR and CR rate of induction therapy were only 42.9% and 35.7%, respectively. The median PFS and OS were 3.2 months and 147.5 months. Factors, concurrent HLH and PIT ≥ 2, were indicators of shorter PFS in univariate analysis. As the largest retrospective SPTCL cohort in Asia, the result showed that CHOP-like regimen was inadequate as a first-line treatment for SPTCL, emphasizing the need for alternative therapeutic strategies. Subcutaneous panniculitis-like T-cell lymphoma CHOP HLH PIT prognosis Figures Figure 1 Figure 2 Introduction Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an exceedingly rare and distinctive subtype of cutaneous lymphoma primarily affecting subcutaneous adipose tissue. SPTCL accounted for only 0.6% of cutaneous lymphomas in the US[ 1 ]. However, the incidence in Asia is higher, representing from 2–11% of cutaneous T-cell lymphomas[ 2 , 3 ]. SPTCL was initially recognized as a provisional entity in the European Organization for Research and Treatment of Cancer (EORTC) classification in 1991 and subsequently in the World Health Organization (WHO) classification of hematopoietic and lymphoid tumors in 2001[ 4 ]. Two different entities, αβ and γδ variants, of SPTCL were separated since 2008 when EORTC study highlighted the different cell origins and better prognosis of αβ subtype. Meanwhile the adverse impact of hemophagocytic lymphohistiocytosis (HLH) on survival were emphasized. Nowadays, SPTCL is defined as a cytotoxic T cell-mediated lymphoma of αβT-cell origin[ 5 ]. Patients with SPTCL usually had an indolent disease course characterized by multiple relapsed cutaneous lesions. Although a minority of patients would experience an aggressive course characterized by early relapse, multi-organ damages and HLH. Due to its rarity, most studies of SPTCL were retrospective analyses and case reports. After searching PUBMED databases in last 20 years, only 8 relative large-scale retrospective studies are outlined. Two largest studies reviewed 75 American cases and 63 European cases of SPTCL[ 6 , 7 ], but the other study only reported 10 to 27 cases in Taiwan, China, France, Spain, Japan, and Korea[ 8 – 13 ]. Standard therapy of SPTCL is yet to be identified and there is no consensus on initial treatment. Current therapeutic strategies vary widely, encompassing poly-chemotherapy, immunosuppressive medication, radiotherapy, and molecular targeted agents, among others. Poly-chemotherapy, particularly regimens containing anthracyclines, remains a prevalent first choice, though its efficacy as a first-line treatment is debated. Michonneau et.al reported that the complete response rate (CR) was only 28.5% in 7 patients who received conventional polychemotherapy[ 8 ]. More data suggested that immunosuppressive medication may induce better response. Despite the available data, the clinicopathological features of Chinese patients with SPTCL have not been thoroughly characterized. This study aims to fill that gap by assessing the clinical and pathological features of 32 Chinese patients diagnosed with SPTCL, summarizing their clinical-pathological profiles, treatment responses, prognostic factors, and survival outcomes, with a focus on the efficacy of treatment modalities in East Asian populations. Patients and Methods Patients The local ethical review boards approved this retrospective cohort study, conducted at Peking Union Medical College Hospital. All patients were informed, and the procedure was performed under the Declaration of Helsinki. A series of 32 sequential patients, newly diagnosed with SPTCL at Peking Union Medical College Hospital between September 1997 and September 2017, were retrospectively incorporated into the study. The diagnoses of SPTCL were reaffirmed by two autonomous pathologists, utilizing the criteria delineated in the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues[ 14 ]. Patient information was meticulously gathered from electronic medical archives, and the patients were under observation until April 2024. Efficacy evaluation Responses to treatment were evaluated at the interim of induction therapy (4 cycles of treatment) and completion of induction therapy, and classified as complete response (CR), partial response (PR), stable disease (SD) or progression disease (PD), based on 2007 Lugano criteria. HLH was defined according to HLH-2004 criteria[ 15 ]. Statistical analysis Overall survival (OS) was calculated from the date of histologically confirmed diagnosis until the patient’s death or last follow up without an event. Progression-free survival (PFS) was calculated from the date of therapy until disease progression or last follow up. Survival curves were estimated using the method of Kaplan-Meier and used for univariate analysis, and statistical comparison between curves was done by log-rank testing. All factors with P values less than 0.10 were included in the multivariate analysis using the Cox proportional hazards model. All reported p-values are two-sided, and values of p < 0.05 were considered significant. Relationships between subgroups were examined by Pearson test or the Fisher exact test, where appropriate. Statistical analyses were performed with SPSS 20.0 software and Graphpad prism 7.0. Results Clinical characteristics The clinical characteristic of the 32 patients were detailed in Table 1 . This SPTCL cohort consisted of 18 females and 14 males with a median age at diagnosis of 27 years (interquartile range, IQR, 18.3 to 37.5 years). Notably, 10 (31.3%) patients were ≤ 20 years old. Table 1 clinical characteristics of SPTCL patients characteristics N (%) Total patients 32 (100%) Gender Male 14 (43.8%) Female 18 (56.3%) Age (year) Median 27 IQR 18.3–37.5 Skin lesions Face 11 (34.4%) Trunk 18 (56.3%) Upper Extremities 10 (31.3%) Lower Extremities 21 (65.6%) Ulcerations 7 (21.9%) B symptom 26 (81.3%) Lab abnormalities Leucopenia 22 (68.8%) Abnormal liver function 20 (62.5%) Elevated ESR 11 (34.4%) Elevated LDH 24 (75.0%) Elevated hsCRP 17 (53.1%) HLH 9 (28.1%) Associated diseases Autoimmune disease 4 (12.5%) EBV-DNA+ 2 (6.3%) Extracutaneous sites muscle 4 (12.5%) lung 4 (12.5%) Bone marrow 3 (9.4%) intestine 3 (9.4%) breast 1 (3.1%) TNM staging I/II 14 (43.8%) III/IV 18 (56.3%) PIT 0–1 16 (50.0%) ≥ 2 16 (50.0%) IPI 0–2 15 (46.9%) ≥ 3 17 (53.1%) In our study, all patients presented with nodular skin lesions or subcutaneous deep lesions, primarily affecting the lower extremities (65.6%), the trunk (56.3%), and less frequently the upper extremities (31.3%) and face (34.4%). Remarkably, 19 patients were misdiagnosed at their initial visit. They were initially misdiagnosed as panniculitis, systemic lupus erythematosus, vasculitis, and auto-inflammatory diseases. The median time from the onset of symptoms to final diagnosis was 5.9 months (IQR, 3.1 to 14.0 months). 4 patients had concurrent autoimmune diseases, all of which were systemic lupus erythematosus. The assessment of the extent of visceral involvement was primarily through PET scans and biopsies. 12 patients had visceral involvement including muscle (12.5%), lung (12.5%), bone marrow (9.4%), intestine (9.4%), and breast (3.1%). An overwhelming majority of patients (81.3%) exhibited B symptoms. The most common laboratory abnormalities were serum lactic dehydrogenase elevated (75.0%), leukopenia (68.8%), transaminase elevated (62.5%), and C-reactive protein elevated (53.1%). Two patients were positive for EBV-DNA in serum samples. 18 cases (56.3%) were classified as stage III/IV according to TNM stage. The PIT score was high or high-intermediate (PIT ≥ 2) in 16 (50.0%) of 32 patients. 53.1% of the patients had an IPI score of 3 or higher. The HLH-2004 criteria [ 10 ] were met by 9 patients[ 15 ], 9 indicating the development of Hemophagocytic lymphohistiocytosis (HLH). The specifics are outlined in Table S1. According to HLH-2004 criteria. Patients with concurrent HLH exhibited severe and extensive clinical manifestations, primarily presenting with fever (100%), liver damage (100%), leukopenia (100%), hepatosplenomegaly (100%), hyper-ferritinemia (100%), coagulopathy (77.8%). Three patients finally died, resulting in a mortality rate of 33.3%. The diagnostic skin biopsy specimens usually showed a lobular panniculitis with individual adipocytes surrounded by atypical lymphocytes. The immunophenotype results are summarized in Table 2 . Neoplastic T-lymphocytes usually showed a CD3 + , CD4 − , CD8 + , CD56 − phenotype with a high expression of cytotoxic proteins and a high proliferation rate. Compared to European, Japanese and Korean studies, our study showed a similar immunophenotype results. Table 2 Immunophenotypical and molecular characteristics This study GELC study[ 9 ] EORTC study[ 6 ] Japanese cases[ 10 ] Korean study[ 11 ] Chinese study[ 13 ] CD3 27/27 (100) 14/14 (100) 59/62 (95) 15/15 (100) 14/14 (100) 11/11 (100) CD4 0/15 (0) 1/15 (6.6) 0/61 (0) 0/14 (0) 1/13 (7.7) 5/9 (55.6) CD8 17/18 (94.4) 15/16 (93.8) 60/63 (95) 16/16 (100) 12/13(92.3) 10/10 (100) CD30 1/5 (20) 0/8 (0) 0/45 (0) ND 0/8 (0) ND CD56 1/18 (5.6) 0/10 (0) 0/61(0) 0/15 (0) 0/14 (0) 9/11 (81.8) TIA1 12/12 (100) ND ND 11/11 (100) 9/9 (100) 10/10 (100) GranB 13/15 (86.7) ND ND 13/13 (100) 3/4 (75) 9/9 (100) Cytotoxic proteins 18/18 (100) 8/8 (100) 63/63 (100) 15/15 (100) ND 10/10 (100) Beta F1 3/4 (75.0) 5/5 (100) 63/63 (100) 8/8 (100) 5/5 (100) ND EBER 0/7 (0) 0/3 (0) 0/38 (0) 1/12 (8.3) 0/8 (0) 0/8 (0) ki67 ≥ 10% 19/19 (100) 10/10 (100) ND ND ND 11/11 (100) Treatment and outcome 17 of 32 cases were misdiagnosed and had been treated with pre-treatment of immunosuppressive therapies to control inflammatory conditions prior to diagnosis. The treatment regimens after diagnosis of SPTCL were outlined in Table 3 as well as patients’ responses to treatment. 28 patients received conventional chemotherapies as initial treatment after SPTCL was diagnosed, and 82.1% (23/28) of them were treated with CHOP or CHOP-like regimen. The median number of regimen cycles were 2.5. 4 patients didn’t receive any chemotherapy. Table 3 Treatment characteristics of all patients Characteristics N (%) Treatment N (% of total patients) CHOP 12 (37.5%) CHOPE 11 (34.4%) GDP-ML 4 (12.5%) FND 1 (3.1%) Surgery 1 (3.1%) No therapy 3 (9.4%) Number of cycles of first-line chemotherapy N (% of patients receive chemotherapy) <4 19 (67.9%) ≥ 4 9 (32.1%) Response to chemotherapy N (% of patients receive chemotherapy) CR 9 (32.1%) PR 2 (7.1%) SD/PD 17 (60.7%) The objective response rate (ORR) of the 28 patients receiving initial induction chemotherapy was 42.9%. The CR rate and PR rate were 35.7% and 7.1%, respectively. Among the 16 patients who did not achieve remission, 12 patients did not show any response to treatment and 4 patients initially achieved remission but experienced disease progression during treatment. The median follow-up duration was 95.1 months (IQR, 42.0-123.5 months). 5 patients died of disease progression or therapy-related side effects. The mortality rate of our cohort was 25.0%. The median PFS and OS of the entire group of patients was 3.2 months (IQR, 1.7-not reached) and 147.5 months (IQR, 42.1-not reached) (Fig. 1 A and 1 B). The 2-year and 5-year estimated PFS were 38.9%, and 29.2%, respectively. The 2-year and 5-year estimated OS were 79.7% and 74.7%, respectively. According to their responses, 28 patients were divided into two groups: responding group (N = 12, 10 CR and 2 PR) and non-responding group (N = 16). There was no significant difference in baseline age and sex between the two groups. When comparing different prognostic factors, HLH ( p = 0.010) and PIT ≥ 2 ( p = 0.023) were found to be significantly different between the two groups (Table 4 ). In responding group, the median PFS and OS were not been reached. In non-responding group, the median PFS and OS were 1.7 months (IQR, 1.2–2.7 months) and 147.5 months (IQR, 4.6-not reached), respectively (Fig. 1 C and 1 D). The responding group exhibited a significantly longer progression-free survival (PFS) compared to the non-responding group. However, there was no discernible difference in overall survival (OS) between the two groups. Table 4 Characteristics of two groups Characteristics responding (N = 12) Non-responding (N = 16) p value Age: 28.6 29.5 0.847 Sex: male 4 8 0.459 B symptoms: yes 8 14 0.194 Spleno/hepatomegaly: yes 6 11 0.257 WBC (×10 9 ) 4.06 4.37 0.854 Ab. Liver function 5 12 0.121 LDH (U/L) 509.2 735.1 0.143 ESR (mm/h) 22.9 17.0 0.429 HLH: yes 0 7 0.010 Autoimmune disease: yes 1 3 0.417 Extracutaneous involved 4 9 0.276 PIT ≥ 2 2 10 0.023 TNM ≥ III 6 10 0.702 Pre-treatment: yes 6 11 0.441 Death 1 6 0.184 Two patients experienced relapse after the completion of initial induction chemotherapy. Among the 16 cases of primary refractory patients and 2 cases of relapsed patients, a total of 14 received salvage chemotherapy. Subsequent salvage treatments included polychemotherapies followed by hematopoietic stem cell transplantation, immunosuppressive drugs such as cyscloporine and novel drugs such as bortezomib or lenalidomide. Prognostic factors 28 patients who received treatment were included to investigate prognostic factors. We conducted the Cox proportional hazards regression analysis to test which prognostic factors could predict the clinical outcome. The results of univariate and multivariate analysis of PFS were summarized in Table 5 . HLH ( p = 0.010, HR 4.129, 95% CI (1.497–11.387)) and PIT ≥ 2(P = 0.037, HR 2.802(1.063–7.385), 95%CI (1.063–7.385)) were found to significantly affect PFS in univariate analysis. In multivariate analysis including HLH and PIT, no significant predictor was found. No significant predictor was found in univariate and multivariate analysis of OS. Table 5 Univariate and multivariate analysis of PFS Variables Univariate analysis Multivariate analysis HR (95% CI) p value HR (95% CI) p value Sex Male 2.162(0.850–5.501) 0.106 Age Years 1.002(0.968–1.036) 0.926 B symptom yes 2.468(0.707–8.613) 0.157 Hepato/splenomegaly yes 1.394(0.536–3.624) 0.495 Pre-treatment yes 1.880(0.655–5.390) 0.240 WBC ×10 9 1.019(0.881–1.179) 0.798 TNM staging ≥III 1.298(0.501–3.364) 0.591 PIT ≥ 2 2.802(1.063–7.385) 0.037 1.648(0.478–5.681) 0.429 LDH U/L 1.000(0.999–1.001) 0.352 Ab. Liver function yes 2.079(0.763–5.659) 0.152 ESR mm/h 0.990(0.964–1.015) 0.425 Extracutaneous involvement yes 1.159(0.459–2.927) 0.755 HLH yes 4.129(1.497–11.387) 0.010 2.959(0.831–10.539) 0.094 Receiving CHOP-like regimen Yes 0.670(0.193–2.328) 0.528 Receiving VP-16 Yes 0.778(0.301–2.010) 0.604 HLH was an indicator of shorter PFS, the median PFS were 1.7 and 32.1 months for patients with and without HLH, respectively ( p = 0.003, Fig. 2 A). But there was no significant difference in OS between two groups ( p = 0.856, Fig. 2 B). PIT ≥ 2 was also found to significantly affect PFS. The median PFS were 1.8 and 42.1 months for patients with and without PIT ≥ 2, respectively ( p = 0.031, Fig. 2 C). But no significant difference was found in OS between two groups ( p = 0.076, Fig. 2 D). Discussion This is a single center, retrospective of 32 patients diagnosed with SPTCL and treated with polychemotherapy, which is the largest Asian cohort analyzing the clinical profiles, phenotypic features, outcome and prognostic factors in this disease. SPTCL is a rare subtype of PTCL which characterized by neoplastic T cell infiltrating subcutaneous tissue. It is estimated to account for 1% or 2.3% of cutaneous lymphoma cases in European countries and Japan[ 16 , 17 ]. Compared to previous studies, our study yielded similar results with Japanese, Korean or European cases in clinical characteristics, such as young age at onset (compared to other cutaneous T-cell lymphomas), relatively predominance of females, high frequency of laboratory abnormalities. However, our study revealed distinct clinical manifestations not previously documented. A large proportion of our patients (81.3%) exhibited B symptoms, indicating a disseminated and aggressive disease course. In contrast to Willemze’s report in 2008, which reported no visceral involvement out of 63 cases with SPTCL[ 18 ], 12 (37.5%) of our cohort presented with extracutaneous involvement. To our knowledge, there have been only 8 cases of SPTCL with extracutaneous involvement reported so far. The affected sites included bone marrow in 5 cases[ 19 – 21 ]; breast in 2 case[ 22 , 23 ]; lung[ 21 ], liver[ 23 ], spleen[ 23 ] and mesenteric fat[ 24 , 25 ] in one case each. And no significant differences were found in terms of PFS and OS between visceral involvement and no-involvement groups. Histopathology typically showed a lobular panniculitis with individual adipocytes surrounded by atypical lymphocytes, usually with a CD3 + , CD4 − , CD8 + , CD56 − phenotype with a high expression of cytotoxic proteins and a high proliferation rate. This finding was consistent with previous study. SPTCL is considered as having a good prognosis, with overall survival around 70%. but the optimal first-line treatment of SPTCL has been hampered by a lack of large-scale data or clinical trials. Although polychemotherapy was most commonly used, but its role was still controversial. Treatment strategies vary across institutions. European studies showed that SPTCLs may benefit equally from chemotherapy and corticosteroids or immunosuppressive drugs[ 26 , 27 ]. However, the relapse was more frequent in non-chemotherapy group than in the chemotherapy group (56% vs 10%)[ 18 ]. And responses to corticosteroids were often short-lived, lasting less than 6 months[ 28 ]. In Lopez-Lerma’s study, oral steriods or plus methotrexate or cyclosporine A achieved 85% CR rate[ 9 ]. East Asian SPTCL cases revealed that most patients were treated with chemotherapy[ 12 , 29 , 30 ], and achieved CR rate varies between 22% and 42%. Ohtsuka reviewed 16 Janpanese SPTCLs in 2017, the CR rates were 38% and 43% in chemotherapy group and immunosuppressive group, meanwhile 4 patients who achieved CR after immunosuppressive treatment relapsed quickly and retreated with polychemotherapy. Lin’s study reported that CHOP-like regimen induced 67% response rate, but with 80% progression rate[ 12 ]. Our findings demonstrated that with initial chemotherapy, the response rate and CR rate was 42.9% and 35.7%, which was similar to other Asian reports. HLH and PIT score were found to significantly associated with response to initial chemotherapy. The most common manifestation of disease progression is new skin lesions during the treatment, and other cytotoxic chemotherapies were usually useless for this portion of patients. As for refractory/relapsed patients, our experience suggests that chemo-free therapies including novel agents are preferred, such as high-dose corticosteroids plus bortezomib or lenalidomide. HLH is the most important prognosis factor of PFS and OS in SPTCLs. Notably, the incidence of our patients with HLH was higher (9 cases, 28.1%) than that of the European study (17%) or Korean studies (14%)[ 10 , 18 , 29 ]. HLH was found to significantly affect SPTCL patients on PFS (P = 0.010), but not on OS. Our study showed that PIT score was also the independent prognostic factor for PFS in univariate analysis. Due to the reason of multiple lines of salvage treatment and limited case numbers, OS was affected by too many factors to have significant predictors. This study also had limitations. Data of this study was based on retrospective and observational studies and as a single center study, our study would have selected bias. Secondly, despite the largest cohort in Asia, the number of included patients was still small. Therefore, additional studies including larger number of patients and with a longer follow-up period are warranted. In the future, clinicians must cooperate with pathologists and oncologists to diagnosis the disease as soon as possible and to avoid a misdiagnosis. As the largest retrospective study in Asian countries, we addressed clinical profiles, phenotypic features, outcome and prognostic factors in SPTCL. The patients exhibited aggressive course with hyper-inflammatory status and extended area of skin lesions. Although most SPTCLs received CHOP-like therapy, the efficiency was unsatisfied. Novel drugs should be considered as an alternative option. In the future, more studies are needed to establish appropriate treatment strategies for SPTCL and to clarify the predictive factors and identify the patients who will benefit from polychemotherapy or chemo-free therapy. Declarations Acknowledgements The authors are grateful to all participants for their cooperation in this research. Funding Vice-chancellor of research and technology, Hamadan University of Medical Sciences (project No. 140106084396). Author’s contributions All authors contributed to the study conception and design. All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Tayebe Roostaei, Seyed Ali Hosseini1, Mousa Motavalli Haghi, Faeze Foroughi-Parvar, Mehrdad Hajilooi and Mohammad Matini. The first draft of the manuscript was written by Mohammad Matini, and Faeze Foroughi-Parvar and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Ethics approval This study was approved by the Research Ethics Committee of Hamedan University of Medical Sciences with the ethical code of IR.UMSHA.REC.1401.467. Conflict of interest: The authors have no competing financial interests or other conflicts of interest to disclose. Sources of funding: Funding: This study was funded by the National High Level Hospital Clinical Research Funding [2022-PUMCH-B-029] and Capital’s Funds for Health Improvement and Research [2024-2-4011]. Data availability: The data that support the findings of this study are available from the corresponding author upon reasonable request. Ethics approval: This study was carried out in accordance with the principles of good clinical practice and the Declaration of Helsinki, and was approved by the Institutional Review Board of Peking Union Medical College Hospital. Informed consent: All patients provided written informed consent prior to enrolment. Permission to reproduce material from other sources: The article didn't reproduce material from other sources. References Bradford PT, et al. Cutaneous lymphoma incidence patterns in the United States: a population-based study of 3884 cases. Blood. 2009;113(21):5064–73. Dobos G et al. 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Subcutaneous panniculitis-like T-cell lymphoma: a clinicopathologic, immunophenotypic, and molecular study of 22 Asian cases according to WHO-EORTC classification. Am J Surg Pathol. 2008;32(10):1495–502. Additional Declarations No competing interests reported. Supplementary Files TableS1.docx Cite Share Download PDF Status: Published Journal Publication published 24 Jul, 2025 Read the published version in BMC Cancer → Version 1 posted Editorial decision: Revision requested 28 May, 2025 Reviews received at journal 30 Mar, 2025 Reviews received at journal 26 Mar, 2025 Reviews received at journal 23 Mar, 2025 Reviewers agreed at journal 20 Mar, 2025 Reviewers agreed at journal 15 Mar, 2025 Reviewers agreed at journal 15 Mar, 2025 Reviewers agreed at journal 14 Mar, 2025 Reviewers agreed at journal 09 Mar, 2025 Reviewers agreed at journal 09 Mar, 2025 Reviewers agreed at journal 08 Mar, 2025 Reviews received at journal 08 Mar, 2025 Reviewers agreed at journal 03 Mar, 2025 Editor invited by journal 19 Jan, 2025 Reviewers invited by journal 17 Jun, 2024 Editor assigned by journal 11 Jun, 2024 Submission checks completed at journal 10 Jun, 2024 First submitted to journal 08 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4550549","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":318908761,"identity":"5c39c0b6-f5ef-4b11-a868-3032441432a1","order_by":0,"name":"Chao Chen","email":"","orcid":"","institution":"Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences \u0026 Peking Union Medical College","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chao","middleName":"","lastName":"Chen","suffix":""},{"id":318908763,"identity":"89188a9d-cc4b-446c-a941-bea5f7fc78fd","order_by":1,"name":"Jingjing Yin","email":"","orcid":"","institution":"Department of Hematology, Beijing Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jingjing","middleName":"","lastName":"Yin","suffix":""},{"id":318908764,"identity":"e0a9a8b1-a5b6-4bd3-beb5-0ae477d72686","order_by":2,"name":"Wei Wang","email":"","orcid":"","institution":"Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences \u0026 Peking Union Medical College","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Wang","suffix":""},{"id":318908765,"identity":"e679c43f-9b64-477c-8dce-51466ab7125d","order_by":3,"name":"Danqing Zhao","email":"","orcid":"","institution":"Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences \u0026 Peking Union Medical College","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Danqing","middleName":"","lastName":"Zhao","suffix":""},{"id":318908766,"identity":"cb1ff38d-a031-4633-ae78-bfd00ece35b9","order_by":4,"name":"Chong Wei","email":"","orcid":"","institution":"Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences \u0026 Peking Union Medical College","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chong","middleName":"","lastName":"Wei","suffix":""},{"id":318908767,"identity":"7bda2d96-dbac-4792-a486-aeb86025bb50","order_by":5,"name":"Congwei Jia","email":"","orcid":"","institution":"Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences \u0026 Peking Union Medical College","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Congwei","middleName":"","lastName":"Jia","suffix":""},{"id":318908768,"identity":"2f857092-0a9e-4408-ac18-cea7458d86e4","order_by":6,"name":"Wei Zhang","email":"","orcid":"","institution":"Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences \u0026 Peking Union Medical College","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Zhang","suffix":""},{"id":318908769,"identity":"3d5f8b27-e4c0-4eee-92c3-2da4e5470c85","order_by":7,"name":"Daobin Zhou","email":"","orcid":"","institution":"Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences \u0026 Peking Union Medical College","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Daobin","middleName":"","lastName":"Zhou","suffix":""},{"id":318908770,"identity":"196d2763-5c09-4926-8572-3669d147a4ba","order_by":8,"name":"Yan Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+0lEQVRIiWNgGAWjYDACCSjNxsx8/MOHChCTh0gtfOxtaYwzzpCiRY7njBozbxsRWuRnNz97+LXNLo9NIoftMe+8O4lr288eYPi5A7cWxjnHzI1l25KL2SRyjxvO3fYscduZvATG3jO4tTBLJJhJS7YxJ7ZJ5CVIvN12OHHbDR4DZsY23FrYJNK/AbXUA7XkGEjwziFCC49Ejpnkx7bDiW08Z8wkeRuI0CIhkVMmzXDueGIbe1uy4Yxjz4y3nckxONiLR4v8jPRtkj/KqhPnNzMffPCh5o7stuNnDB/8xKMFHAS8bHD2ASQSD2D88QdNyygYBaNgFIwCZAAA2RBXkCpbM1wAAAAASUVORK5CYII=","orcid":"","institution":"Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences \u0026 Peking Union Medical College","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2024-06-08 12:23:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4550549/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4550549/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12885-025-14634-7","type":"published","date":"2025-07-24T15:57:50+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":59435558,"identity":"1088c000-b3e4-4990-9a5f-ca33b61d62d5","added_by":"auto","created_at":"2024-07-01 19:11:04","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":674742,"visible":true,"origin":"","legend":"\u003cp\u003ePFS and OS of SPTCL patients receiving conventional chemotherapies. (A) PFS of 28 patients receiving conventional chemotherapies. (B) OS of 28 patients receiving conventional chemotherapies. (C) PFS of patients in responding group and non-responding group. (D) OS of patients in responding group and non-responding group.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4550549/v1/4ea41bd2c0c137a2c9f76b26.png"},{"id":59435557,"identity":"d321120a-b4b4-4322-8a1e-f639610afe40","added_by":"auto","created_at":"2024-07-01 19:11:04","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":509066,"visible":true,"origin":"","legend":"\u003cp\u003ePFS and OS of SPTCL patients with and without HLH and PIT≥2. (A) PFS of patients with and without HLH. (B) OS of patients with and without HLH. (C) PFS of patients with and without PIT≥2 (D) OS of patients with and without PIT≥2.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-4550549/v1/a347ece0dc456b18ba7f0f34.png"},{"id":87756744,"identity":"9ce6b6e9-0f49-416a-bf2b-760d69c9ba0d","added_by":"auto","created_at":"2025-07-28 16:08:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1182588,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4550549/v1/d1559fa1-c05f-4449-8c58-80bdfce956e6.pdf"},{"id":59435555,"identity":"c4768e18-9e9a-4eef-a4c8-d8ff3bc14404","added_by":"auto","created_at":"2024-07-01 19:11:04","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16983,"visible":true,"origin":"","legend":"","description":"","filename":"TableS1.docx","url":"https://assets-eu.researchsquare.com/files/rs-4550549/v1/7f020160bf8d9102f9ed66ae.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"CHOP is insufficient for newly-diagnosed subcutaneous panniculitis-like T-cell lymphoma patients: A retrospective study of 32 patients in China","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSubcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an exceedingly rare and distinctive subtype of cutaneous lymphoma primarily affecting subcutaneous adipose tissue. SPTCL accounted for only 0.6% of cutaneous lymphomas in the US[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, the incidence in Asia is higher, representing from 2–11% of cutaneous T-cell lymphomas[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. SPTCL was initially recognized as a provisional entity in the European Organization for Research and Treatment of Cancer (EORTC) classification in 1991 and subsequently in the World Health Organization (WHO) classification of hematopoietic and lymphoid tumors in 2001[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Two different entities, αβ and γδ variants, of SPTCL were separated since 2008 when EORTC study highlighted the different cell origins and better prognosis of αβ subtype. Meanwhile the adverse impact of hemophagocytic lymphohistiocytosis (HLH) on survival were emphasized. Nowadays, SPTCL is defined as a cytotoxic T cell-mediated lymphoma of αβT-cell origin[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePatients with SPTCL usually had an indolent disease course characterized by multiple relapsed cutaneous lesions. Although a minority of patients would experience an aggressive course characterized by early relapse, multi-organ damages and HLH. Due to its rarity, most studies of SPTCL were retrospective analyses and case reports. After searching PUBMED databases in last 20 years, only 8 relative large-scale retrospective studies are outlined. Two largest studies reviewed 75 American cases and 63 European cases of SPTCL[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], but the other study only reported 10 to 27 cases in Taiwan, China, France, Spain, Japan, and Korea[\u003cspan additionalcitationids=\"CR9 CR10 CR11 CR12\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e–\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStandard therapy of SPTCL is yet to be identified and there is no consensus on initial treatment. Current therapeutic strategies vary widely, encompassing poly-chemotherapy, immunosuppressive medication, radiotherapy, and molecular targeted agents, among others. Poly-chemotherapy, particularly regimens containing anthracyclines, remains a prevalent first choice, though its efficacy as a first-line treatment is debated. Michonneau et.al reported that the complete response rate (CR) was only 28.5% in 7 patients who received conventional polychemotherapy[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. More data suggested that immunosuppressive medication may induce better response.\u003c/p\u003e \u003cp\u003eDespite the available data, the clinicopathological features of Chinese patients with SPTCL have not been thoroughly characterized. This study aims to fill that gap by assessing the clinical and pathological features of 32 Chinese patients diagnosed with SPTCL, summarizing their clinical-pathological profiles, treatment responses, prognostic factors, and survival outcomes, with a focus on the efficacy of treatment modalities in East Asian populations.\u003c/p\u003e "},{"header":"Patients and Methods","content":"\u003cp\u003ePatients\u003c/p\u003e\u003cp\u003e The local ethical review boards approved this retrospective cohort study, conducted at Peking Union Medical College Hospital. All patients were informed, and the procedure was performed under the Declaration of Helsinki. A series of 32 sequential patients, newly diagnosed with SPTCL at Peking Union Medical College Hospital between September 1997 and September 2017, were retrospectively incorporated into the study. The diagnoses of SPTCL were reaffirmed by two autonomous pathologists, utilizing the criteria delineated in the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Patient information was meticulously gathered from electronic medical archives, and the patients were under observation until April 2024.\u003c/p\u003e\u003cp\u003eEfficacy evaluation\u003c/p\u003e\u003cp\u003eResponses to treatment were evaluated at the interim of induction therapy (4 cycles of treatment) and completion of induction therapy, and classified as complete response (CR), partial response (PR), stable disease (SD) or progression disease (PD), based on 2007 Lugano criteria. HLH was defined according to HLH-2004 criteria[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eOverall survival (OS) was calculated from the date of histologically confirmed diagnosis until the patient’s death or last follow up without an event. Progression-free survival (PFS) was calculated from the date of therapy until disease progression or last follow up. Survival curves were estimated using the method of Kaplan-Meier and used for univariate analysis, and statistical comparison between curves was done by log-rank testing. All factors with P values less than 0.10 were included in the multivariate analysis using the Cox proportional hazards model. All reported p-values are two-sided, and values of p \u0026lt; 0.05 were considered significant. Relationships between subgroups were examined by Pearson test or the Fisher exact test, where appropriate. Statistical analyses were performed with SPSS 20.0 software and Graphpad prism 7.0.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eClinical characteristics\u003c/p\u003e \u003cp\u003eThe clinical characteristic of the 32 patients were detailed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. This SPTCL cohort consisted of 18 females and 14 males with a median age at diagnosis of 27 years (interquartile range, IQR, 18.3 to 37.5 years). Notably, 10 (31.3%) patients were \u0026le;\u0026thinsp;20 years old.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eclinical characteristics of SPTCL patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003echaracteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (43.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (56.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIQR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.3\u0026ndash;37.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSkin lesions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFace\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (34.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTrunk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (56.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUpper Extremities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (31.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLower Extremities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (65.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUlcerations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (21.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB symptom\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (81.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLab abnormalities\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeucopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (68.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbnormal liver function\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (62.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated ESR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (34.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated LDH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (75.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated hsCRP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (53.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHLH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (28.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAssociated diseases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAutoimmune disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEBV-DNA+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtracutaneous sites\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emuscle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003elung\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBone marrow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (9.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eintestine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (9.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ebreast\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTNM staging\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI/II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (43.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII/IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (56.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePIT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIPI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (46.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (53.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn our study, all patients presented with nodular skin lesions or subcutaneous deep lesions, primarily affecting the lower extremities (65.6%), the trunk (56.3%), and less frequently the upper extremities (31.3%) and face (34.4%). Remarkably, 19 patients were misdiagnosed at their initial visit. They were initially misdiagnosed as panniculitis, systemic lupus erythematosus, vasculitis, and auto-inflammatory diseases. The median time from the onset of symptoms to final diagnosis was 5.9 months (IQR, 3.1 to 14.0 months). 4 patients had concurrent autoimmune diseases, all of which were systemic lupus erythematosus.\u003c/p\u003e \u003cp\u003eThe assessment of the extent of visceral involvement was primarily through PET scans and biopsies. 12 patients had visceral involvement including muscle (12.5%), lung (12.5%), bone marrow (9.4%), intestine (9.4%), and breast (3.1%). An overwhelming majority of patients (81.3%) exhibited B symptoms. The most common laboratory abnormalities were serum lactic dehydrogenase elevated (75.0%), leukopenia (68.8%), transaminase elevated (62.5%), and C-reactive protein elevated (53.1%). Two patients were positive for EBV-DNA in serum samples. 18 cases (56.3%) were classified as stage III/IV according to TNM stage. The PIT score was high or high-intermediate (PIT\u0026thinsp;\u0026ge;\u0026thinsp;2) in 16 (50.0%) of 32 patients. 53.1% of the patients had an IPI score of 3 or higher.\u003c/p\u003e \u003cp\u003eThe HLH-2004 criteria [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] were met by 9 patients[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], 9 indicating the development of Hemophagocytic lymphohistiocytosis (HLH). The specifics are outlined in Table S1. According to HLH-2004 criteria. Patients with concurrent HLH exhibited severe and extensive clinical manifestations, primarily presenting with fever (100%), liver damage (100%), leukopenia (100%), hepatosplenomegaly (100%), hyper-ferritinemia (100%), coagulopathy (77.8%). Three patients finally died, resulting in a mortality rate of 33.3%.\u003c/p\u003e \u003cp\u003eThe diagnostic skin biopsy specimens usually showed a lobular panniculitis with individual adipocytes surrounded by atypical lymphocytes. The immunophenotype results are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Neoplastic T-lymphocytes usually showed a CD3\u003csup\u003e+\u003c/sup\u003e, CD4\u003csup\u003e\u0026minus;\u003c/sup\u003e, CD8\u003csup\u003e+\u003c/sup\u003e, CD56\u003csup\u003e\u0026minus;\u003c/sup\u003e phenotype with a high expression of cytotoxic proteins and a high proliferation rate. Compared to European, Japanese and Korean studies, our study showed a similar immunophenotype results.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eImmunophenotypical and molecular characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThis study\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGELC study[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEORTC study[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eJapanese cases[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eKorean study[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eChinese study[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27/27 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14/14 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e59/62 (95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15/15 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14/14 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11/11 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/15 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1/15 (6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/61 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0/14 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1/13 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5/9 (55.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17/18 (94.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15/16 (93.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60/63 (95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16/16 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12/13(92.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10/10 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/5 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/8 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/45 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0/8 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/18 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/10 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/61(0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0/15 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0/14 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9/11 (81.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTIA1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12/12 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11/11 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9/9 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10/10 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGranB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13/15 (86.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13/13 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3/4 (75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9/9 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCytotoxic proteins\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18/18 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8/8 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63/63 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15/15 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10/10 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBeta F1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/4 (75.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5/5 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63/63 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8/8 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5/5 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEBER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/7 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/3 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/38 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1/12 (8.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0/8 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0/8 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eki67\u0026thinsp;\u0026ge;\u0026thinsp;10%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19/19 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10/10 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11/11 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTreatment and outcome\u003c/p\u003e \u003cp\u003e17 of 32 cases were misdiagnosed and had been treated with pre-treatment of immunosuppressive therapies to control inflammatory conditions prior to diagnosis. The treatment regimens after diagnosis of SPTCL were outlined in Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e as well as patients\u0026rsquo; responses to treatment. 28 patients received conventional chemotherapies as initial treatment after SPTCL was diagnosed, and 82.1% (23/28) of them were treated with CHOP or CHOP-like regimen. The median number of regimen cycles were 2.5. 4 patients didn\u0026rsquo;t receive any chemotherapy.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTreatment characteristics of all patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (% of total patients)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCHOP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (37.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCHOPE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (34.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGDP-ML\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (9.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of cycles of first-line chemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (% of patients receive chemotherapy)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (67.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (32.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResponse to chemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (% of patients receive chemotherapy)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (32.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSD/PD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (60.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe objective response rate (ORR) of the 28 patients receiving initial induction chemotherapy was 42.9%. The CR rate and PR rate were 35.7% and 7.1%, respectively. Among the 16 patients who did not achieve remission, 12 patients did not show any response to treatment and 4 patients initially achieved remission but experienced disease progression during treatment. The median follow-up duration was 95.1 months (IQR, 42.0-123.5 months). 5 patients died of disease progression or therapy-related side effects. The mortality rate of our cohort was 25.0%. The median PFS and OS of the entire group of patients was 3.2 months (IQR, 1.7-not reached) and 147.5 months (IQR, 42.1-not reached) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA and \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). The 2-year and 5-year estimated PFS were 38.9%, and 29.2%, respectively. The 2-year and 5-year estimated OS were 79.7% and 74.7%, respectively.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAccording to their responses, 28 patients were divided into two groups: responding group (N\u0026thinsp;=\u0026thinsp;12, 10 CR and 2 PR) and non-responding group (N\u0026thinsp;=\u0026thinsp;16). There was no significant difference in baseline age and sex between the two groups. When comparing different prognostic factors, HLH (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.010) and PIT\u0026thinsp;\u0026ge;\u0026thinsp;2 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.023) were found to be significantly different between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). In responding group, the median PFS and OS were not been reached. In non-responding group, the median PFS and OS were 1.7 months (IQR, 1.2\u0026ndash;2.7 months) and 147.5 months (IQR, 4.6-not reached), respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC and \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD). The responding group exhibited a significantly longer progression-free survival (PFS) compared to the non-responding group. However, there was no discernible difference in overall survival (OS) between the two groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of two groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eresponding\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-responding\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge:\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.847\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex: male\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.459\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB symptoms: yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.194\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpleno/hepatomegaly: yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.257\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC (\u0026times;10\u003csup\u003e9\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.854\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAb. Liver function\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.121\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDH (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e509.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e735.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.143\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESR (mm/h)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.429\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHLH: yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAutoimmune disease: yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.417\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtracutaneous involved\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.276\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePIT\u0026thinsp;\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTNM\u0026thinsp;\u0026ge;\u0026thinsp;III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.702\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-treatment: yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.441\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.184\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTwo patients experienced relapse after the completion of initial induction chemotherapy. Among the 16 cases of primary refractory patients and 2 cases of relapsed patients, a total of 14 received salvage chemotherapy. Subsequent salvage treatments included polychemotherapies followed by hematopoietic stem cell transplantation, immunosuppressive drugs such as cyscloporine and novel drugs such as bortezomib or lenalidomide.\u003c/p\u003e \u003cp\u003ePrognostic factors\u003c/p\u003e \u003cp\u003e28 patients who received treatment were included to investigate prognostic factors. We conducted the Cox proportional hazards regression analysis to test which prognostic factors could predict the clinical outcome. The results of univariate and multivariate analysis of PFS were summarized in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. HLH (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.010, HR 4.129, 95% CI (1.497\u0026ndash;11.387)) and PIT\u0026thinsp;\u0026ge;\u0026thinsp;2(P\u0026thinsp;=\u0026thinsp;0.037, HR 2.802(1.063\u0026ndash;7.385), 95%CI (1.063\u0026ndash;7.385)) were found to significantly affect PFS in univariate analysis. In multivariate analysis including HLH and PIT, no significant predictor was found. No significant predictor was found in univariate and multivariate analysis of OS.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate and multivariate analysis of PFS\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eUnivariate analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eMultivariate analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.162(0.850\u0026ndash;5.501)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.106\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYears\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.002(0.968\u0026ndash;1.036)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.926\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB symptom\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.468(0.707\u0026ndash;8.613)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.157\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHepato/splenomegaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.394(0.536\u0026ndash;3.624)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.495\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.880(0.655\u0026ndash;5.390)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.240\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026times;10\u003csup\u003e9\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.019(0.881\u0026ndash;1.179)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.798\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTNM staging\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.298(0.501\u0026ndash;3.364)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.591\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePIT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.802(1.063\u0026ndash;7.385)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.648(0.478\u0026ndash;5.681)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.429\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eU/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.000(0.999\u0026ndash;1.001)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.352\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAb. Liver function\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.079(0.763\u0026ndash;5.659)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.152\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003emm/h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.990(0.964\u0026ndash;1.015)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.425\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtracutaneous involvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.159(0.459\u0026ndash;2.927)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.755\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHLH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.129(1.497\u0026ndash;11.387)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.959(0.831\u0026ndash;10.539)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.094\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReceiving CHOP-like regimen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.670(0.193\u0026ndash;2.328)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.528\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReceiving VP-16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.778(0.301\u0026ndash;2.010)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.604\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eHLH was an indicator of shorter PFS, the median PFS were 1.7 and 32.1 months for patients with and without HLH, respectively (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). But there was no significant difference in OS between two groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.856, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). PIT\u0026thinsp;\u0026ge;\u0026thinsp;2 was also found to significantly affect PFS. The median PFS were 1.8 and 42.1 months for patients with and without PIT\u0026thinsp;\u0026ge;\u0026thinsp;2, respectively (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.031, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC). But no significant difference was found in OS between two groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.076, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis is a single center, retrospective of 32 patients diagnosed with SPTCL and treated with polychemotherapy, which is the largest Asian cohort analyzing the clinical profiles, phenotypic features, outcome and prognostic factors in this disease.\u003c/p\u003e \u003cp\u003eSPTCL is a rare subtype of PTCL which characterized by neoplastic T cell infiltrating subcutaneous tissue. It is estimated to account for 1% or 2.3% of cutaneous lymphoma cases in European countries and Japan[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Compared to previous studies, our study yielded similar results with Japanese, Korean or European cases in clinical characteristics, such as young age at onset (compared to other cutaneous T-cell lymphomas), relatively predominance of females, high frequency of laboratory abnormalities. However, our study revealed distinct clinical manifestations not previously documented. A large proportion of our patients (81.3%) exhibited B symptoms, indicating a disseminated and aggressive disease course. In contrast to Willemze\u0026rsquo;s report in 2008, which reported no visceral involvement out of 63 cases with SPTCL[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], 12 (37.5%) of our cohort presented with extracutaneous involvement. To our knowledge, there have been only 8 cases of SPTCL with extracutaneous involvement reported so far. The affected sites included bone marrow in 5 cases[\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]; breast in 2 case[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]; lung[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], liver[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], spleen[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] and mesenteric fat[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] in one case each. And no significant differences were found in terms of PFS and OS between visceral involvement and no-involvement groups. Histopathology typically showed a lobular panniculitis with individual adipocytes surrounded by atypical lymphocytes, usually with a CD3\u003csup\u003e+\u003c/sup\u003e, CD4\u003csup\u003e\u0026minus;\u003c/sup\u003e, CD8\u003csup\u003e+\u003c/sup\u003e, CD56\u003csup\u003e\u0026minus;\u003c/sup\u003e phenotype with a high expression of cytotoxic proteins and a high proliferation rate. This finding was consistent with previous study.\u003c/p\u003e \u003cp\u003eSPTCL is considered as having a good prognosis, with overall survival around 70%. but the optimal first-line treatment of SPTCL has been hampered by a lack of large-scale data or clinical trials. Although polychemotherapy was most commonly used, but its role was still controversial. Treatment strategies vary across institutions. European studies showed that SPTCLs may benefit equally from chemotherapy and corticosteroids or immunosuppressive drugs[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. However, the relapse was more frequent in non-chemotherapy group than in the chemotherapy group (56% vs 10%)[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. And responses to corticosteroids were often short-lived, lasting less than 6 months[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In Lopez-Lerma\u0026rsquo;s study, oral steriods or plus methotrexate or cyclosporine A achieved 85% CR rate[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEast Asian SPTCL cases revealed that most patients were treated with chemotherapy[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], and achieved CR rate varies between 22% and 42%. Ohtsuka reviewed 16 Janpanese SPTCLs in 2017, the CR rates were 38% and 43% in chemotherapy group and immunosuppressive group, meanwhile 4 patients who achieved CR after immunosuppressive treatment relapsed quickly and retreated with polychemotherapy. Lin\u0026rsquo;s study reported that CHOP-like regimen induced 67% response rate, but with 80% progression rate[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Our findings demonstrated that with initial chemotherapy, the response rate and CR rate was 42.9% and 35.7%, which was similar to other Asian reports. HLH and PIT score were found to significantly associated with response to initial chemotherapy. The most common manifestation of disease progression is new skin lesions during the treatment, and other cytotoxic chemotherapies were usually useless for this portion of patients. As for refractory/relapsed patients, our experience suggests that chemo-free therapies including novel agents are preferred, such as high-dose corticosteroids plus bortezomib or lenalidomide.\u003c/p\u003e \u003cp\u003eHLH is the most important prognosis factor of PFS and OS in SPTCLs. Notably, the incidence of our patients with HLH was higher (9 cases, 28.1%) than that of the European study (17%) or Korean studies (14%)[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. HLH was found to significantly affect SPTCL patients on PFS (P\u0026thinsp;=\u0026thinsp;0.010), but not on OS. Our study showed that PIT score was also the independent prognostic factor for PFS in univariate analysis. Due to the reason of multiple lines of salvage treatment and limited case numbers, OS was affected by too many factors to have significant predictors.\u003c/p\u003e \u003cp\u003eThis study also had limitations. Data of this study was based on retrospective and observational studies and as a single center study, our study would have selected bias. Secondly, despite the largest cohort in Asia, the number of included patients was still small. Therefore, additional studies including larger number of patients and with a longer follow-up period are warranted. In the future, clinicians must cooperate with pathologists and oncologists to diagnosis the disease as soon as possible and to avoid a misdiagnosis.\u003c/p\u003e \u003cp\u003eAs the largest retrospective study in Asian countries, we addressed clinical profiles, phenotypic features, outcome and prognostic factors in SPTCL. The patients exhibited aggressive course with hyper-inflammatory status and extended area of skin lesions. Although most SPTCLs received CHOP-like therapy, the efficiency was unsatisfied. Novel drugs should be considered as an alternative option. In the future, more studies are needed to establish appropriate treatment strategies for SPTCL and to clarify the predictive factors and identify the patients who will benefit from polychemotherapy or chemo-free therapy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003eThe authors are grateful to all participants for their cooperation in this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003eVice-chancellor of research and technology, Hamadan University of Medical Sciences (project No. 140106084396).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo;s contributions\u0026nbsp;\u003c/strong\u003eAll authors contributed to the study conception and design. All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Tayebe Roostaei, Seyed Ali Hosseini1, Mousa Motavalli Haghi, Faeze Foroughi-Parvar, Mehrdad Hajilooi and Mohammad Matini. The first draft of the manuscript was written by Mohammad Matini, and Faeze Foroughi-Parvar and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u0026nbsp;\u003c/strong\u003eThis study was approved by the Research Ethics Committee of Hamedan University of Medical Sciences with the ethical code of IR.UMSHA.REC.1401.467.\u003c/p\u003e\n\u003cp\u003eConflict of interest: The authors have no competing financial interests or other conflicts of interest to disclose.\u003c/p\u003e\n\u003cp\u003eSources of funding: Funding:\u0026nbsp;This study was funded by the National High Level Hospital Clinical Research Funding [2022-PUMCH-B-029] and Capital\u0026rsquo;s Funds for Health Improvement and Research [2024-2-4011].\u003c/p\u003e\n\u003cp\u003eData availability: The data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003eEthics approval: This study was carried out in accordance with the principles of good clinical practice and the Declaration of Helsinki, and was approved by the Institutional Review Board of Peking Union Medical College Hospital.\u003c/p\u003e\n\u003cp\u003eInformed consent: All patients provided written informed consent prior to enrolment.\u003c/p\u003e\n\u003cp\u003ePermission to reproduce material from other sources: The article didn\u0026apos;t reproduce material from other sources.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBradford PT, et al. Cutaneous lymphoma incidence patterns in the United States: a population-based study of 3884 cases. Blood. 2009;113(21):5064\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDobos G et al. Epidemiology of Cutaneous T-Cell Lymphomas: A Systematic Review and Meta-Analysis of 16,953 Patients. Cancers (Basel), 2020. 12(10).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee MW. Characteristics of cutaneous lymphomas in Korea. Clin Exp Dermatol. 2003;28(6):639\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGonzalez CL, et al. T-cell lymphoma involving subcutaneous tissue. A clinicopathologic entity commonly associated with hemophagocytic syndrome. Am J Surg Pathol. 1991;15(1):17\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWillemze R, Meijer CJ. Classification of cutaneous T-cell lymphoma: from Alibert to WHO-EORTC. J Cutan Pathol. 2006;33(Suppl 1):18\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWillemze R, et al. Subcutaneous panniculitis-like T-cell lymphoma: definition, classification, and prognostic factors: an EORTC Cutaneous Lymphoma Group Study of 83 cases. Blood. 2008;111(2):838\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuitart J, et al. Clinical and Pathological Characteristics and Outcomes Among Patients With Subcutaneous Panniculitis-like T-Cell Lymphoma and Related Adipotropic Lymphoproliferative Disorders. JAMA Dermatol. 2022;158(10):1167\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMichonneau D, et al. Subcutaneous Panniculitis-like T-cell Lymphoma: Immunosuppressive Drugs Induce Better Response than Polychemotherapy. Acta Derm Venereol. 2017;97(3):358\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eL\u0026oacute;pez-Lerma I, et al. Subcutaneous panniculitis-like T-cell lymphoma: Clinical features, therapeutic approach, and outcome in a case series of 16 patients. J Am Acad Dermatol. 2018;79(5):892\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOhtsuka M, Miura T, Yamamoto T. Clinical characteristics, differential diagnosis, and treatment outcome of subcutaneous panniculitis-like T-cell lymphoma: a literature review of published Japanese cases. Eur J Dermatol. 2017;27(1):34\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee D-W, et al. Subcutaneous Panniculitis-Like T-cell Lymphoma: A Clinical and Pathologic Study of 14 Korean Patients. Ann Dermatol. 2011;23(3):329\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin TA, et al. Hematopoietic stem cell transplantation for subcutaneous panniculitis-like T-cell lymphoma: single center experience in an Asian population. Int J Hematol. 2019;109(2):187\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJiang M, et al. Report of Eleven Patients of Subcutaneous Panniculitis-Like T-Cell Lymphoma: Clinicopathologic Features, (18)F-FDG PET/CT Findings and Outcome. Front Oncol. 2021;11:650822.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSwerdlow SH, Harris CE. NL, WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. France: IRAC Presss; 2017.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHenter JI, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWillemze R, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005;105(10):3768\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHamada T, Iwatsuki K. Cutaneous lymphoma in Japan: a nationwide study of 1733 patients. J Dermatol. 2014;41(1):3\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWillemze R, et al. Subcutaneous panniculitis-like T-cell lymphoma: definition, classification, and prognostic factors: an EORTC Cutaneous Lymphoma Group Study of 83 cases. Blood. 2008;111(2):838\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGao J, et al. Bone marrow involvement by subcutaneous panniculitis-like T-cell lymphoma: a report of three cases. Mod Pathol. 2014;27(6):800\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrown NA, et al. Subcutaneous panniculitis-like T-cell lymphoma with bone marrow involvement. Am J Clin Pathol. 2015;143(2):265\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaito A, et al. A Case of Refractory Subcutaneous Panniculitis-like T-cell Lymphoma with Bone Marrow and Lung Involvement Treated Successfully with Oral Etoposide. Acta Derm Venereol. 2018;98(6):610\u0026ndash;1.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchramm N, et al. Subcutaneous panniculitis-like T-cell lymphoma with breast involvement: functional and morphological imaging findings. Br J Radiol. 2010;83(989):e90\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIqbal N, Raina V. \u003cem\u003eSuccessful treatment of disseminated subcutaneous panniculitis-like T-cell lymphoma with single agent oral cyclosporine as a first line therapy.\u003c/em\u003e Case Rep Dermatol Med, 2014. 2014: p. 201836.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLester L, et al. Systemic panniculitis-like T-cell lymphoma with involvement of mesenteric fat and subcutis. 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Immunophenotypic and molecular features, clinical outcomes, treatments, and prognostic factors associated with subcutaneous panniculitis-like T-cell lymphoma: a systematic analysis of 156 patients reported in the literature. Cancer. 2004;101(6):1404\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee DW, et al. Subcutaneous panniculitis-like T-cell lymphoma: a clinical and pathologic study of 14 korean patients. Ann Dermatol. 2011;23(3):329\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKong YY, et al. Subcutaneous panniculitis-like T-cell lymphoma: a clinicopathologic, immunophenotypic, and molecular study of 22 Asian cases according to WHO-EORTC classification. Am J Surg Pathol. 2008;32(10):1495\u0026ndash;502.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Subcutaneous panniculitis-like T-cell lymphoma, CHOP, HLH, PIT, prognosis","lastPublishedDoi":"10.21203/rs.3.rs-4550549/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4550549/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eSubcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of cutaneous lymphoma, and the standard of care for SPTCL has not been well-defined. This retrospective study analyzed the efficacy of the CHOP-regimen in newly-diagnosed SPTCL patients in China. The study reviewed 32 SPTCL patients treated at Peking Union Medical College Hospital over the last two decades. The median age of these patients was 27 years. Among them, 56.3% were female. 50% patients had a PIT score\u0026thinsp;\u0026ge;\u0026thinsp;2, and 28.1% patients had concurrent hemophagocytic lymphohistiocytosis. Histopathology typically showed a lobular panniculitis with individual adipocytes surrounded by atypical lymphocytes, usually with a CD3\u003csup\u003e+\u003c/sup\u003e, CD4\u003csup\u003e\u0026minus;\u003c/sup\u003e, CD8\u003csup\u003e+\u003c/sup\u003e, CD56\u003csup\u003e\u0026minus;\u003c/sup\u003e phenotype. 28 patients (87.5%) received CHOP-like regimen as the first-line treatment. The ORR and CR rate of induction therapy were only 42.9% and 35.7%, respectively. The median PFS and OS were 3.2 months and 147.5 months. Factors, concurrent HLH and PIT\u0026thinsp;\u0026ge;\u0026thinsp;2, were indicators of shorter PFS in univariate analysis. As the largest retrospective SPTCL cohort in Asia, the result showed that CHOP-like regimen was inadequate as a first-line treatment for SPTCL, emphasizing the need for alternative therapeutic strategies.\u003c/p\u003e","manuscriptTitle":"CHOP is insufficient for newly-diagnosed subcutaneous panniculitis-like T-cell lymphoma patients: A retrospective study of 32 patients in China","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-01 19:10:59","doi":"10.21203/rs.3.rs-4550549/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-28T10:11:09+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-03-30T23:00:34+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-03-26T09:02:07+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-03-23T16:08:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"93775983154227601109057747541061889659","date":"2025-03-20T04:20:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"163664436700196246468959217563817254194","date":"2025-03-16T03:48:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"274877877642889506293650643471076748069","date":"2025-03-16T02:36:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"293255478607845991894738832350070096418","date":"2025-03-14T05:25:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"12190280266843842940587573904099649754","date":"2025-03-09T19:47:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"195529669892453609481920148917750250785","date":"2025-03-09T16:29:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"188574809222987194822900075484539347686","date":"2025-03-08T16:56:54+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-03-08T16:24:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"103363983370061483562373935292030143717","date":"2025-03-03T12:59:06+00:00","index":"hide","fulltext":""},{"type":"editorInvited","content":"","date":"2025-01-19T15:00:45+00:00","index":"","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-06-17T14:46:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-11T04:43:31+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-11T03:33:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2024-06-08T12:11:29+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e314ac23-a539-4d4d-9555-f1b06762fa97","owner":[],"postedDate":"July 1st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-28T16:02:22+00:00","versionOfRecord":{"articleIdentity":"rs-4550549","link":"https://doi.org/10.1186/s12885-025-14634-7","journal":{"identity":"bmc-cancer","isVorOnly":false,"title":"BMC Cancer"},"publishedOn":"2025-07-24 15:57:50","publishedOnDateReadable":"July 24th, 2025"},"versionCreatedAt":"2024-07-01 19:10:59","video":"","vorDoi":"10.1186/s12885-025-14634-7","vorDoiUrl":"https://doi.org/10.1186/s12885-025-14634-7","workflowStages":[]},"version":"v1","identity":"rs-4550549","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4550549","identity":"rs-4550549","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}