Pub Date : 2025-12-17DOI: 10.1016/j.prp.2025.156337
Xiaoxi Wang , Xiaochen Shen , Moxuan Yang , Ling Yang , Ying He , Yanni Ren , Shuhao Wang , Dayi Wu , Yuanyuan Guo , Yiru Niu , Kaiyue Peng , Zhihui Wang , Jingpeng Wu , Jiacheng Li , Wei Wang , Feng Wang , Lijuan Cui , Wei Wang , Congrong Liu , Dingrong Zhong
Uterine smooth muscle tumors (USMTs) are the most common tumors of the female reproductive system, but remain diagnostically challenging due to morphological overlap among leiomyosarcoma (LMS), various leiomyoma (LM) subtypes, and smooth muscle tumors of uncertain malignant potential (STUMP). This study aimed to develop a weakly supervised artificial intelligence (AI) model for classifying USMTs as benign or malignant using only slide-level labels. A multi-center dataset comprising 94 LMS cases (408 whole-slide images, WSIs) and 634 benign cases (1389 WSIs) was used for model training and internal testing, with an independent external test set including 27 LMS cases (54 WSIs) and 90 benign cases (248 WSIs). The CAMEL2-based model achieved excellent diagnostic performance, with AUCs of 0.9976 and 0.9889 on the internal and external test sets, respectively, and accuracies exceeding 0.97. Heatmaps frequently highlighted regions enriched for key pathological features of LMS, while benign tissues were consistently assigned low-suspicion regions. In STUMP cases, heatmaps emphasized morphologically suspicious regions that often overlapped with areas identified by pathologists, supporting their potential as decision-support visualizations. In the AI–human collaboration study, model assistance was associated with improved diagnostic accuracy and reduced diagnostic time. This represents the first weakly supervised learning model for USMT diagnosis, achieving high accuracy and interpretability with minimal annotation requirements.
{"title":"An interpretable model based on weakly supervised learning for uterine smooth muscle tumor diagnosis: A multi-center study","authors":"Xiaoxi Wang , Xiaochen Shen , Moxuan Yang , Ling Yang , Ying He , Yanni Ren , Shuhao Wang , Dayi Wu , Yuanyuan Guo , Yiru Niu , Kaiyue Peng , Zhihui Wang , Jingpeng Wu , Jiacheng Li , Wei Wang , Feng Wang , Lijuan Cui , Wei Wang , Congrong Liu , Dingrong Zhong","doi":"10.1016/j.prp.2025.156337","DOIUrl":"10.1016/j.prp.2025.156337","url":null,"abstract":"<div><div>Uterine smooth muscle tumors (USMTs) are the most common tumors of the female reproductive system, but remain diagnostically challenging due to morphological overlap among leiomyosarcoma (LMS), various leiomyoma (LM) subtypes, and smooth muscle tumors of uncertain malignant potential (STUMP). This study aimed to develop a weakly supervised artificial intelligence (AI) model for classifying USMTs as benign or malignant using only slide-level labels. A multi-center dataset comprising 94 LMS cases (408 whole-slide images, WSIs) and 634 benign cases (1389 WSIs) was used for model training and internal testing, with an independent external test set including 27 LMS cases (54 WSIs) and 90 benign cases (248 WSIs). The CAMEL2-based model achieved excellent diagnostic performance, with AUCs of 0.9976 and 0.9889 on the internal and external test sets, respectively, and accuracies exceeding 0.97. Heatmaps frequently highlighted regions enriched for key pathological features of LMS, while benign tissues were consistently assigned low-suspicion regions. In STUMP cases, heatmaps emphasized morphologically suspicious regions that often overlapped with areas identified by pathologists, supporting their potential as decision-support visualizations. In the AI–human collaboration study, model assistance was associated with improved diagnostic accuracy and reduced diagnostic time. This represents the first weakly supervised learning model for USMT diagnosis, achieving high accuracy and interpretability with minimal annotation requirements.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156337"},"PeriodicalIF":3.2,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798004","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}
Pub Date : 2025-12-16DOI: 10.1016/j.prp.2025.156335
Han Wang , You-Wen Qian , Xia Sheng , Chun-Yan Xia , Hong-Zhen Chen , Zhen-Yu Cao , Hua Yu , Ying-Ying Zhou , Wen-Ming Cong , Miao-Xia He , Hui Dong
Background
Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) lacks standardized pathological diagnostic paradigm. The significance of tumor necrosis in cHCC-CCA remains undefined. This study aimed to decipher its role and develop a practical grading system.
Methods
A multicenter analysis was conducted on 307 cHCC-CCA patients. Tumor necrosis was pathologically graded as: TN1 (no necrosis, N = 35), TN2 (focal necrosis; maximum diameter of a single focus ≤0.55 cm/one low-power field, N = 129), and TN3 (extensive necrosis; >0.55 cm, N = 143). Associations between tumor necrosis and clinicopathological features, recurrence-free survival (RFS), overall survival (OS), early RFS (≤2 years), and late RFS (>2 years) were assessed. The impact of postoperative adjuvant transarterial chemoembolization (PA-TACE) was also evaluated.
Results
Higher necrosis grades (TN2/TN3) were significantly associated with aggressive tumor characteristics, including larger tumor size, vascular invasion, and lymph node metastasis. TN3 patients had the worst median RFS (0.28 years) and OS (1.36 years), compared to TN2 (RFS: 0.68 years; OS: 2.64 years) and TN1 (RFS: 1.46 years; OS: not reached). The grading system was an independent prognostic factor for RFS, OS, and early RFS in multivariate analysis. PA-TACE significantly improved early RFS in the TN2/TN3 groups and RFS in the TN3 group specifically, but not in the TN1 group.
Conclusions
Tumor necrosis in cHCC-CCA indicates aggressive tumor biology and poorer outcomes. The proposed three-tier grading system provides robust prognostic stratification. PA-TACE benefits patients with significant necrosis (TN2/TN3), particularly in preventing early recurrence. Standardized assessment of tumor necrosis is recommended to optimize risk stratification and guide adjuvant therapy decisions for cHCC-CCA patients.
背景：肝细胞-胆管合并癌（cHCC-CCA）缺乏标准化的病理诊断模式。肿瘤坏死在cHCC-CCA中的意义尚不明确。本研究旨在解读其作用，并建立一套实用的分级体系。方法：对307例cHCC-CCA患者进行多中心分析。肿瘤坏死病理分级为：TN1（无坏死，N = 35）、TN2（局灶性坏死，单灶最大直径≤0.55 cm/一个低倍视场，N = 129）、TN3（广泛坏死，>0.55 cm, N = 143）。评估肿瘤坏死与临床病理特征、无复发生存期（RFS）、总生存期（OS）、早期RFS（≤2年）和晚期RFS （bb0 ~ 2年）之间的关系。术后辅助经动脉化疗栓塞（PA-TACE）的影响也进行了评估。结果：较高的坏死分级（TN2/TN3）与肿瘤的侵袭性特征显著相关，包括肿瘤大小较大、血管侵犯和淋巴结转移。与TN2 （RFS: 0.68年；OS: 2.64年）和TN1 （RFS: 1.46年；OS：未达到）相比，TN3患者的中位RFS（0.28年）和OS（1.36年）最差。在多变量分析中，分级系统是RFS、OS和早期RFS的独立预后因素。PA-TACE显著改善TN2/TN3组的早期RFS，特别是TN3组的RFS，但TN1组没有。结论：cHCC-CCA肿瘤坏死提示肿瘤生物学侵袭性，预后较差。建议的三层分级系统提供了可靠的预后分层。PA-TACE对显著坏死（TN2/TN3）患者有益，特别是在预防早期复发方面。建议对肿瘤坏死进行标准化评估，以优化风险分层，指导cHCC-CCA患者的辅助治疗决策。
{"title":"Deciphering the significance of tumor necrosis and developing a grading system in combined hepatocellular-cholangiocarcinoma: A multicenter pathological study","authors":"Han Wang , You-Wen Qian , Xia Sheng , Chun-Yan Xia , Hong-Zhen Chen , Zhen-Yu Cao , Hua Yu , Ying-Ying Zhou , Wen-Ming Cong , Miao-Xia He , Hui Dong","doi":"10.1016/j.prp.2025.156335","DOIUrl":"10.1016/j.prp.2025.156335","url":null,"abstract":"<div><h3>Background</h3><div>Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) lacks standardized pathological diagnostic paradigm. The significance of tumor necrosis in cHCC-CCA remains undefined. This study aimed to decipher its role and develop a practical grading system.</div></div><div><h3>Methods</h3><div>A multicenter analysis was conducted on 307 cHCC-CCA patients. Tumor necrosis was pathologically graded as: TN1 (no necrosis, N = 35), TN2 (focal necrosis; maximum diameter of a single focus ≤0.55 cm/one low-power field, N = 129), and TN3 (extensive necrosis; >0.55 cm, N = 143). Associations between tumor necrosis and clinicopathological features, recurrence-free survival (RFS), overall survival (OS), early RFS (≤2 years), and late RFS (>2 years) were assessed. The impact of postoperative adjuvant transarterial chemoembolization (PA-TACE) was also evaluated.</div></div><div><h3>Results</h3><div>Higher necrosis grades (TN2/TN3) were significantly associated with aggressive tumor characteristics, including larger tumor size, vascular invasion, and lymph node metastasis. TN3 patients had the worst median RFS (0.28 years) and OS (1.36 years), compared to TN2 (RFS: 0.68 years; OS: 2.64 years) and TN1 (RFS: 1.46 years; OS: not reached). The grading system was an independent prognostic factor for RFS, OS, and early RFS in multivariate analysis. PA-TACE significantly improved early RFS in the TN2/TN3 groups and RFS in the TN3 group specifically, but not in the TN1 group.</div></div><div><h3>Conclusions</h3><div>Tumor necrosis in cHCC-CCA indicates aggressive tumor biology and poorer outcomes. The proposed three-tier grading system provides robust prognostic stratification. PA-TACE benefits patients with significant necrosis (TN2/TN3), particularly in preventing early recurrence. Standardized assessment of tumor necrosis is recommended to optimize risk stratification and guide adjuvant therapy decisions for cHCC-CCA patients.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156335"},"PeriodicalIF":3.2,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794214","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}
Pub Date : 2025-12-16DOI: 10.1016/j.prp.2025.156334
Shangomitra Bhattacharjee, Mahaboobkhan Rasool
Tissue inhibitors of matrix metalloproteinase 1 (TIMP-1) have recently attracted significant attention owing to their newly discovered cytokine function. These findings prompted a reevaluation of TIMP-1's role as an inhibitor of matrix metalloproteinase. Elevated TIMP-1 levels have been observed in various autoimmune conditions, influencing disease outcomes in multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis. Furthermore, TIMP-1 affects context-dependent metabolic profiles, enhances glycolytic turnover in monocytes, and is associated with ferroptosis in patients with rheumatoid arthritis. TIMP-1 also supports MHC-I expression and CD8 + T-cell activation, indicating a more active role in autoimmune conditions. Considering the expanding body of knowledge regarding TIMP-1 and its significant role in modifying metabolic profiles and disease outcomes, we carefully reviewed the contrasting functions of TIMP-1. Additionally, we summarize the upstream activators and signaling pathways involved in TIMP-1 activation and its reciprocal effects. Although TIMP-1 expression is linked to diverse disease outcomes, it is advisable to adopt a more nuanced approach to utilizing TIMP-1 depending on the specific disease context. This review proposes various strategies for targeting TIMP-1 as a therapeutic intervention to modulate the outcomes of autoimmune disorders.
{"title":"Harnessing the therapeutic potential of TIMP-1 in autoimmune inflammation: A prospective insight","authors":"Shangomitra Bhattacharjee, Mahaboobkhan Rasool","doi":"10.1016/j.prp.2025.156334","DOIUrl":"10.1016/j.prp.2025.156334","url":null,"abstract":"<div><div>Tissue inhibitors of matrix metalloproteinase 1 (TIMP-1) have recently attracted significant attention owing to their newly discovered cytokine function. These findings prompted a reevaluation of TIMP-1's role as an inhibitor of matrix metalloproteinase. Elevated TIMP-1 levels have been observed in various autoimmune conditions, influencing disease outcomes in multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis. Furthermore, TIMP-1 affects context-dependent metabolic profiles, enhances glycolytic turnover in monocytes, and is associated with ferroptosis in patients with rheumatoid arthritis. TIMP-1 also supports MHC-I expression and CD8 + T-cell activation, indicating a more active role in autoimmune conditions. Considering the expanding body of knowledge regarding TIMP-1 and its significant role in modifying metabolic profiles and disease outcomes, we carefully reviewed the contrasting functions of TIMP-1. Additionally, we summarize the upstream activators and signaling pathways involved in TIMP-1 activation and its reciprocal effects. Although TIMP-1 expression is linked to diverse disease outcomes, it is advisable to adopt a more nuanced approach to utilizing TIMP-1 depending on the specific disease context. This review proposes various strategies for targeting TIMP-1 as a therapeutic intervention to modulate the outcomes of autoimmune disorders.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156334"},"PeriodicalIF":3.2,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775383","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}
Pub Date : 2025-12-11DOI: 10.1016/j.prp.2025.156330
Peng Yu , Chen‑xi Li , Zhi‑qiang Song , Zhong‑cheng Gong
Synovitis of the temporomandibular joint (TMJ), a prevalent degenerative joint disease, plays an important role in the pathogenesis of TMJ osteoarthritis. This pathological condition arises from abnormal mechanical loading that induces a chronic low-grade inflammation within the synovial microenvironment through ferroptotic processes. Our research explores the impact of flow fluid-induced shear stress (FFSS) on ferroptosis in fibroblast-like synoviocytes (FLSs) and elucidates the relationship between mechanical overload and the development of TMJ synovitis. Experimental findings revealed progressive alterations in cellular morphology accompanied by significant elevations in intracellular ferrous ion (Fe2 +) concentrations and reactive oxygen species (ROS) levels with increasing FFSS intensity (all p < 0.05). Quantitative analysis showed upregulated expression of pro-inflammatory cytokines (IL-1β, IL-18), matrix-degrading enzymes (MMP-3, MMP-13), and ferroptosis-related markers (ACSL4, Nrf2), while antioxidant defense components (GPX4, system Xc-) were downregulated (all p < 0.05). Pharmacological inhibition using Ferrostatin-1 (Fer-1) significantly attenuated intracellular Fe2+ and ROS accumulation. The treatment group demonstrated reduced expression of IL-1β (p < 0.05) and ACSL4 (p < 0.001), with concomitant upregulation of GPX4 (p < 0.05) and Nrf2 (p < 0.001), though IL-18 modulation did not reach statistical significance (p > 0.05). These results establish that mechanical overload initiates ferroptosis in FLSs, driving inflammatory responses and extracellular matrix degradation through elevated Fe2+ and ROS production, ultimately contributing to TMJ synovitis pathogenesis. Our investigation provides novel mechanistic insights into FFSS-mediated ferroptosis in synovial cells, presenting foundational evidence for developing targeted therapeutic strategies that modulate this cell death pathway to enhance clinical management of TMJ synovitis.
{"title":"Effect of Ferrostatin-1 on temporomandibular joint synovitis induced by abnormal flow fluid shear stress: An in vitro study","authors":"Peng Yu , Chen‑xi Li , Zhi‑qiang Song , Zhong‑cheng Gong","doi":"10.1016/j.prp.2025.156330","DOIUrl":"10.1016/j.prp.2025.156330","url":null,"abstract":"<div><div>Synovitis of the temporomandibular joint (TMJ), a prevalent degenerative joint disease, plays an important role in the pathogenesis of TMJ osteoarthritis. This pathological condition arises from abnormal mechanical loading that induces a chronic low-grade inflammation within the synovial microenvironment through ferroptotic processes. Our research explores the impact of flow fluid-induced shear stress (FFSS) on ferroptosis in fibroblast-like synoviocytes (FLSs) and elucidates the relationship between mechanical overload and the development of TMJ synovitis. Experimental findings revealed progressive alterations in cellular morphology accompanied by significant elevations in intracellular ferrous ion (Fe<sup>2 +</sup>) concentrations and reactive oxygen species (ROS) levels with increasing FFSS intensity (all <em>p</em> < 0.05). Quantitative analysis showed upregulated expression of pro-inflammatory cytokines (IL-1β, IL-18), matrix-degrading enzymes (MMP-3, MMP-13), and ferroptosis-related markers (ACSL4, Nrf2), while antioxidant defense components (GPX4, system Xc-) were downregulated (all <em>p</em> < 0.05). Pharmacological inhibition using Ferrostatin-1 (Fer-1) significantly attenuated intracellular Fe<sup>2+</sup> and ROS accumulation. The treatment group demonstrated reduced expression of IL-1β (<em>p</em> < 0.05) and ACSL4 (<em>p</em> < 0.001), with concomitant upregulation of GPX4 (<em>p</em> < 0.05) and Nrf2 (<em>p</em> < 0.001), though IL-18 modulation did not reach statistical significance (<em>p</em> > 0.05). These results establish that mechanical overload initiates ferroptosis in FLSs, driving inflammatory responses and extracellular matrix degradation through elevated Fe<sup>2+</sup> and ROS production, ultimately contributing to TMJ synovitis pathogenesis. Our investigation provides novel mechanistic insights into FFSS-mediated ferroptosis in synovial cells, presenting foundational evidence for developing targeted therapeutic strategies that modulate this cell death pathway to enhance clinical management of TMJ synovitis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156330"},"PeriodicalIF":3.2,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145749026","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}
Pub Date : 2025-12-11DOI: 10.1016/j.prp.2025.156329
Jilong Qin , Longguang Li , Chi Sing Ng , Xiaodong Lin , Xina Lin , Peng Hou , Ping He
Objective
To explore the clinicopathological and immunohistochemical features of primary Rosai-Dorfman disease (RDD) in the lung and mediastinum.
Methods
Histological observation and immunohistochemical staining of 5 cases of pulmonary and mediastinal RDD, with a review of the related literature.
Results
Two cases were located in the trachea with involvement of the lung. One case was located in the left lower lung. Two cases were located in the mediastinum. Macroscopically, 1 case had clear boundaries, while 4 cases had unclear boundaries, and grayish-white on cut surfaces. Microscopically, low power view showing alternating light and dark areas. The dark areas comprise an admixture of lymphocytes and plasma cells. The light areas comprise the characteristic pale pink histiocytic cells. Histiocytes are large with round-to-oval nuclei, dispersed chromatin, prominent nucleoli, and abundant clear-to-foamy or vacuolated cytoplasm. Emperipolesis was observed in all five cases. All five cases showed interstitial fibrosis or sclerosis and Russell bodies. Four cases (4/5, 80 %) showed lymphoid follicles with germinal centers in the interstitium. Four cases showed (4/5, 80 %) interstitial neutrophil infiltration, with three cases accompanied by microabscess formation. Immunophenotypically, the histiocytes expressed Cyclin D1(5/5, 100 %), OCT2 (5/5, 100 %), S100 protein (5/5, 100 %), CD68 (5/5, 100 %), CD163 (5/5, 100 %), BCL2 (5/5, 100 %) and CD30 (3/5, 60 %), but did not express CD1a, Langerin, IgG4 and ALK.
Conclusion
RDD of the lung and mediastinum is rare, with a wide range of ages. Histologically, there are often lymphoid follicles with germinal centers and interstitial fibrosis or sclerosis. This together with the expression of BCL2 and CD30 in the histiocytes can lead to misdiagnosis of lymphomas or other lymphoproliferative diseases or missed diagnosis, particularly in the mediastinum. Careful histological examination for the diagnostic feature of emperipolesis together with characteristic Cyclin D1, OCT2, S100 protein, and CD68 positivity are important clues for accurate diagnosis.
{"title":"Primary Rosai-Dorfman disease of lung and mediastinum: A clinicopathological and immunohistochemical study of five cases","authors":"Jilong Qin , Longguang Li , Chi Sing Ng , Xiaodong Lin , Xina Lin , Peng Hou , Ping He","doi":"10.1016/j.prp.2025.156329","DOIUrl":"10.1016/j.prp.2025.156329","url":null,"abstract":"<div><h3>Objective</h3><div>To explore the clinicopathological and immunohistochemical features of primary Rosai-Dorfman disease (RDD) in the lung and mediastinum.</div></div><div><h3>Methods</h3><div>Histological observation and immunohistochemical staining of 5 cases of pulmonary and mediastinal RDD, with a review of the related literature.</div></div><div><h3>Results</h3><div>Two cases were located in the trachea with involvement of the lung. One case was located in the left lower lung. Two cases were located in the mediastinum. Macroscopically, 1 case had clear boundaries, while 4 cases had unclear boundaries, and grayish-white on cut surfaces. Microscopically, low power view showing alternating light and dark areas. The dark areas comprise an admixture of lymphocytes and plasma cells. The light areas comprise the characteristic pale pink histiocytic cells. Histiocytes are large with round-to-oval nuclei, dispersed chromatin, prominent nucleoli, and abundant clear-to-foamy or vacuolated cytoplasm. Emperipolesis was observed in all five cases. All five cases showed interstitial fibrosis or sclerosis and Russell bodies. Four cases (4/5, 80 %) showed lymphoid follicles with germinal centers in the interstitium. Four cases showed (4/5, 80 %) interstitial neutrophil infiltration, with three cases accompanied by microabscess formation. Immunophenotypically, the histiocytes expressed Cyclin D1(5/5, 100 %), OCT2 (5/5, 100 %), S100 protein (5/5, 100 %), CD68 (5/5, 100 %), CD163 (5/5, 100 %), BCL2 (5/5, 100 %) and CD30 (3/5, 60 %), but did not express CD1a, Langerin, IgG4 and ALK.</div></div><div><h3>Conclusion</h3><div>RDD of the lung and mediastinum is rare, with a wide range of ages. Histologically, there are often lymphoid follicles with germinal centers and interstitial fibrosis or sclerosis. This together with the expression of BCL2 and CD30 in the histiocytes can lead to misdiagnosis of lymphomas or other lymphoproliferative diseases or missed diagnosis, particularly in the mediastinum. Careful histological examination for the diagnostic feature of emperipolesis together with characteristic Cyclin D1, OCT2, S100 protein, and CD68 positivity are important clues for accurate diagnosis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156329"},"PeriodicalIF":3.2,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145749025","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}
Precision medicine has transformed healthcare by tailoring treatment plans to an individual’s genetic profile, in contrast to standardized therapies. Patient-derived tumoroids facilitate cancer research, while extracellular vesicles (EVs) provide insights into disease states. EVs from tumoroids serve as diagnostic tools for cancer, reflecting gene mutations and enabling minimally invasive tracking of disease progression. Artificial Intelligence (AI) enhances precision medicine by analyzing extensive datasets derived from tumors and EVs, thereby advancing cancer detection and therapy. The tumor microenvironment (TME) plays a pivotal role in tumor development and is studied using patient-derived organoids (PDOs), which accurately recapitulate tissue function and support drug screening and personalized treatment strategies. Integrating precision medicine with AI-driven analysis of tumoroids and EVs holds the potential to improve patient outcomes and quality of life through personalized treatment approaches.
{"title":"Tumoroid-derived extracellular vesicles for prognosis and therapeutics: A valuable tool in precision medicine","authors":"Vijay Murali Ravi Mythili , ArulJothi Kandasamy Nagarajan , Vasanth Kanth Loganathbabu Thasma , Shriya Pattabiram , Kumaran Kasinathan , Ramya Lakshmi Rajendran , Anand Krishnan , Prakash Gangadaran , Byeong-Cheol Ahn","doi":"10.1016/j.prp.2025.156332","DOIUrl":"10.1016/j.prp.2025.156332","url":null,"abstract":"<div><div>Precision medicine has transformed healthcare by tailoring treatment plans to an individual’s genetic profile, in contrast to standardized therapies. Patient-derived tumoroids facilitate cancer research, while extracellular vesicles (EVs) provide insights into disease states. EVs from tumoroids serve as diagnostic tools for cancer, reflecting gene mutations and enabling minimally invasive tracking of disease progression. Artificial Intelligence (AI) enhances precision medicine by analyzing extensive datasets derived from tumors and EVs, thereby advancing cancer detection and therapy. The tumor microenvironment (TME) plays a pivotal role in tumor development and is studied using patient-derived organoids (PDOs), which accurately recapitulate tissue function and support drug screening and personalized treatment strategies. Integrating precision medicine with AI-driven analysis of tumoroids and EVs holds the potential to improve patient outcomes and quality of life through personalized treatment approaches.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156332"},"PeriodicalIF":3.2,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145749027","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}
Pub Date : 2025-12-11DOI: 10.1016/j.prp.2025.156331
Shan Wang , Lin Qin , Xiaoli Song , Hejia Yin , Weihong Yang , Robabe Bazesh
Introduction
Fenofibrate (FenoF) has demonstrated potential in regulating glycemia and lipid profiles across various metabolic disorders. However, its effects on the offspring of rats with gestational diabetes mellitus (GDM) have not yet been investigated. This study aims to evaluate the long-term effects of FenoF on glycemic control, lipid metabolism, liver histology, and the expression of key metabolic and inflammatory proteins in the offspring of GDM-exposed rats.
Materials and methods
Pregnant Wistar rats were randomly assigned to four groups (n = 4 per group): Control, GDM, FenoF-treated (100 mg/kg/day, orally), and GDM rats treated with FenoF (GDM + FenoF). Diabetes was induced via a single intraperitoneal injection of streptozotocin (50 mg/kg) on gestational day 12. Six male offspring from each group were randomly selected and maintained on a standard chow diet. The offspring were reared until adulthood (12 weeks of age), at which point plasma glucose levels, lipid profiles, and liver tissue alterations were evaluated through histopathological analysis and Western blotting.
Results
FenoF treatment significantly reduced triglyceride, low-density lipoprotein cholesterol (LDL-C), and glucose levels (P < 0.05), while significantly increasing high-density lipoprotein cholesterol (HDL-C) levels (P < 0.05) in the offspring of GDM rats. FenoF exerted an ameliorative effect in GDM rat offspring, as evidenced by a significant reduction in hepatic TNF-α expression (P < 0.001) and a marked increase in PPARα levels (P < 0.001) compared to the untreated GDM group. Western blot analysis revealed that FenoF treatment significantly downregulated TLR4 and NF-κB expression, indicating attenuation of inflammatory signaling. Moreover, FenoF treatment significantly upregulated AKT1, IRS1, and CPT1A levels, suggesting enhanced insulin signaling and lipid metabolism. Additionally, Histopathological analysis demonstrated that FenoF preserved liver architecture and significantly reduced inflammation and structural abnormalities relative to GDM controls.
Conclusion
In the context of gestational diabetes, FenoF appears to be a promising therapeutic candidate for improving glucose and lipid homeostasis, protecting hepatic tissue from diabetes-induced damage and inflammation, and enhancing key metabolic pathways in the offspring of GDM rats.
{"title":"Long-term effects of fenofibrate in male offspring of gestational diabetic rats: Evaluation of glycemia, lipid profiles, liver tissue, and metabolic alterations","authors":"Shan Wang , Lin Qin , Xiaoli Song , Hejia Yin , Weihong Yang , Robabe Bazesh","doi":"10.1016/j.prp.2025.156331","DOIUrl":"10.1016/j.prp.2025.156331","url":null,"abstract":"<div><h3>Introduction</h3><div>Fenofibrate (FenoF) has demonstrated potential in regulating glycemia and lipid profiles across various metabolic disorders. However, its effects on the offspring of rats with gestational diabetes mellitus (GDM) have not yet been investigated. This study aims to evaluate the long-term effects of FenoF on glycemic control, lipid metabolism, liver histology, and the expression of key metabolic and inflammatory proteins in the offspring of GDM-exposed rats.</div></div><div><h3>Materials and methods</h3><div>Pregnant Wistar rats were randomly assigned to four groups (n = 4 per group): Control, GDM, FenoF-treated (100 mg/kg/day, orally), and GDM rats treated with FenoF (GDM + FenoF). Diabetes was induced via a single intraperitoneal injection of streptozotocin (50 mg/kg) on gestational day 12. Six male offspring from each group were randomly selected and maintained on a standard chow diet. The offspring were reared until adulthood (12 weeks of age), at which point plasma glucose levels, lipid profiles, and liver tissue alterations were evaluated through histopathological analysis and Western blotting.</div></div><div><h3>Results</h3><div>FenoF treatment significantly reduced triglyceride, low-density lipoprotein cholesterol (LDL-C), and glucose levels (P < 0.05), while significantly increasing high-density lipoprotein cholesterol (HDL-C) levels (P < 0.05) in the offspring of GDM rats. FenoF exerted an ameliorative effect in GDM rat offspring, as evidenced by a significant reduction in hepatic TNF-α expression (P < 0.001) and a marked increase in PPARα levels (P < 0.001) compared to the untreated GDM group. Western blot analysis revealed that FenoF treatment significantly downregulated TLR4 and NF-κB expression, indicating attenuation of inflammatory signaling. Moreover, FenoF treatment significantly upregulated AKT1, IRS1, and CPT1A levels, suggesting enhanced insulin signaling and lipid metabolism. Additionally, Histopathological analysis demonstrated that FenoF preserved liver architecture and significantly reduced inflammation and structural abnormalities relative to GDM controls.</div></div><div><h3>Conclusion</h3><div>In the context of gestational diabetes, FenoF appears to be a promising therapeutic candidate for improving glucose and lipid homeostasis, protecting hepatic tissue from diabetes-induced damage and inflammation, and enhancing key metabolic pathways in the offspring of GDM rats.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156331"},"PeriodicalIF":3.2,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775393","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}
Pub Date : 2025-12-08DOI: 10.1016/j.prp.2025.156328
Maxime Golias , Zuzana Krupova , Pierre Defrenaix , Marie-Françoise Heymann , Dominique Heymann
Intratumoral heterogeneity is a real challenge for understanding the key mechanisms involved in cancer progression, but also for pathologists to make a reliable diagnosis. The development of precision medicine in oncology allows each treatment to be tailored to the specific characteristics of the tumours. However, the ability to isolate pure cell populations is a very difficult task and makes accurate analysis difficult. The development since the 90’s of precise dissection techniques, known as microdissection, has helped to overcome problems associated with tumor heterogeneity. Since then, a few techniques have been developed that provide dissection accuracy down to the sub-cellular level. These technologies have enabled key principles to be understood in basic research but handling difficulties have prevented their use in pathology laboratories. Working with microquantities can also be a difficult task and requires several technical adaptations. This review provides an overview of all microdissection techniques currently available. In addition to their main advantages, examples of applications and adaptations of molecular biology techniques to microquantities are proposed to illustrate the interest of these technical approaches in both basic research and clinical applications.
{"title":"Microdissection: Insights and progress in the era of precision medicine","authors":"Maxime Golias , Zuzana Krupova , Pierre Defrenaix , Marie-Françoise Heymann , Dominique Heymann","doi":"10.1016/j.prp.2025.156328","DOIUrl":"10.1016/j.prp.2025.156328","url":null,"abstract":"<div><div>Intratumoral heterogeneity is a real challenge for understanding the key mechanisms involved in cancer progression, but also for pathologists to make a reliable diagnosis. The development of precision medicine in oncology allows each treatment to be tailored to the specific characteristics of the tumours. However, the ability to isolate pure cell populations is a very difficult task and makes accurate analysis difficult. The development since the 90’s of precise dissection techniques, known as microdissection, has helped to overcome problems associated with tumor heterogeneity. Since then, a few techniques have been developed that provide dissection accuracy down to the sub-cellular level. These technologies have enabled key principles to be understood in basic research but handling difficulties have prevented their use in pathology laboratories. Working with microquantities can also be a difficult task and requires several technical adaptations. This review provides an overview of all microdissection techniques currently available. In addition to their main advantages, examples of applications and adaptations of molecular biology techniques to microquantities are proposed to illustrate the interest of these technical approaches in both basic research and clinical applications.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156328"},"PeriodicalIF":3.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743735","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}
Pub Date : 2025-12-07DOI: 10.1016/j.prp.2025.156327
Linlin Huang , Jing Li , Huawen Wang , Mei Tang , Min Jing , Xinyi Shi , Yongkun Xiao , Lu Bai , Ling Wang , Dong Liu , Tao Wu , Chao Ding , Jinglong Lv , Huami Ye , Jing Li , Jiamei Fan , Pengchun Wu , Wenbo Zhou , Xiaohui Wu , Hongwei Wang
Background
Angioimmunoblastic T-cell lymphoma (AITL), a subtype of nodal T-follicullar helper (TFH) cell lymphoma, may pccasionally contain Hodgkin/Reed-Sternberg (HRS)-like cells, which poses significant diagnostic challenges. These large atypical cells ofthen express CD30 and weak PAX5, making classical Hodgkin lymphoma (CHL) and increasing the risk of misdiagnosis. Accurate recognition requires integration of histological, immunophenotypic, viral, and molecular features.
Method
We retrospectively analyzed 11 patients diagnosed with AITL containing HRS-like cells between January 2020 and January 2025. All cases were consultation cases from a regional lymphoma diagnostic center, with available formalin-fixed, paraffin-embedded lymph node tissue. A comprehensive review included histomorphology, immunohistochemistry, Epstein-Barr virus-encoded RNA (EBER) in situ hybridization, T-cell receptor (TCR) and immunoglobulin (IG) gene rearrangement studies, and targeted next-generation sequencing (NGS) of lymphoma-associated genes.
Results
The cohort included 7 men and 4 women, with a median age of 63 years. Histologically, all cases showed partial to complete effacement of nodal architecture, proliferation of high endothelial venules, expansion of follicular dendritic cell (FDC) meshworks, and scattered HRS-like cells. Immunophenotypically, HRS-like cells were consistently CD30-positive, weak PAX5-positive (9/11), and variably CD15-positive. Background T cells expressed TFH markers including CD4, PD-1, CD10, BCL-6, CXCL13, and ICOS. EBER was positive in 10 cases. TCR gene clonality was detected in 9 patients, while 2 also showed B-cell clonality. NGS identified frequent mutations in TET2 (11/11) and RHOA (8/11), with additional alterations in DNMT3A, KMT2D, CREBBP, BRD4, and PLCG1.
Conclusions
AITL with HRS-like cells is prone to misdiagnosis as CHL due to overlapping morphological and immunophenotypic features. Integration of EBER, TCR/IG clonality assessment, and molecular profiling, particularly the identification of TET2 and RHOA mutations is essential for accurate classification. Recognizing this entity is critical for avoiding diagnostic pitfalls and guiding appropriate therapeutic strategies.
{"title":"Nodal T-follicular helper cell lymphoma with hodgkin/reed-sternberg-like cells: Clinicopathologic and molecular characterization of 11 cases","authors":"Linlin Huang , Jing Li , Huawen Wang , Mei Tang , Min Jing , Xinyi Shi , Yongkun Xiao , Lu Bai , Ling Wang , Dong Liu , Tao Wu , Chao Ding , Jinglong Lv , Huami Ye , Jing Li , Jiamei Fan , Pengchun Wu , Wenbo Zhou , Xiaohui Wu , Hongwei Wang","doi":"10.1016/j.prp.2025.156327","DOIUrl":"10.1016/j.prp.2025.156327","url":null,"abstract":"<div><h3>Background</h3><div>Angioimmunoblastic T-cell lymphoma (AITL), a subtype of nodal T-follicullar helper (TFH) cell lymphoma, may pccasionally contain Hodgkin/Reed-Sternberg (HRS)-like cells, which poses significant diagnostic challenges. These large atypical cells ofthen express CD30 and weak PAX5, making classical Hodgkin lymphoma (CHL) and increasing the risk of misdiagnosis. Accurate recognition requires integration of histological, immunophenotypic, viral, and molecular features.</div></div><div><h3>Method</h3><div>We retrospectively analyzed 11 patients diagnosed with AITL containing HRS-like cells between January 2020 and January 2025. All cases were consultation cases from a regional lymphoma diagnostic center, with available formalin-fixed, paraffin-embedded lymph node tissue. A comprehensive review included histomorphology, immunohistochemistry, Epstein-Barr virus-encoded RNA (EBER) in situ hybridization, T-cell receptor (TCR) and immunoglobulin (IG) gene rearrangement studies, and targeted next-generation sequencing (NGS) of lymphoma-associated genes.</div></div><div><h3>Results</h3><div>The cohort included 7 men and 4 women, with a median age of 63 years. Histologically, all cases showed partial to complete effacement of nodal architecture, proliferation of high endothelial venules, expansion of follicular dendritic cell (FDC) meshworks, and scattered HRS-like cells. Immunophenotypically, HRS-like cells were consistently CD30-positive, weak PAX5-positive (9/11), and variably CD15-positive. Background T cells expressed TFH markers including CD4, PD-1, CD10, BCL-6, CXCL13, and ICOS. EBER was positive in 10 cases. TCR gene clonality was detected in 9 patients, while 2 also showed B-cell clonality. NGS identified frequent mutations in <em>TET2</em> (11/11) and <em>RHOA</em> (8/11), with additional alterations in <em>DNMT3A, KMT2D, CREBBP, BRD4</em>, and <em>PLCG1</em>.</div></div><div><h3>Conclusions</h3><div>AITL with HRS-like cells is prone to misdiagnosis as CHL due to overlapping morphological and immunophenotypic features. Integration of EBER, TCR/IG clonality assessment, and molecular profiling, particularly the identification of <em>TET2</em> and <em>RHOA</em> mutations is essential for accurate classification. Recognizing this entity is critical for avoiding diagnostic pitfalls and guiding appropriate therapeutic strategies.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156327"},"PeriodicalIF":3.2,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743809","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}
Pub Date : 2025-12-06DOI: 10.1016/j.prp.2025.156326
Min Tang , Pengpeng Xu , Xiaogang Zhang
Glioblastoma (GBM) has been an aggressive brain tumor and it demonstrates poor prognosis and resistance to the traditional therapeutics. GBM is characterized by abnormal proliferation, high growth, and a significantly immunosuppressive tumor microenvironment (TME), making immunotherapy as an ideal treatment for GBM. The recent advances in the field of immunotherapy such as vaccines, and CAR-T cell treatments, have demonstrated significant efficacy in accelerating anticancer immune responses and improving survival outcomes. Immune checkpoint drugs targeting CTLA-4 and PD-1/PD-L1 have demonstrated synergistic effects in enhancing T cell activation and infiltration. Vaccines such as DCVax-L and oncolytic viruses including G47Δ have demonstrated promising outcomes in the clinical studies. CAR-T cell treatments have been directed against particular antigens such as EGFRvIII and IL13Rα2 and have demonstrated considerable antitumor efficacy. Nonetheless, there are a number of challenges to be considered including the immunosuppressive TME, the blood-brain barrier (BBB), and the molecular heterogeneity of GBM. Addressing these challenges requires a versatile strategy, encompassing the development of innovative combination drugs, complicated imaging methodologies to evaluate treatment efficacy, and the discovery of biomarkers to predict patient responses to immunotherapy. The future research can focus on highlighting the complicated connections between the immune system and GBM, utilizing perspectives from preclinical models and clinical studies to formulate more effective and customized treatment options. This review emphasizes on the recent research results and clinical data, providing insights into prospective developments in GBM immunotherapy and highlighting the necessity of a comprehensive strategy to enhance patient outcomes.
{"title":"Advancing glioblastoma immunotherapy: Molecular pathways and innovative therapeutic strategies","authors":"Min Tang , Pengpeng Xu , Xiaogang Zhang","doi":"10.1016/j.prp.2025.156326","DOIUrl":"10.1016/j.prp.2025.156326","url":null,"abstract":"<div><div>Glioblastoma (GBM) has been an aggressive brain tumor and it demonstrates poor prognosis and resistance to the traditional therapeutics. GBM is characterized by abnormal proliferation, high growth, and a significantly immunosuppressive tumor microenvironment (TME), making immunotherapy as an ideal treatment for GBM. The recent advances in the field of immunotherapy such as vaccines, and CAR-T cell treatments, have demonstrated significant efficacy in accelerating anticancer immune responses and improving survival outcomes. Immune checkpoint drugs targeting CTLA-4 and PD-1/PD-L1 have demonstrated synergistic effects in enhancing T cell activation and infiltration. Vaccines such as DCVax-L and oncolytic viruses including G47Δ have demonstrated promising outcomes in the clinical studies. CAR-T cell treatments have been directed against particular antigens such as EGFRvIII and IL13Rα2 and have demonstrated considerable antitumor efficacy. Nonetheless, there are a number of challenges to be considered including the immunosuppressive TME, the blood-brain barrier (BBB), and the molecular heterogeneity of GBM. Addressing these challenges requires a versatile strategy, encompassing the development of innovative combination drugs, complicated imaging methodologies to evaluate treatment efficacy, and the discovery of biomarkers to predict patient responses to immunotherapy. The future research can focus on highlighting the complicated connections between the immune system and GBM, utilizing perspectives from preclinical models and clinical studies to formulate more effective and customized treatment options. This review emphasizes on the recent research results and clinical data, providing insights into prospective developments in GBM immunotherapy and highlighting the necessity of a comprehensive strategy to enhance patient outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"278 ","pages":"Article 156326"},"PeriodicalIF":3.2,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743703","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}
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