Journal of Pathology Clinical Research最新文献

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148078078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148078079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148066021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148066067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","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}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148093041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preservation of cell-free RNA in percutaneous core-needle biopsy specimens' supernatants from non-small cell lung cancer improves genomic testing performance","authors":"Sheng Xu,&nbsp;Yi-Dan Ma,&nbsp;Zhi-Xin Bie,&nbsp;Jing-Yu Huang,&nbsp;Yuan-Ming Li,&nbsp;Zheng Wang,&nbsp;Xiao-Guang Li","doi":"10.1002/2056-4538.70081","DOIUrl":"10.1002/2056-4538.70081","url":null,"abstract":"<p>This prospective single-center study aimed to investigate whether preserving cell-free ribonucleic acid (cfRNA) in specimens' supernatants (SS) obtained from percutaneous core-needle biopsy (CNB) of non-small cell lung cancer (NSCLC) can improve the performance of genomic testing. Forty-three NSCLC patients who underwent image-guided CNB were enrolled. The SS from each CNB specimen was divided into two parts: one was mixed 1:1 with a cfRNA-protective solution, and the other was left unhandled. For quantitative analysis, 30 patients (regardless of mutation status) were evaluated by comparing cfRNA yield between cfRNA-protected and -unprotected SS. For qualitative analysis, 15 patients with fusion gene alterations were assessed by comparing genotyping results from cfRNA-protected SS to those from paired CNB specimens. Pneumothorax was the most frequent adverse event in CNB procedures, occurring in 20.9% of cases (9/43). No one experienced severe adverse events. In the quantitative analysis, 90.0% (27/30) of cfRNA-protected SS yielded adequate cfRNA, significantly higher than 53.3% (16/30) in cfRNA-unprotected SS (<i>p</i> &lt; 0.01). In the qualitative analysis, despite ineffective cfRNA preservation in three cases, DNA-level mutations were still detected in both the CNB specimens and cfRNA-protected SS. The overall concordance of genotyping results between cfRNA-protected SS and paired CNB specimens was 100%, correctly identifying all <i>ALK</i> fusions, <i>ROS1</i> rearrangements, and <i>MET-14</i> skipping alterations. These findings highlight that preserving cfRNA in CNB-SS from NSCLC can improve the performance of genomic testing, particularly for RNA-based assays, without compromising the accuracy of DNA-based assays.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12945666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147311672","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}