Journal of Pathology Clinical Research最新文献

{"title":"Reduced folate receptor alpha (FOLR1) protein expression in fallopian tubes from premenopausal women: implications for the FOLR1 CDx assay for mirvetuximab-soravtansine therapy.","authors":"Annika Nasdala, Leonie D Kandt, Martin Radner, Nora Schaumann, Malte Gronewold, Pia Hillmann, Henriette Christgen, Jens Hachenberg, Elna Kuehnle, Christian Hartmann, Matthias Christgen","doi":"10.1002/2056-4538.70091","DOIUrl":"https://doi.org/10.1002/2056-4538.70091","url":null,"abstract":"<p><p>Mirvetuximab-soravtansine (MIRV-S) is an antibody-drug conjugate targeting folate receptor alpha (FOLR1). MIRV-S is approved for the treatment of FOLR1-positive, platinum-resistant ovarian carcinoma. Patient eligibility is determined by immunohistochemistry (IHC) using a companion diagnostic (CDx) assay (FOLR1-2.1, Ventana). This assay requires on-slide positive controls (OPCs) to aid FOLR1 evaluation. The manufacturer recommends normal fallopian tube (NFT) tissue for OPCs. Estrogen receptor signaling represses FOLR1 in cell culture models. It is unknown whether hormonal factors, such as menopausal status, also impact on FOLR1 immunoreactivity in NFTs used as OPCs. To address this question, we studied FOLR1 protein expression in NFTs (n = 51) from women aged 26-83 years. IHC was performed with the FOLR1-2.1 CDx assay. Immunoreactivity at apical and basolateral cell membranes was assessed using H-scores (aH-score and bH-score respectively). Overall FOLR1 expression was evaluated using a combined H-score (cH-score; i.e. aH- and bH-scores added together). Immunoreactivity scores in pre-, peri-, and postmenopausal age groups were compared with the chi-square test for trends. NFTs showed variable FOLR1 protein expression [median aH-score: 152.5, interquartile range (IQR): 120-175; median bH-score: 35, IQR: 7-85; median cH-score: 195, IQR: 140-245]. Apical immunoreactivity was age-independent (p = 0.619), but low or absent basolateral immunoreactivity (bH-score <35) was associated with premenopausal age (p = 0.018). Low overall FOLR1 expression (cH-score <195) was also associated with premenopausal age (p = 0.037). In conclusion, NFTs show an age-dependent FOLR1 expression pattern, which likely reflects hormonal repression of FOLR1 in premenopausal women. NFT tissue from postmenopausal women is appropriate and meets the requirements for the current FOLR1 CDx assay.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 3","pages":"e70091"},"PeriodicalIF":3.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13103951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MET fusions and splicing variants in glioma: a landscape integrating clinical, pathological, and survival features","authors":"Zheng Fang,&nbsp;Chengjun Zheng,&nbsp;Peng Wang,&nbsp;Xing Liu,&nbsp;Lingyu Liu,&nbsp;Guanzhang Li,&nbsp;Jiahan Dong,&nbsp;Qiaodong Chen,&nbsp;Delong Zhang,&nbsp;Yutong Feng,&nbsp;Ying Zhang,&nbsp;Zhaoshi Bao","doi":"10.1002/2056-4538.70085","DOIUrl":"10.1002/2056-4538.70085","url":null,"abstract":"<p><i>MET</i> alterations, including <i>MET</i> fusions and splicing variants (F/SVs), are linked to glioma progression, but the clinical features remain underexplored since the 2021 WHO classification of tumors of the CNS. We aimed to systematically depict the <i>MET</i> F/SVs and patient characteristics in a multicenter cohort focusing on clinical, pathological, and survival features. We studied data from 1,041 patients with <i>MET</i> F/SVs data from the public Chinese Glioma Genome Atlas database and the TruSight Tumor 170 study. Clinical outcomes were evaluated based on the RANO criteria. We used chi-square and Fisher's exact tests for variable analysis. Kaplan–Meier analysis was used to assess survival trends, while univariate and multivariate analyses revealed the prognostic value of <i>MET</i> F/SVs. Immunohistochemical staining was performed to demonstrate the MET expression level. Among the 1,041 patients, 49 patients had F/SVs (4.70%), and 23 had ZM fusion (<i>PTPRZ1-MET</i> fusion gene; 2.21%). Among the 67 recurrent grade 4 astrocytomas, the proportions of F/SVs (11.94%, <i>n</i> = 8) and ZMs (5.97%, <i>n</i> = 4) were the highest. <i>MET</i> F/SVs were significantly associated with malignant clinical outcomes in the <i>IDH</i>-mutant astrocytoma cohort, with a frequency of 5.04% (18/357) across all WHO grades. Multivariate analysis revealed that the <i>MET</i> F/SVs were independently associated with worse survival in astrocytoma patients [overall survival (OS): <i>p</i> = 0.0011; progression-free survival (PFS): <i>p</i> = 0.004]. ZM fusion was associated with a worse prognosis in both astrocytoma (OS <i>p</i> &lt; 0.001, PFS <i>p</i> &lt; 0.001) and glioblastoma (OS, <i>p</i> = 0.252; PFS, <i>p</i> = 0.010) patients. We highlight the utmost relevance of ZM fusion as an adverse prognostic factor in astrocytoma (11/382, 2.88%) and glioblastoma grade 4 (11/401, 2.74%) patients and suggest that the grading of these tumors should be refined.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular subtype concordance and metastatic patterns in muscle-invasive bladder cancer","authors":"Csilla Olah,&nbsp;Dániel Juhász,&nbsp;Melinda Váradi,&nbsp;Henning Reis,&nbsp;Mulham Al-Nader,&nbsp;Osama Mahmoud,&nbsp;Barbara T. Grünwald,&nbsp;Viktor Grünwald,&nbsp;Boris Hadaschik,&nbsp;Péter Nyirády,&nbsp;Tibor Szarvas","doi":"10.1002/2056-4538.70088","DOIUrl":"10.1002/2056-4538.70088","url":null,"abstract":"<p>Molecular subtypes are potential prognostic and predictive tools in muscle-invasive bladder cancer (MIBC). However, subtype concordance between primary tumors and metastases, as well as subtype-specific differences in metastatic patterns, remain poorly characterized. The present study aimed to evaluate the concordance of molecular subtypes between primary tumors and matched lymph node (LN) metastases and to explore their association with metastatic patterns. Gene expression–based molecular subtypes were determined according to the five-tiered Lund Taxonomy in 182 primary tumor samples and 34 matched LN metastases from patients with MIBC who underwent upfront radical cystectomy. Subtypes identified in the primary tumors were compared with those in matched positive LNs and patterns of distant metastasis were analyzed. In addition, the association between molecular and histological subtypes was also investigated. We found an overall 62% subtype concordance between primary tumors and corresponding LN metastases, with complete concordance in the basal/squamous subtype, lower concordance in the luminal subtypes (genomically unstable: 67%; urothelial-like: 57%), and low concordance (33%) in the mesenchymal-like (Mes) subtype. Luminal subtypes were associated with LN-only metastases and less frequent distant metastases. In contrast, the Mes subtype was associated with a higher rate of distant metastases (43%), and more frequent multiorgan involvement (≥3 organs: 40%). Higher expression of the mesenchymal gene <i>CDH2</i> and the neuronal-differentiation genes <i>GNG4</i> and <i>ENO2</i> was associated with a higher number of metastatic sites. Gene expression–based molecular subtypes may change between primary MIBCs and matched LN metastases, and these differences appear to be subtype-dependent. Mes subtype and the expression of <i>CDH2</i> as well as <i>GNG4</i> and <i>ENO2</i> are associated with more frequent and extensive metastases, indicating highly aggressive forms of MIBC.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147532785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATM immunohistochemistry as an effective screening method for POLE variants among endometrial carcinomas lacking mismatch repair deficiency and p53 abnormalities","authors":"Xinyi Huang,&nbsp;Yingmei Wang,&nbsp;Wenjing Ni,&nbsp;Luyang Zhong,&nbsp;Yang Qin,&nbsp;Shujun Zeng,&nbsp;Hong Xu,&nbsp;Yuling Qu,&nbsp;Peizhen Hu,&nbsp;Jing Zhang","doi":"10.1002/2056-4538.70086","DOIUrl":"10.1002/2056-4538.70086","url":null,"abstract":"<p>The molecular classification of endometrial carcinomas (ECs) is now integrated into clinical practice. However, identification of polymerase-ε (<i>POLE</i>) variants remains reliant on DNA sequencing, which limits broader implementation. Given the strong prognostic value of pathogenic <i>POLE</i> mutations and the established efficacy of immunohistochemistry (IHC) for detecting mismatch repair (MMR) deficiency and p53 abnormalities, there is a clear need for IHC-based screening strategies to identify patients likely to carry <i>POLE</i> variants and prioritize them for confirmatory sequencing. In this study, we analyzed 24 cases with <i>POLE</i> pathogenic mutations (<i>POLE</i>mut ECs), 3 with benign <i>POLE</i> variants, and 32 matched cases with no specific molecular profile (NSMP) from a cohort of 378 ECs. IHC evaluation of the ataxia telangiectasia mutated (ATM) protein revealed that <i>POLE</i>-mutated ECs (with pathogenic or benign <i>POLE</i> variants) exhibited significantly higher frequencies of non-diffuse positive staining patterns, including null, heterogeneous positive, and subclonal loss, compared with NSMP cases. Targeted next-generation sequencing of all exons across 474 cancer-related genes in the 27 <i>POLE</i>-mutated ECs and 20 NSMP cases with ATM non-diffuse positive staining patterns confirmed that <i>POLE</i>-mutated ECs typically had high tumor mutational burden and were enriched for <i>ATM</i> truncating variants. <i>ATM</i> molecular alterations, including various variant subtypes and multisite mutations, also closely correlated with these staining patterns. Based on these findings, we refined the ATM IHC interpretation framework to integrate staining patterns with sequencing data for improved molecular correlation. Specifically, the null and subclonal loss patterns showed high specificity (96.9%), positive predictive value (94.1%), and accuracy (79.7%) for identifying <i>POLE</i> variants. Notably, the null pattern appeared exclusively in ECs with pathogenic <i>POLE</i> mutations. These results suggest that ATM IHC staining is an effective screening tool for identifying patients who may benefit from confirmatory <i>POLE</i> sequencing among those lacking MMR deficiency or p53 abnormalities.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147532788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Folate receptor alpha (FRα) expression in tubo-ovarian and endometrial tumors: a study of 923 cases","authors":"Isabela Töltési,&nbsp;Kristýna Němejcová,&nbsp;Michaela Kendall Bártů,&nbsp;Romana Vránková,&nbsp;David Cibula,&nbsp;Pavel Fabian,&nbsp;Filip Frühauf,&nbsp;Jitka Hausnerová,&nbsp;Jan Laco,&nbsp;Gábor Méhes,&nbsp;Zuzana Špůrková,&nbsp;Marián Švajdler,&nbsp;Radoslav Matěj,&nbsp;Pavel Dundr","doi":"10.1002/2056-4538.70087","DOIUrl":"10.1002/2056-4538.70087","url":null,"abstract":"<p>Folate receptor alpha (FRα) is a promising therapeutic target due to its high expression in several tumor types and its rare expression in healthy tissue. Recently, the antibody-drug conjugate mirvetuximab soravtansine has been approved for treatment of advanced platinum-resistant high-grade serous carcinoma (HGSC). Immunohistochemical expression of FRα has been extensively studied in HGSC, but most studies conducted before the clinical studies targeting FRα used variable antibodies and scoring criteria, which makes comparison of older literature data with recent studies difficult. Moreover, the data regarding its expression in other types of ovarian and other female genital tract tumors are limited or absent. In our study, we focused on immunohistochemical expression in 923 tubo-ovarian and endometrial tumors (assessed on tissue microarrays), using standardized scoring criteria and the VENTANA FOLR1 CDx assay. The results of our study showed the highest FRα expression in serous carcinomas, specifically HGSC (45% positive cases), followed by low-grade serous carcinoma (25%), endometrial serous carcinoma (11%), and serous borderline tumor (10%). Endometrioid and clear cell ovarian carcinomas showed rare positivity (2% and 1%, respectively). All other tumors examined were negative, including mucinous ovarian tumors, sex cord-stromal tumors, endometrial endometrioid carcinomas, undifferentiated and dedifferentiated carcinomas, and endometrial clear cell carcinomas. In conclusion, these results confirm that FRα expression in HGSC and LGSC reaches similar values compared to published data, and is present in a minority of endometrial serous carcinomas. In other ovarian and endometrial tumors examined, FRα expression is absent or rare.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147505256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Weakly supervised deep learning for cutaneous squamous and basal cell carcinoma in whole-slide histopathology","authors":"Anne Petzold,&nbsp;Anja Wessely,&nbsp;Stefan Schliep,&nbsp;Hong Jiang,&nbsp;Manuel Tran,&nbsp;Elias AT Koch,&nbsp;Tingying Peng,&nbsp;Hans Starz,&nbsp;Carola Berking,&nbsp;Carsten Marr,&nbsp;Markus V Heppt","doi":"10.1002/2056-4538.70082","DOIUrl":"10.1002/2056-4538.70082","url":null,"abstract":"<p>Distinguishing infiltrative basal cell carcinoma (BCC) from poorly differentiated cutaneous squamous cell carcinoma (cSCC) remains a significant histopathological challenge. Automated deep learning approaches hold promise for improving diagnostic reliability, yet robust external validation is essential. In this study, we developed a weakly supervised deep learning model to classify these diagnostically challenging subtypes and evaluated its generalizability across internal and external cohorts, as well as in comparison to a dermatopathology foundation model (HistoGPT). The model employed a multiple-instance learning framework (CLAM) using the histopathology-specific transformer Phikon for feature extraction from whole-slide images. Slide-level ground-truth diagnoses from the collected images (<i>n</i> = 335, University Hospital Erlangen) were derived from routine clinical practice and re-evaluated by two board-certified dermatopathologists. Performance was assessed on an internal test set of 84 whole-slide images (27 cSCC and 57 BCC) and two external datasets: Queensland cohort (<i>n</i> = 10, curated in-distribution cases) and the COBRA cohort (<i>n</i> = 200, broad, partly out-of-distribution cases). Model discrimination was quantified using ROC curves, while accuracy, sensitivity, and specificity were reported alongside 95% Wilson confidence intervals (CIs). On the internal test set, the model achieved perfect classification [area under the receiver operating characteristic (AUC) = 1.0; 100% accuracy, sensitivity, and specificity]. Similarly, strong performance was observed in the Queensland cohort (AUC = 1.0), although limited by sample size. In the more heterogeneous COBRA cohort, discrimination remained high (AUC = 0.923, 95% CI 0.885–0.961), requiring threshold adjustment to correct for marked calibration shift (balanced accuracy 86.5% at Youden's <i>J</i>). Attention heatmaps highlighted histologically meaningful regions. In zero-shot evaluation on the internal test set, HistoGPT achieved an overall accuracy of 77%, with high class-wise sensitivity for BCC (98%, 95% CI 91–100) but markedly reduced sensitivity for cSCC (33%, 95% CI 19–52). Fine-tuning a task-specific classifier on the HistoGPT backbone substantially improved performance, achieving near-perfect discrimination and 98% balanced accuracy. These findings demonstrate that weakly supervised deep learning enables highly accurate classification of diagnostically challenging BCC and cutaneous squamous cell carcinoma subtypes. However, reliable deployment across institutions necessitates careful calibration and domain adaptation, and even powerful foundation models such as HistoGPT benefit from targeted fine-tuning to ensure robust performance in dermatopathology.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147500384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial heterogeneity of antibody–drug conjugate targets in pancreatic ductal adenocarcinoma","authors":"Deema Sabtan,&nbsp;Marie-Lisa Eich,&nbsp;Florian Loch,&nbsp;Julen Karl Pérez Zuschneid,&nbsp;Markus Möbs,&nbsp;Judith Böhme,&nbsp;Frederick Klauschen,&nbsp;David Horst,&nbsp;Mihnea P Dragomir,&nbsp;Gabriel Dernbach,&nbsp;Simon Schallenberg","doi":"10.1002/2056-4538.70083","DOIUrl":"10.1002/2056-4538.70083","url":null,"abstract":"<p>Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, with limited therapeutic options, few patients showing targetable molecular changes. New therapeutic strategies are necessary. Antibody–drug conjugates (ADCs) have emerged as alternative therapeutic strategies across various cancer types. Herein, we analyze the expression and spatial heterogeneity (six cores per patients) of three ADC targets (c-MET, NECTIN4, and TROP-2) in a cohort of 62 PDAC patients (1,116 tissue cores) and associate their levels with clinicopathological and genomic parameters, and the expression of immune checkpoints. c-MET exhibited significantly higher expression at the tumor front versus tumor center, along with notable intratumoral heterogeneity. In contrast, NECTIN4 and TROP-2 displayed homogeneous expression patterns, with NECTIN4 being absent in approximately two-thirds of cases, while TROP-2 showed consistently strong positivity across tumor regions (98% 3+). By simulating sampling sufficiency for reliable scoring, we observed that, for c-MET, two tumor samples were sufficient to achieve a maximum score of 1+, while for higher scores (2+ and 3+), four samples were required. For NECTIN4, four samples were necessary to detect scores of 1+ and 2+. For TROP-2, for a 3+ score, just two samples were sufficient to reach the maximum score. c-MET or TROP-2 expression scores were not associated with any clinicopathological parameters. In contrast, NECTIN4 expression showed an association with tumor grade. Correlations with immune checkpoints revealed that high TROP-2 expression was inversely correlated with PD-L1 expression. For all three markers no significant differences in expression were found between <i>SMAD4</i> wild-type and <i>SMAD4</i>-mutated tumors, nor between <i>TP53</i> wild-type and <i>TP53</i>-mutated tumors. Furthermore, analysis of lymph node and distant (liver and peritoneal) metastases revealed significantly higher c-MET and NECTIN4 expression in the metastatic setting. In conclusion, TROP-2 is highly expressed in most PDACs, independent of clinicopathological and genomic parameters, and inversely correlating with PD-L1, making TROP-2 an ideal ADC target.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147469983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathologic and molecular landscape of villitis of unknown etiology: insights from a large-scale case–control study in PR China","authors":"Meiling Wang,&nbsp;Xiaorong Sun,&nbsp;Huayan Ren,&nbsp;Fengchun Gao,&nbsp;Xiangyu Sun,&nbsp;Chang Lu,&nbsp;Yanxue Yin,&nbsp;Juan Li,&nbsp;Chengquan Zhao","doi":"10.1002/2056-4538.70084","DOIUrl":"10.1002/2056-4538.70084","url":null,"abstract":"<p>Villitis of unknown etiology (VUE) is a chronic placental inflammatory lesion characterized by lymphohistiocytic infiltration and destruction of villous architecture in the absence of infection. Although VUE is well recognized for its association with fetal growth restriction and adverse pregnancy outcomes, its clinicopathologic correlates and molecular basis remain poorly understood. VUE cases were identified from the pathology database of Jinan Maternal and Child Health Hospital (2020–2023) and classified as high-grade or low-grade according to the Amsterdam criteria. Clinical data, maternal complications, and neonatal outcomes were collected from electronic medical records. Multivariable logistic regression was used to determine independent risk factors. RNA sequencing was performed on 28 placental samples (24 VUE and 4 controls) to identify differentially expressed genes and pathways. A total of 970 cases (381 high-grade and 589 low-grade) and 980 controls were included. VUE prevalence was 5.8%. Hypertensive disorders of pregnancy (HDP) were independently associated with VUE occurrence (odds ratio 1.67, 95% CI 1.28–2.19, <i>p</i> &lt; 0.001). VUE placentas frequently exhibited chronic intervillositis, chronic deciduitis, and avascular villi, whereas maternal vascular malperfusion showed no significant difference from controls. High-grade VUE was significantly associated with low-birth-weight, small-for-gestational-age infants, and increased neonatal intensive care unit admissions, indicating a severity-dependent impact on neonatal outcomes. Transcriptomic profiling revealed robust upregulation of interferon-inducible, cytotoxic, and chemokine genes – most notably <i>GBP5</i>, <i>CXCL9</i>, and <i>CXCL10</i> – with enrichment of interferon-γ, IL-6/JAK/STAT3, TNF-α/NF-κB, and antigen presentation pathways. VUE, particularly its high-grade form, is a significant placental lesion associated with HDP, adverse neonatal outcomes, and avascular villi. Its distinct interferon-rich molecular profile, consistent with a maternal anti-fetal T-cell–mediated process, underscores its clinical and biological importance. GBP5 emerges as a potential biomarker of interferon-driven inflammation, providing new mechanistic insight and diagnostic relevance for placental immune injury.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147470068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequent NPM1 mutation, monoblastic/monocytic origin and prognostic significance of organ and system involvement in myeloid sarcoma: a multicenter study","authors":"Alex Jenei,&nbsp;Béla Kajtár,&nbsp;Tamás László,&nbsp;Hazem A Juratli,&nbsp;Livia Vida,&nbsp;Ágota Szepesi,&nbsp;Réka Mózes,&nbsp;Botond Timár,&nbsp;Jörg Halter,&nbsp;Stefan Dirnhofer,&nbsp;Alexandar Tzankov","doi":"10.1002/2056-4538.70079","DOIUrl":"10.1002/2056-4538.70079","url":null,"abstract":"<p>Myeloid sarcoma (MS) is a tumorous extramedullary proliferation of blast or blast equivalent cells (e.g., promonocytes or promyelocytes). The most frequent cutaneous presentation is often referred to as leukemia cutis (LC). These lesions, especially without the clinical context of a known bone marrow disease, pose a differential diagnostic challenge. In this retrospective multicenter clinico-pathological study on 154 patients with MS or LC, 169 samples were analyzed by morphology, immunohistochemistry, and fluorescent <i>in situ</i> hybridization, and a subset by additional sequencing [<i>TP53</i>]. The majority of cases were lysozyme positive (diffuse in 91% and focal in 5%), 51% showed diffuse and 6% focal expression of CD56, and IRF8 was strongly positive in 31% of the lesions. Lack of myeloperoxidase (MPO), CD117, and CD34 expression was observed in 27%, 39%, and 58%, respectively. PU.1 was positive in almost all instances (95%), but BRAF V600E was consistently negative. CD123 was diffusely (13%) or focally (25%) positive, which, in addition to frequent CD4 (73%) and CD56 expression, pointed to a phenotypic overlap with blastic plasmacytoid dendritic cell neoplasms. Survival analysis revealed that MS occurring at sanctuary sites (CNS, orbit, ovary, and testis) was characterized by excellent survival. Similarly to histiocytoses, there was a prognostic difference between isolated and multisystemic involvement by MS. Patients who underwent allogeneic hematopoietic stem cell transplantation showed significantly improved survival. In conclusion, this multicenter study suggests that most MS are of myelomonocytic/monoblastic origin, a high proportion of them are <i>NPM1</i> mutated, and may lack expression of MPO and CD34. NPM1 mutation-specific antibodies should be integrated into the diagnostic panels for MS or LC, while IRF8 and PU.1 are not recommended as they cannot distinguish MS from histiocytic neoplasms.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12960061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147357275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI-derived prognostic biomarkers from melanoma whole slide image segmentation: an initial discovery and assessment","authors":"Emily L Clarke,&nbsp;Derek Magee,&nbsp;Julia Newton-Bishop,&nbsp;Gerald Saldanha,&nbsp;William Merchant,&nbsp;Marlous Hall,&nbsp;Robert Insall,&nbsp;Nigel G Maher,&nbsp;Richard A Scolyer,&nbsp;Grace Farnworth,&nbsp;Anisah Ali,&nbsp;Mark Bamford,&nbsp;Eva Sticova,&nbsp;Petr Kujal,&nbsp;Sally O'Shea,&nbsp;Darren Treanor","doi":"10.1002/2056-4538.70075","DOIUrl":"10.1002/2056-4538.70075","url":null,"abstract":"<p>The current melanoma staging system predicts 74% of the variance in survival, with prognostic biomarkers subject to high levels of inter-observer variation. This work assesses whether a previously developed convolutional neural network (CNN) for invasive melanoma segmentation in whole slide images (WSIs) may reveal new insights into melanoma morphology and patient prognosis. This paper uses Cox proportional multivariate regression analyses to evaluate the ability of the CNN outputs to predict patient survival across 745 WSIs from 5 data sources. Five objective histomorphological parameters of tumour size and shape that are independently associated with overall and melanoma-specific survival were created from the CNN: tumour area<i>(log)</i> (HR 1.48 CI 1.30–1.68, <i>p</i> &lt; 0.001), tumour perimeter<i>(log)</i> (HR 1.86 CI 1.48–2.32, <i>p</i> &lt; 0.001), major axis length<i>(log)</i> (HR 1.88 CI 1.42–2.48, <i>p</i> &lt; 0.001), Nodularity Index<i>(log)</i> (HR 1.77 CI 1.28–2.43, <i>p</i> &lt; 0.001) and digital Breslow thickness<i>(log)</i> (HR 2.04, CI 1.63–2.54, <i>p</i> &lt; 0.001). These results indicate that melanoma segmentation of the entire lesion within a WSI may be used to predict patient outcome. Moreover, this technology can be used to make new morphological discoveries to provide information not currently contained within our staging system (<i>e.g.</i> Nodularity Index), as well as provide objectivity and automation of current biomarkers (<i>e.g.</i> digital Breslow thickness). Further work is required to validate this initial discovery and evaluation.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147357297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}