Pathology, research and practice最新文献

{"title":"FOXP3 is a favourable prognostic indicator in oesophageal adenocarcinoma","authors":"Mark Bates ,&nbsp;Jason McGrath ,&nbsp;Laura Byrne ,&nbsp;Rishabh Vishwakarma ,&nbsp;Kate Dinneen ,&nbsp;Sarah Ní Mhaolcatha ,&nbsp;John Greene ,&nbsp;Paul Nevins Selvadurai ,&nbsp;Noel Donlon ,&nbsp;Anshul Bhardwaj ,&nbsp;Caroline Brophy ,&nbsp;Joanne Lysaght ,&nbsp;John V. Reynolds ,&nbsp;Jacintha O’Sullivan ,&nbsp;Peter D. Caie ,&nbsp;Margaret R. Dunne","doi":"10.1016/j.prp.2025.156216","DOIUrl":"10.1016/j.prp.2025.156216","url":null,"abstract":"<div><h3>Introduction</h3><div>Oesophageal Adenocarcinoma (OAC) is a cancer with poor prognosis although multimodal treatment has greatly improved clinical outcomes for certain patients. However, currently, there is no way to predict which patients will benefit from neoadjuvant regimens. The level of immune cell tumour infiltration has shown prognostic ability in other cancer types. This study aimed to define the immune landscape of OAC tumours and describe interactions with clinicopathological parameters.</div></div><div><h3>Methods</h3><div>Three micron sections from n = 135 treatment-naïve OAC biopsies were stained using multiplex immunofluorescence for immune markers CD8, CD3, FOXP3, HLA-DR, CD68 and CD163. Expression of the immune markers in the tumour and stroma compartments and other pathological markers such as tumour buds (TB), poorly differentiated clusters (PDCs) and the tumour stroma ratio (TSR) were quantified by digital pathology software and the ability of each marker to predict patient clinical outcomes was investigated.</div></div><div><h3>Results</h3><div>On log-rank analysis stromal expression of FOXP3, CD68 and CD163 and tumour expression of FOXP3 and CD163 were all associated with improved OS (Log-rank p = 0.003, p = 0.0009, p = 0.003, p = 0.015, p = 0.039). PDCs were associated with worse OS (p = 0.039). Multivariate analysis identified tumour expression of FOXP3 as an independent favourable prognostic factor for OS (HR = 0.398, 95 % CI: 0.178–0.887, p = 0.024).</div></div><div><h3>Discussion/Conclusion</h3><div>Stromal expression of CD68, CD163 and FOXP3 and tumour expression of FOXP3 and CD163 were associated with improved outcome while the presence of PDCs was associated with worse outcome. FOXP3 was found to be an independent favourable prognostic factor, highlighting the need to better understand the role of FOXP3 in OAC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156216"},"PeriodicalIF":3.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pancreatic panniculitis associated with presumed advanced pancreatic tumor: A case report and literature review","authors":"Dunya Yang ,&nbsp;Shouyue Chen ,&nbsp;Xiaoyu Zhang ,&nbsp;Xiangwu Lin ,&nbsp;Shaoqin Lin ,&nbsp;Qunxiang Chen ,&nbsp;Zongjing Zhang ,&nbsp;Jie Li ,&nbsp;Xi Chen","doi":"10.1016/j.prp.2025.156214","DOIUrl":"10.1016/j.prp.2025.156214","url":null,"abstract":"<div><div>Pancreatic tumor-associated panniculitis is a rare paraneoplastic syndrome, primarily caused by systemic release of pancreatic enzymes (e.g., lipase) from malignancies like acinar cell carcinoma (ACC), leading to necrotizing inflammation in subcutaneous and other adipose tissues. This report details an 87-year-old female presenting with progressive skin lesions (erythematous rash → indurated swelling → ulceration with purulent drainage), lower limb pain, fever, and markedly elevated lipase (3686.2 U/L). Skin biopsy confirmed lobular panniculitis with characteristic \"ghost cells\". Imaging revealed a pancreatic tail mass and liver lesions. Despite sequential anti-infectives, glucocorticoids, Octreotide, Somatostatin, Ulinastatin, and Cimetidine, her condition deteriorated, culminating in death. Literature review confirms that ACC is the predominant pancreatic tumor type causing panniculitis (accounting for 85 %). Diagnosis hinges on recognizing \"ghost cells\" pathologically and significant hyperlipasemia (often &gt;4000 U/L). Crucially, skin manifestations frequently precede abdominal symptoms, leading to misdiagnosis and delayed cancer management. Controlling panniculitis fundamentally requires treating the primary tumor: surgical resection (including metastases) significantly improves survival; platinum-based chemotherapy (e.g., FOLFOX/FOLFIRINOX) is preferred for ACC; and molecular profiling (BRCA/RAF/NTRK) guided targeted therapy is promising. Prognosis is poor; early recognition via clinician vigilance for unexplained panniculitis and pathologist identification of \"ghost cells\", coupled with multidisciplinary collaboration and aggressive tumor-directed therapy, is essential for improving outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156214"},"PeriodicalIF":3.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrin β5-positive cancer-associated fibroblasts promoting lung adenocarcinoma invasion leading to poor prognosis","authors":"Saori Shibata ,&nbsp;Chihiro Inoue ,&nbsp;Yasuhiro Miki ,&nbsp;Hirotsugu Notsuda ,&nbsp;Hiromichi Niikawa ,&nbsp;Yoshinori Okada ,&nbsp;Takashi Suzuki","doi":"10.1016/j.prp.2025.156215","DOIUrl":"10.1016/j.prp.2025.156215","url":null,"abstract":"<div><div>Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment that interact with tumor cells to promote cancer progression, including lung adenocarcinoma (LUAD). Cell adhesion molecules such as integrins play a crucial role in these interactions; however, the clinicopathological significance of integrin expression in LUAD-associated CAFs remains unclear. Hence, we evaluated the expression of integrins α2, α11, β1, and β5, which have been implicated in the progression of other cancer types, in LUAD specimens from 138 patients using immunohistochemistry. Patients with integrin α2-positive CAFs exhibited fewer adverse pathological prognostic factors. Conversely, integrin α11-, β1-, and β5-positive groups demonstrated poor pathological prognostic factors. Notably, the integrin β5-positive group had larger tumor size, higher recurrence rates, and poorer disease-free survival rates. Integrin β5 expression in CAFs was higher than that in normal fibroblasts <em>in vitro</em>. Knockdown of integrin β5 by siRNA transfection suppressed the invasion of co-cultured adenocarcinoma cells. Results from the cytokine antibody array suggest that monocyte chemoattractant protein-1 (MCP-1) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) enhance invasion. Inhibition of the MAPK pathway also suppressed adenocarcinoma cell invasion by reducing soluble factors, including MCP-1 and TIMP-1. These findings demonstrate that integrin β5 in CAFs promotes lung adenocarcinoma invasion, leading to poor prognosis. Therefore, targeting integrin β5 in CAFs may improve LUAD outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156215"},"PeriodicalIF":3.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145027178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP41 regulates glioma malignancy through Notch1 activation: Insights from in vitro and in vivo studies","authors":"Zhifeng Zhang,&nbsp;Siyu Zhu,&nbsp;Ziwei Wang,&nbsp;Hao Tong,&nbsp;Aobo Zhang,&nbsp;Shiyang Zhang,&nbsp;Liqiang Liu","doi":"10.1016/j.prp.2025.156217","DOIUrl":"10.1016/j.prp.2025.156217","url":null,"abstract":"<div><h3>Background</h3><div>Glioma is the most prevalent and lethal primary adult central nervous system tumor, with limited therapeutic advances despite extensive research. The ubiquitin-proteasome system (UPS), particularly ubiquitin-specific proteases (USPs), plays critical roles in tumorigenesis. USP41, a member of the USP family, is implicated in multiple cancer types, but its function in glioma remains poorly understood. This study aimed to investigate the expression, biological functions, and underlying molecular mechanisms of USP41 in glioma cells and tissues, providing insights for targeted therapies.</div></div><div><h3>Methods</h3><div>USP41 expression levels were examined in clinical glioma specimens, normal brain tissues, and cell lines using qPCR and Western blotting. Bioinformatics analysis was conducted using the GEPIA database and KEGG enrichment to identify related signaling pathways. Functional assays, including CCK-8, EdU, colony formation, Transwell migration/invasion, wound healing, flow cytometry, and a xenograft model, were employed to evaluate proliferation, migration, invasion, apoptosis, and tumor growth. The role of Notch1 signaling in USP41-mediated glioma regulation was assessed through pharmacological activation (Jagged-1).</div></div><div><h3>Results</h3><div>USP41 expression was upregulated in glioma tissues and cell lines and associated with poorer survival. USP41 knockdown significantly inhibited glioma cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while promoting apoptosis in vitro. In vivo, USP41 knockdown reduced tumor size and weight. Mechanistic studies suggested that USP41 enhances glioma progression via the Notch1 pathway.</div></div><div><h3>Conclusions</h3><div>USP41 is a key regulator of glioma growth and invasiveness through Notch1 signaling. Targeting USP41 may represent a promising therapeutic strategy for improving glioma outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156217"},"PeriodicalIF":3.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen receptor conversion in bone, liver and lung metastases from breast cancer","authors":"Peter Podany ,&nbsp;Haiying Zhan ,&nbsp;Di Ai ,&nbsp;Uma Krishnamurti ,&nbsp;Yuanxin Liang","doi":"10.1016/j.prp.2025.156222","DOIUrl":"10.1016/j.prp.2025.156222","url":null,"abstract":"<div><div>Breast cancer treatment is dictated by biomarker status which has been documented to convert between primary tumor and metastases, potentially altering patient management. We investigated breast biomarker conversion in metastases to bone, liver, and lung and its correlation with clinicopathologic factors, prognosis and genetic alterations. Within our cohort of bone (n = 35), liver (n = 20), and lung (n = 13) metastases, there was no significant differences in age at initial diagnosis, sex, laterality, tumor type, and tumor grade of primary tumors. Primary tumors that metastasized to bone and liver had higher ER positivity and intensity as well as more PR positivity than those that metastasized to the lung. Fifteen percent (15 %) of our population (10 out of 68 cases) demonstrated ER conversion, most frequently in liver (35 % in liver vs. 5.7 % in bone, 7.7 % in lung; p &lt; 0.01). Of these, 7 cases converted from positive to negative while 3 (all liver metastases) converted from negative to positive. Cases with any ER conversion were found to have a significantly shorter median survival compared to non-converted cases (12 vs. 38 months; p &lt; 0.0001). We also found TP53 mutations in 2 of 3 cases with conversion from negative to positive and PIK3CA mutations in 4 of 6 cases with conversion from positive to negative. Our study demonstrated that the liver is a metastatic site with a higher chance for ER conversion than bone and lung, and ER conversion from negative to positive is likely to be seen in liver metastasis. Moreover, ER conversions, no matter in which direction, are associated with worse prognosis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156222"},"PeriodicalIF":3.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lycorine ameliorates astrocytic apoptosis and inflammation in cerebral ischemia/reperfusion injury via inhibiting mitochondrial dysfunction via SIRT1-mediated SIRT3/PRDX3 activation","authors":"Yiping Ding,&nbsp;Liping Cao,&nbsp;Dawen Li,&nbsp;Huajie Li,&nbsp;Yi Ren,&nbsp;Xuegan Lian","doi":"10.1016/j.prp.2025.156218","DOIUrl":"10.1016/j.prp.2025.156218","url":null,"abstract":"<div><div>Lycorine (LYC) exerts anti-inflammation, antioxidation, and anti-apoptosis effects on many diseases. However, its impact on cerebral ischemia/reperfusion injury (CI/RI) has not been comprehensively examined yet. Using a murine model of middle cerebral artery occlusion/reperfusion (MCAO/R), we found that LYC administration significantly reduced neurological deficits, cerebral infarction, and cerebral edema, and provided long-term benefits in MCAO/R mice. <em>In vitro</em> studies using oxygen-glucose deprivation/reoxygenation (OGD/R)-induced primary astrocytes demonstrated that LYC enhanced cell viability while simultaneously reducing inflammation and apoptosis. Besides, LYC also alleviated OGD/R-induced mitochondrial dysfunction. Further analysis revealed that LYC enhanced SIRT3-mediated deacetylation of peroxiredoxin 3 (PRDX3), which is crucial for mitochondrial protection. SIRT3 inhibition with 3-TYP or shRNA significantly hindered PRDX3 deacetylation and abated the beneficial effects of LYC on OGD/R-induced astrocytes. Intriguingly, LYC increased SIRT1 expression and activity. Furthermore, the promoting effects of LYC on the deacetylation of PRDX3 mediated by SIRT3, as well as its protective capabilities against OGD/R-induced mitochondrial dysfunction, apoptosis, and inflammation in astrocytes, were abrogated by SIRT1 inhibition with EX527. These results indicate that LYC safeguards against CI/RI-induced apoptosis and inflammation in astrocytes by enhancing mitochondrial function via the SIRT1/SIRT3/PRDX3 pathway.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156218"},"PeriodicalIF":3.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RBBP6-induced destabilization of FOXP3 promotes glucose metabolism and malignant progression of HBV-related hepatocellular carcinoma","authors":"Jian Ge ,&nbsp;Yu Fang ,&nbsp;Yuan Wang","doi":"10.1016/j.prp.2025.156219","DOIUrl":"10.1016/j.prp.2025.156219","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma (HCC) associated with hepatitis B virus (HBV) infection remains a leading cause of cancer-related mortality, yet the molecular mechanisms driving its progression are incompletely understood. Forkhead box P3 (FOXP3), a transcription factor involved in immune regulation, has emerged as a potential regulator in multiple cancers. However, its role in HBV-related HCC remains unexplored.</div></div><div><h3>Methods</h3><div>Quantitative reverse transcription PCR (qRT-PCR) and western blotting assays were utilized to assess FOXP3, retinoblastoma-binding protein 6 (RBBP6), and angiogenesis/metastasis-related markers including vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), transforming growth factor β (TGF-β). Functional assays included CCK-8, flow cytometry, colony formation, Transwell, and tube formation assays to evaluate proliferation, apoptosis, migration, invasion, and angiogenesis. Glucose metabolism was analyzed via colorimetric assays. Protein interactions among FOXP3, RBBP6 and regulatory factor X5 (RFX5) were examined using glutathione S-transferase pull-down, co-immunoprecipitation, ubiquitination, chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assays. A xenograft mouse model was used to validate <em>in vivo</em> tumorigenicity of HBV-related HCC cells.</div></div><div><h3>Results</h3><div>FOXP3 expression was downregulated in HBV-positive HCC tissues and cells, contrasting with RBBP6 upregulation. In addition, FOXP3 overexpression suppressed HepG2.2.15 cell proliferation, migration, invasion, glucose uptake, lactate production, and angiogenesis while promoting apoptosis. Moreover, the result showed that RBBP6 destabilized FOXP3 via ubiquitination, and RBBP6 knockdown inhibited tumorigenicity and glucose metabolism by restoring FOXP3 function. RFX5 transcriptionally activated RBBP6 in HBV-positive HCC cells. Further, the study revealed that RBBP6 knockdown inhibited tumor formation in vivo, accompanied by the increased expression of FOXP3 in the transplanted neoplasms resulting from HBV-positive HCC cells.</div></div><div><h3>Conclusion</h3><div>RBBP6 ubiquitinated and destabilized FOXP3 to enhance glycolytic metabolism and malignant progression of HBV-related HCC. Targeting the RBBP6-FOXP3 axis may offer a novel therapeutic strategy for HBV-driven HCC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156219"},"PeriodicalIF":3.2,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145027008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Not all type of lepidic pattern is useful for distinguishing whether metachronous multiple lung adenocarcinomas are separate primary lung cancers","authors":"Liyan Zhang ,&nbsp;Shengnan Zhao ,&nbsp;Xiaofeng Xie ,&nbsp;Weijie Chen ,&nbsp;Wei Wu ,&nbsp;Weijun Cao ,&nbsp;Chunyan Wu ,&nbsp;Huikang Xie","doi":"10.1016/j.prp.2025.156210","DOIUrl":"10.1016/j.prp.2025.156210","url":null,"abstract":"<div><div>Our research aims to ascertain the value of precursor and outgrowth lepidic in aiding the confirmation of multiple lung adenocarcinomas as separate primary lung cancers (SPLC). A total of 151 patients with metachronous multiple invasive adenocarcinomas were included in this study. Driver mutation tests（at least five genes: EGFR, ALK, KRAS, BRAF, and ROS1） were conducted on 302 tumors collected from 151 patients. And the cases were grouped based on the lepidic pattern status in the second tumor of the paired tumors. When comparing the driver mutation results of paired tumors, precursor lepidic group had a higher rate of mutation inconsistency(56.8 %, 54/95) than outgrowth(23.8 %, 5/21) and no-lepidic groups(34.3 %, 12/35)(<em>p</em> = 0.014). The precursor lepidic group demonstrated significantly better relapse-free survival (RFS: <em>p</em> &lt; 0.001) and overall survival (OS: <em>p</em> &lt; 0.001) than the outgrowth and no-lepidic groups. Although multivariate analysis revealed that the presence of precursor lepidic was not an independent risk factor for RFS (<em>p</em> = 0.489) or OS (<em>p</em> = 0.086), upon eliminating the confounding effects of lepidic content and tumor grade, the precursor lepidic group continued to exhibit a favorable prognostic advantage. In addition, patients with inconsistent mutations have a superior prognosis compared with those with identical or no mutations. However, this effect was more pronounced in tumors lacking the precursor lepidic components. Our findings suggest that precursor lepidic aids in diagnosing multiple lung adenocarcinomas as SPLC, while outgrowth lepidic does not. Additional molecular testing may be helpful in cases without precursor lepidic.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156210"},"PeriodicalIF":3.2,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological features of dermal clear cell sarcoma: A series of 13 cases","authors":"Chao Li ,&nbsp;Chuanfang Liu ,&nbsp;Hongjuan Zhang ,&nbsp;Yingmei Wang ,&nbsp;Wanni Xu ,&nbsp;Xinya Yang ,&nbsp;Ligang Chen ,&nbsp;Qingge Jia ,&nbsp;Mingyang Li","doi":"10.1016/j.prp.2025.156213","DOIUrl":"10.1016/j.prp.2025.156213","url":null,"abstract":"<div><h3>Background</h3><div>Dermal clear cell sarcoma (DCCS) is a rare malignant mesenchymal neoplasm. Owing to the overlaps in its morphological and immunophenotypic profiles with a broad spectrum of tumors exhibiting melanocytic differentiation, it is frequently misdiagnosed as other tumor entities in clinical practice. By systematically analyzing the clinicopathological characteristics, immunophenotypic features, and molecular biological properties of DCCS, this study intends to further enhance pathologists' understanding of this disease and provide a valuable reference for its accurate diagnosis.</div></div><div><h3>Methods</h3><div>A retrospective analysis was conducted on the clinicopathological data of 13 patients diagnosed with DCCS at the First Affiliated Hospital of Air Force Medical University from January 2012 to December 2024. The histopathological features, immunophenotypic profiles, and molecular characteristics of tumors were systematically assessed. Furthermore, detailed prognostic information of the patients was collected through telephone follow-up.</div></div><div><h3>Results</h3><div>Among the 13 patients diagnosed with DCCS, there were 5 males and 8 females, with a mean age of 32.7 years. Tumors were predominantly located in the distal extremities. 3 patients had a prior history of trauma or surgery, while bone destruction was identified in 5 cases via imaging examinations. Grossly, the tumors appeared as grayish-white or white nodules with a hard texture. Microscopically, 2 tumors involved both the dermis and epidermis, while the other 11 were confined to the dermis. Tumor cells were arranged in nests, fascicles, sheets, mainly spindle-shaped or epithelioid in morphology. \"Wreath-like\" multinucleated giant cells were observed in 3 cases, and collagenous fibrous septa were present in the stroma of all tumors. All tumors showed diffuse expression of S100 or SOX10, and HMB-45, Melan-A, and MITF were positive to varying degrees. EWSR1 (22q12) gene breakage was detected by fluorescence in situ hybridization (FISH) in all 10 tested cases. Among the cases examined by next-generation sequencing (NGS), 2 had the EWSR1::ATF1 fusion gene and 1 had the EWSR1::CREB1 fusion gene.</div></div><div><h3>Conclusion</h3><div>DCCS is relatively rare in clinical practice. Its pathogenesis may be associated with a prior history of trauma or surgery; however, this potential association requires further validation through the accumulation of additional cases. Given the overlaps in morphological and immunohistochemical features between DCCS and other tumors exhibiting melanocytic differentiation, molecular testing (including the detection of EWSR1 gene rearrangement or specific fusion genes detection) holds significant value for the accurate diagnosis of primary DCCS.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156213"},"PeriodicalIF":3.2,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Managing cancer in autoimmune patients: Overcoming therapeutic challenges and expanding treatment options","authors":"Simran Singh,&nbsp;Asmita Das","doi":"10.1016/j.prp.2025.156212","DOIUrl":"10.1016/j.prp.2025.156212","url":null,"abstract":"<div><div>The intricate interplay between cancer and autoimmune diseases (ADs) is rooted in immune dysregulation, where genetic susceptibility, chronic inflammation, epigenetic modifications, and immunosuppressive therapies contribute to tumorigenesis. The dualistic nature of immune activation complicates therapeutic strategies, as immune checkpoint inhibitors and other immune-stimulatory therapies may exacerbate underlying ADs, leading to immune-related adverse events (irAEs), including organ toxicity, dermatologic reactions, and disease flares. Conversely, immunosuppressive treatments aimed at controlling ADs can compromise anti-tumor immunity and reduce the efficacy of cancer therapies. This necessitates a precision-medicine approach that balances effective tumor control with mitigation of immune-mediated complications. This review explores current therapeutic challenges and opportunities in managing cancer patients with pre-existing autoimmune conditions. Emphasis is placed on alternative treatment modalities, including targeted therapies such as kinase inhibitors (e.g., sorafenib), and adoptive cellular therapies like CAR-T and CAR-NK cells, which exhibit selective tumor targeting with a potentially reduced risk of irAEs. Moreover, natural compounds with dual immunomodulatory and antitumor properties offer a promising therapeutic avenue due to their multi-targeting capabilities and favorable safety profiles. Through case-based analysis, we highlight strategies that simultaneously address tumor progression and autoimmune dysregulation, underscoring the need for integrated, individualized therapeutic regimens in this complex patient population.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156212"},"PeriodicalIF":3.2,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}