Pathology, research and practice最新文献

{"title":"The future of PCOS management: Disease modification through regenerative, metabolic, and digital therapeutics","authors":"Ruhi Arisha ,&nbsp;Shivam Sengupta ,&nbsp;Hitesh Kumar Dewangan ,&nbsp;Abdulaziz S. Saeedan ,&nbsp;Mohd Nazam Ansari ,&nbsp;Summya Rashid","doi":"10.1016/j.prp.2026.156397","DOIUrl":"10.1016/j.prp.2026.156397","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS) represents the leading endocrine problem affecting women of reproductive age, leading to serious complications related to reproduction, metabolism, and psychosocial aspects. Nonetheless, due to the heterogeneous nature and complex pathophysiology associated with PCOS, this condition remains uncaptured or undertreated as it often gets diagnosed at an advanced age due to its prevalence. The pathophysiology associated with PCOS involves the combination of genetic factors, resistance, neuroendocrine imbalance, as well as environmental factors that contribute towards hyperandrogenism, ovulation defects, and metabolic disorders as well. Hence, a comprehensive literature survey was conducted using PubMed, Scopus, Web of Science, and Google Scholar, prioritizing international clinical guidelines, meta-analyses, randomized controlled trials, systematic reviews, and high-quality preclinical studies that covered publications from 2015 to 2025, with the search terms being keywords specific to the disease. At present, the treatments such as lifestyle correction, combined oral pills, and anti-insulin therapies along with anti-androgen drugs only have symptomatic roles with no impact on the underlying mechanism associated with PCOS. However, new therapeutic modalities have been proposed from the past few years that is addressed by this narrative review, including mesenchymal stem cell-based therapies, microbiome therapies, as well as second-generation pharmacotherapies such as GLP-1 agonists and SGLT2 inhibitors. This is being complemented by equal developments in artificial intelligence and the learning process. However, there is work that needs to be done in relation to harmonizing the criteria for diagnosis and the long-term safety and accessibility of effective treatments. Moving forward, the focus should be placed on phenotype-based, precision, and multidisciplinary treatments of PCOS, along with emphasizing the necessity of sturdy clinical validation before worldwide adoption.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"280 ","pages":"Article 156397"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157664","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":"The role of sleep deprivation in prostate cancer and a preliminary exploration of its mechanisms","authors":"Jialong Zhang ,&nbsp;Lexing Yang ,&nbsp;Jun He ,&nbsp;Weiyi Li,&nbsp;Hongzhi Wang,&nbsp;Chaozhao Liang","doi":"10.1016/j.prp.2026.156379","DOIUrl":"10.1016/j.prp.2026.156379","url":null,"abstract":"<div><div>Previous studies suggested the link between sleep deprivation and prostate cancer, but its impact on disease progression is unclear. Moreover, clarifying this relationship could offer insights into prostate cancer mechanisms and potential treatments. In the present study, questionnaire and sleep monitoring of prostate cancer patients indicate that worse sleep quality correlates with higher Gleason scores. Subsequently, to study the effects of sleep deprivation in vivo, a sleep deprivation mouse model was established. Our findings show that sleep deprivation could accelerate tumor growth. Then, we performed transcriptome sequencing to infer the underlying mechanism. RNA sequencing found inflammation related pathways were activated in the sleep deprivation model. Moreover, we identified CXCL13 as a key mediator of sleep deprivation induced prostate progression. And inhibition of CXCR5, the receptor of CXCL13, reduced its tumor promoting effects. Molecular mechanism studies showed that CXCL13 enhanced cancer cell proliferation via activating JNK signaling pathway. In summary, our findings suggest that sleep deprivation may accelerate prostate cancer progression by activating the CXCL13/CXCR5/JNK signaling axis. These results provide preliminary insights into a potential therapeutic direction.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"280 ","pages":"Article 156379"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146070985","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":"Curcumin nanoparticles attenuate sepsis-induced myocardial injury by modulating the Nrf2/HO-1/SLC7A11/GPX4 and ACSL4/LPCAT3 pathways","authors":"Yuhang Wang ,&nbsp;Han Zhang ,&nbsp;Jiaqi Liu ,&nbsp;Rimei Lin ,&nbsp;Yingyu Huang ,&nbsp;Xinrui Liu ,&nbsp;Yunqi Dong ,&nbsp;Hongkui Lu ,&nbsp;Yutong Wei ,&nbsp;Haoze Lv ,&nbsp;Xinyu Liu ,&nbsp;Cong Sun","doi":"10.1016/j.prp.2026.156385","DOIUrl":"10.1016/j.prp.2026.156385","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Sepsis-Induced Myocardial Injury (SIMI) poses a serious threat to patients' lives. Although curcumin (Cur) has potential therapeutic effects on SIMI, its clinical application is hindered by the limitation of low bioavailability. The emergence of nanodelivery systems provides novel strategies to address this issue. This study aimed to investigate the therapeutic effects of curcumin nanoparticles (Cur-NPs) on septic myocarditis (SIMI) and its potential molecular mechanisms.</div></div><div><h3>Materials and methods</h3><div>Cur-NPs were prepared using the ion cross-linking method, and a septicemia mouse model was established by intraperitoneal injection of lipopolysaccharide (LPS). Immunofluorescence, Western blot (WB), real-time quantitative PCR (RT-qPCR), and other molecular biology techniques were employed to systematically explore the molecular mechanisms underlying the therapeutic effects of Cur-NPs on SIMI.</div></div><div><h3>Results</h3><div>Cur-NPs significantly alleviated myocardial tissue damage induced by septicemia and effectively mitigated inflammatory responses and mitochondrial damage. Mechanistic studies revealed that Cur-NPs upregulated the expression levels of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2), Heme Oxygenase-1 (HO-1), Solute Carrier Family 7 Member 11 (SLC7A11), Glutathione Peroxidase 4 (GPX4), Ferroptosis-suppressor-protein 1 (FSP1), and ferritin, while downregulating the expression of Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4), LysoPHosPHatidylcholine Acyltransferase 3 (LPCAT3), and 4-hydroxynonenal (4-HNE), thereby inhibiting ferroptosis in cardiomyocytes.</div></div><div><h3>Conclusions</h3><div>Cur-NPs can effectively alleviate SIMI by dual regulation of the Nrf2/HO-1/xCT/GPX4 pathway and the ACSL4/LPCAT3 pathway, providing a promising new approach for the clinical treatment of SIMI.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"280 ","pages":"Article 156385"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090216","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":"Exosome precision engineering: A comprehensive method for targeted gene and drug delivery","authors":"Hailah M. Almohaimeed ,&nbsp;Hadeel Abdulrahman Waggas ,&nbsp;Osama Mohammed Abdulaziz Altowaijri ,&nbsp;Jawaher A. Abdulhakim ,&nbsp;Zuhair M. Mohammedsaleh ,&nbsp;Amany I. Almars ,&nbsp;Aniruddha Chatterjee ,&nbsp;Bikram Dhara ,&nbsp;Daniel Ejim Uti","doi":"10.1016/j.prp.2026.156369","DOIUrl":"10.1016/j.prp.2026.156369","url":null,"abstract":"<div><div>Exosomes are small vesicles which cells use to communicate with one another by way of transporting proteins, lipids and nucleic acids. They are promising vectors that can be applied in the delivery of drugs and genes to locations because of their natural compatibility with the body, stability, and capability to go through biological barriers. Recent advances in the field of exosome &amp; synthetic biology resulted in new engineering strategies expanding their applicability to therapeutic applications. Scientists can target their surfaces with ligands, antibodies, or peptides to enhance accuracy of targeting, and through the development of more sophisticated loading methods- remote loading, stimuli responsive systems- nucleic acids and small molecules can be delivered effectively. Genetically engineered exosomes can deliver CRISPR/Cas9 available in biological therapy to modify immune responses and invent novel cancer-treatment options. However, high-level production, safety of the immune issues and regulatory approval are still challenges that should be overcome. The review explains the newest approaches and the issues that are yet to be resolved and emphasizes the potential that engineered exosomes can offer as versatile platforms to facilitate precision medicine and treatment of diseases.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"280 ","pages":"Article 156369"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090215","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":"Pathological mechanisms of hepatic ischemia-reperfusion injury and stem cell–based therapeutic strategies: Mechanistic insights and translational perspectives","authors":"Ru Nie ,&nbsp;Yunlong Duan ,&nbsp;Xiaoting Cao ,&nbsp;Mingquan Pang ,&nbsp;Zhixin Wang ,&nbsp;Haining Fan","doi":"10.1016/j.prp.2026.156382","DOIUrl":"10.1016/j.prp.2026.156382","url":null,"abstract":"<div><div>Hepatic ischemia–reperfusion injury (HIRI) remains a major clinical challenge in liver surgery, transplantation, and trauma, contributing to graft dysfunction and increased morbidity. This review summarizes the complex pathophysiology of HIRI, including metabolic derangements during ischemia, bursts of oxidative stress on reperfusion, and sterile inflammation driven by reactive oxygen species (ROS) and immune-cell activation. It also examines regulated cell death pathways—apoptosis, pyroptosis, necroptosis, and ferroptosis—that interact to create self-reinforcing cycles and further amplify tissue injury.Building on these mechanistic insights, the review highlights emerging therapeutic strategies centered on mesenchymal stem cells (MSCs) and MSC-derived products, including extracellular vesicles (EVs), exosomes, and conditioned medium. MSCs confer protection through immunomodulatory effects, such as promoting macrophage polarization toward anti-inflammatory phenotypes, as well as through cytoprotective mechanisms including antioxidant secretion and mitochondrial transfer. In addition, MSCs support tissue repair by enhancing regenerative responses. Preclinical studies consistently show that MSC-based interventions reduce oxidative stress, inflammation, and cell death. Early clinical trials in liver transplantation further suggest that MSC therapy is safe and may reduce ischemia-associated complications.Finally, this review discusses key translational barriers, including inefficient homing, donor-to-donor variability, and the need for standardized manufacturing and potency assessment. Future directions include MSC preconditioning, EV engineering, and combination approaches with machine perfusion technologies. By integrating mechanistic understanding with therapeutic advances, this review underscores the potential of MSC-based therapies to reshape HIRI management and highlights broader opportunities for regenerative medicine in organ injury.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"280 ","pages":"Article 156382"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090290","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":"Macrophage-associated immune-stromal crosstalks correlate with the tumor microenvironment in microsatellite-stable mucinous colorectal cancer","authors":"Yinjun He ,&nbsp;Tianneng Zhu ,&nbsp;Mingyu Zheng ,&nbsp;Qingxin Yu ,&nbsp;Siqin Lei ,&nbsp;Chaoyi Chen ,&nbsp;Dianhe Yu ,&nbsp;Zhiyong Liang ,&nbsp;Honghe Zhang","doi":"10.1016/j.prp.2026.156371","DOIUrl":"10.1016/j.prp.2026.156371","url":null,"abstract":"<div><div>Mucinous adenocarcinoma (MAC) of the colorectum is increasingly recognized as a subtype characterized by an immunosuppressive tumor microenvironment and poor response to immunotherapy, yet its immune and stromal landscape remains incompletely defined. In this study, we integrated three publicly available single-cell RNA sequencing datasets to comprehensively profile the cellular ecosystem of microsatellite-stable (MSS) MAC. Compared to classical adenocarcinoma (AC), MAC exhibited a distinct tumor microenvironment marked by elevated infiltration of myeloid and fibroblast populations, along with reduced lymphocyte and epithelial cell proportions. Notably, MAC harbored abundant immunosuppressive neutrophils that interacted intensively with interstitial resident tissue macrophage-like tumor-associated macrophages (RTM-TAMs) through IL1B–IL1R2 and CXCL8–CXCR2 signaling pathways, related to a pro-tumor myeloid network. Fibroblast analysis revealed a significant enrichment of VEGFA⁺ myofibroblastic cancer-associated fibroblasts (myCAFs), particularly in hypoxic, mucin-rich tumor regions, which were spatially associated with RTM-TAMs via SPP1–CD44/ITGA5/ITGB1 interactions. Leveraging cell-type-specific genes and key ligand–receptor pairs, we developed a Mucinous Colorectal cancer Immune Module (MCIM) comprising 18 genes, which stratified patient prognosis and was associated with overall survival in colorectal cancer cohorts. Together, these findings provide a detailed map of the immune-stromal architecture in MAC with MSS status, reveal macrophage-associated immunosuppressive features, and propose MCIM as a potential biomarker for prognostication in mucinous colorectal cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156371"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011538","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":"Performance of the VENTANA FOLR1 Assay for folate receptor alpha: Real-world evidence from 313 Chinese participants","authors":"Xiaoyan Chen ,&nbsp;Li Jiang ,&nbsp;Liangyan Ruan ,&nbsp;Teng Yu ,&nbsp;Weiwei Rui ,&nbsp;Yue Fan ,&nbsp;Huafeng Wang ,&nbsp;He Jiang ,&nbsp;Chaofu Wang","doi":"10.1016/j.prp.2026.156359","DOIUrl":"10.1016/j.prp.2026.156359","url":null,"abstract":"<div><div>Folate receptor-α is an ideal precision therapy target of ovarian cancer. The standardization of FRα assay and interpretative criteria is essential for ensuring diagnostic consistency and enhancing clinical efficacy in therapeutic applications. This study aims to analytically verify and evaluate the clinical performance of the VENTANA FOLR1 Assay. This real-world study of Chinese patients analyzed FRα expression using the VENTANA FOLR1 RxDx assay in 313 samples from diverse anatomical sites. Inter- and intra-observer agreement in FRα scoring was evaluated, and correlations between FRα positivity and clinicopathological parameters were examined. Three pathologists demonstrated excellent inter- and intra-observer agreement (&gt; 97 %) in FOLR1 interpretation. 40.9 % of cases showed high FRα expression, with a significantly higher positivity rate in high-grade serous carcinoma among the Chinese cohort. Primary tumors exhibited higher FRα positivity than metastatic lesions (44.2 % vs 32.2 %, p = 0.04). Chemotherapy exposure did not significantly alter FRα positivity across ovarian, fallopian tube, and primary peritoneal cancers, remained comparable to that of the overall cohort (41.2 % vs 40.9 %). Excision/resection samples were identified as optimal for FRα assessment. Our findings demonstrate the high reliability of the VENTANA FOLR1 Assay in Chinese clinical settings. Additionally, we conducted a systematic investigation into the associations between FRα expression and clinicopathological characteristics, highlighting its capacity to reflect FRα heterogeneity, maintain stability in post-chemotherapy FRα expression across various tumor types, and achieve robust performance in excision/resection samples. These findings underscore the value of standardizing FRα testing to improve patient selection for FRα-targeted MIRV therapies in China.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156359"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145928822","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":"DDB2 promotes epithelial-mesenchymal transition through activating NF-κB pathway in glioma","authors":"Jiuru Guo ,&nbsp;Wenjian Zhao ,&nbsp;Yaqin Hu ,&nbsp;Chenchen Zhou ,&nbsp;Haiyan Cao ,&nbsp;Guolian Xue ,&nbsp;Yueyang Mou ,&nbsp;Zhicheng Fan ,&nbsp;Yunpeng Kou ,&nbsp;Peigang Ji ,&nbsp;Min Chao ,&nbsp;Liang Wang","doi":"10.1016/j.prp.2026.156368","DOIUrl":"10.1016/j.prp.2026.156368","url":null,"abstract":"<div><div>Glioblastoma (GBM), the most prevalent primary brain tumor, is characterized by rapid proliferation, invasive growth patterns, and poor clinical outcomes. This study investigates the expression and clinical significance of DNA damage-binding protein 2(DDB2) in GBM, aiming to identify potential prognostic biomarkers and therapeutic targets. In this study, we demonstrated that DDB2 expression was negatively associated with patient prognosis in GBM patients. DDB2 knockdown inhibited the proliferation, invasion, and migration capacity of U87 and LN229 cells. In vivo, DDB2 knockdown inhibited the growth of xenograft tumors derived from inoculated GBM cells. DDB2 knockdown inhibited epithelial-mesenchymal transition (EMT) in U87 and LN229 cells. Mechanistically, DDB2 down-regulation led to the inhibition of nuclear translocation of P65 subunit, which inhibited the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway and resulted in the reduced expression of EMT-related transcription factors. Taken together, the present study demonstrates that DDB2 promotes EMT by activating the NF-κB pathway in GBM. These findings provide new insights into the role of DDB2 in GBM, suggesting that DDB2 could serve as a potential therapeutic target and prognostic marker for this malignancy.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156368"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023919","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":"Indomethacin alleviates acute pancreatitis by restoring autophagic flux via the AMPK signaling pathway","authors":"Lijun Lou ,&nbsp;Jing Li ,&nbsp;Yan Li ,&nbsp;Jiaming Feng ,&nbsp;Jun Yu ,&nbsp;Zeyu Wang ,&nbsp;Chao Zhang ,&nbsp;Liyu Chen ,&nbsp;Yuanhang Zhao ,&nbsp;Yongzhan Nie ,&nbsp;Liyan Li ,&nbsp;Yanglin Pan","doi":"10.1016/j.prp.2026.156377","DOIUrl":"10.1016/j.prp.2026.156377","url":null,"abstract":"<div><div>Acute pancreatitis (AP) remains a significant clinical challenge lacking early, targeted pharmacological interventions to prevent disease progression. Dysfunctional autophagy is a central pathogenic mechanism in AP. While indomethacin (IND), a nonsteroidal anti-inflammatory drug, is known to prevent post-ERCP pancreatitis, its broader therapeutic potential and underlying mechanisms in other forms of AP are unclear. Emerging evidence suggests that IND has the potential to activate autophagy. This study aimed to investigate whether IND protects against AP by regulating autophagy. We established cerulein (CER)-induced AP models both in vivo and in AR42J cells to evaluate the protective effects of IND. Transcriptomic and pathway analyses were conducted to identify underlying signaling mechanisms. Our results demonstrate that IND alleviated CER-induced pancreatic injury, as indicated by improved histopathological scores, reduced serum amylase and lipase levels, diminished inflammatory cell infiltration, and attenuated acinar cell cytotoxicity. Mechanistically, transcriptomic and experimental data revealed that IND restored autophagy via activation of the AMP-activated protein kinase (AMPK) signaling pathway. Critically, the protective effects of IND were abolished by either the autophagy inhibitor chloroquine or the AMPK inhibitor Compound C (CC). In conclusion, our findings suggest that IND may serve as a promising therapeutic candidate for the treatment of AP.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156377"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078735","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":"Renal cell carcinoma with biphasic morphology: A cohort showing similar morphology but distinct clinicopathological and molecular features","authors":"Ye Liao ,&nbsp;Xin Wang ,&nbsp;Zhenhua Zhang ,&nbsp;Xinyi Shen ,&nbsp;Peng Su ,&nbsp;Daochen Chong ,&nbsp;Yanxia Jiang ,&nbsp;Yujun Li ,&nbsp;Wei Zhang ,&nbsp;Wenjuan Yu","doi":"10.1016/j.prp.2026.156360","DOIUrl":"10.1016/j.prp.2026.156360","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Biphasic morphology, characterized by small cells clustered around basement membrane material, is a distinctive feature of &lt;em&gt;TFEB&lt;/em&gt;-rearranged renal cell carcinoma (RCC). However, other RCC subtypes may exhibit similar histological characteristics. Clinicopathological data from 12 cases of RCC with biphasic morphology—including four cases of &lt;em&gt;TFEB&lt;/em&gt;-rearranged RCC, four cases of &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCC, and four cases of chromophobe RCC (ChRCC)—were collected. Most of the 12 patients survived without complications, except for one patient with ChRCC who died accidentally 25 months after surgery. Microscopically, all 12 tumors showed varying proportions of biphasic morphology, comprising clear or eosinophilic large cells arranged in nests, glandular, or papillary structures, and clustered small cells forming pseudorosette structures around basement membrane-like deposits. Large pale cells with clear to foamy cytoplasm were observed in the four ChRCC tumors. IHC revealed consistent nuclear and cytoplasmic expression of TFEB in all four cases of &lt;em&gt;TFEB&lt;/em&gt;-rearranged RCC and diffuse nuclear positivity of TFE3 in &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCC. Cathepsin K and GPNMB were expressed in most &lt;em&gt;TFEB&lt;/em&gt;- and &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCCs, whereas the melanocytic markers Melan A and HMB45 were expressed to varying degrees. Additionally, PD-L1 (22C3) was expressed with a high CPS of approximately 90 in two cases of &lt;em&gt;TFEB&lt;/em&gt;-rearranged RCC. CK7, CD117, and Ksp-cad were expressed in both large and small cells in the four cases of ChRCC. FISH identified TFEB rearrangement in all four cases of &lt;em&gt;TFEB&lt;/em&gt;-rearranged RCC and TFE3 rearrangement in all four cases of &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCC. RNA sequencing and whole-exome sequencing revealed &lt;em&gt;TFEB&lt;/em&gt;–&lt;em&gt;MALAT1&lt;/em&gt; fusion in all four cases of &lt;em&gt;TFEB&lt;/em&gt;-rearranged RCC. &lt;em&gt;TFE3&lt;/em&gt;–&lt;em&gt;SFPQ&lt;/em&gt; fusion was detected in two cases, and &lt;em&gt;TFE3&lt;/em&gt;–&lt;em&gt;MED15&lt;/em&gt; fusion in the other two &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCC cases. PD-L1 (22C3) expression was detected in three cases of &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCC, two &lt;em&gt;TFE3&lt;/em&gt;-&lt;em&gt;MED15&lt;/em&gt; fusion subtype showed a CPS of approximately 30 and 20, whereas one &lt;em&gt;TFE3&lt;/em&gt;-&lt;em&gt;SFPQ&lt;/em&gt; fusion subtype showed a CPS of approximately 5. Additionally, in the four ChRCC cases, multiple segments of chromosomes 1, 2, 6, 8, 9, 10, and 17 were either lost or amplified. The biphasic structure with small cell components in RCC is observed in &lt;em&gt;TFEB&lt;/em&gt;-rearranged RCC and in &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCC and ChRCC, which may be prone to misdiagnosis based solely on morphology. Patients with &lt;em&gt;TFEB&lt;/em&gt;- and &lt;em&gt;TFE3&lt;/em&gt;-rearranged RCCs exhibiting small cell components tend to be younger and have more favorable prognoses. The &lt;em&gt;TFE3&lt;/em&gt;–&lt;em&gt;MED15&lt;/em&gt; gene fusion in RCC with a biphasic structure containing small cell components has been reported here for the first time. Genetic alterations in ChRCC with small cell components ","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"279 ","pages":"Article 156360"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980040","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}