Journal of Pathology Clinical Research最新文献

{"title":"A subset of high-grade sarcomas with myogenic differentiation are associated with recurrent FGFR fusions","authors":"Maximus CF Yeung,&nbsp;Carla Saoud,&nbsp;Sarah Chiang,&nbsp;Meera Hameed,&nbsp;Cristina R Antonescu","doi":"10.1002/2056-4538.70094","DOIUrl":"10.1002/2056-4538.70094","url":null,"abstract":"<p>Recurrent fusions involving <i>FGFR1-4</i> genes have been previously described in rare subsets of mostly benign chondroid and mesenchymal neoplasms involving bone and soft tissue. However, a more comprehensive analysis of sarcomas associated with <i>FGFR</i> fusions, including their incidence and histotypes, has not been performed. Triggered by an <i>FGFR1</i>-rearranged unclassified high-grade sarcoma with myogenic differentiation, we investigated our molecular database for sarcomas with <i>FGFR</i> gene fusions to assess their recurrent potential and morphologic spectrum. A total of six unclassified sarcomas were identified, occurring in five females and one male, with a median age of 66.5 years. Tumors were located in the uterus and retroperitoneal/trunk soft tissue. Histologically, all tumors were high grade, composed predominantly of spindle cell morphology with variable cytologic atypia, high mitotic activity, and areas of necrosis. By immunohistochemistry, all tumors demonstrated evidence of myogenic differentiation, with focal or diffuse positivity for one or more markers (desmin, h-caldesmon, smooth muscle actin). However, none of the cases displayed diagnostic features of leiomyosarcoma or other known pathologic entities. Molecular studies revealed recurrent fusions involving <i>FGFR1</i> (<i>n</i> = 3), <i>FGFR2</i> (<i>n</i> = 1), and <i>FGFR4</i> (<i>n</i> = 2), retaining the kinase domain. Additional recurrent genomic alterations included <i>TP53</i> mutations, <i>CDKN2A</i> homozygous deletions, and <i>RB1</i> alterations. Most patients followed an aggressive clinical course, including metastases and disease-related mortality. These findings expand the spectrum of sarcomas driven by <i>FGFR</i> gene fusions, underscoring the importance of molecular testing for accurate diagnosis and potential targeted therapy in high-grade sarcomas with myogenic features.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148018306","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":"Do all colorectal mucinous adenocarcinomas arise via the serrated neoplasia pathway?","authors":"Anne-Marie Vos,&nbsp;Peter H van Zwam,&nbsp;Natasja Rutgers,&nbsp;Shannon van Vliet,&nbsp;Elisa Vink-Börger,&nbsp;Rachel S van der Post,&nbsp;Femke Simmer,&nbsp;Iris D Nagtegaal","doi":"10.1002/2056-4538.70092","DOIUrl":"10.1002/2056-4538.70092","url":null,"abstract":"<p>Colorectal mucinous adenocarcinomas (MACs) and serrated adenocarcinomas (SACs) demonstrate considerable overlap in morphological and molecular features, suggesting a spectrum rather than two distinct tumour types. This study investigates the presence of serrated morphological features, precursors, and molecular features in a large cohort of MAC. The study includes 698 MAC collected via the Dutch nationwide pathology databank. Histological review and mismatch repair evaluation were performed on all cases. Next generation sequencing was performed on 396 cases. Multiplex nested methylation-specific PCR (MSP) was performed on 260 microsatellite stable (MSS) cases. The majority of tumours were right-sided (62.6%). Precursor lesions were identified in 9.6% of cases, 88% of which were serrated. Serrated morphology was present in 71% of MAC. Of all cases, 33.8% were microsatellite unstable (MSI). Half of the evaluated cases were CpG island methylator phenotype high. Tumours were divided into six molecular subcategories <i>BRAF</i>/MSS (9.8%), <i>BRAF</i>/MSI (24.7%), <i>KRAS</i>/MSS (38.6%), <i>KRAS</i>/MSI (4.3%), double wild-type/MSS (16.7%), and double wild-type/MSI (5.8%). Based on the presence of a serrated precursor, and/or serrated morphology, and/or a serrated molecular profile, 83.1% of MAC in our cohort could be classified as serrated-MAC. Serrated-MAC developed in older patients, was more often right-sided, showed less perineural invasion, and fewer nodal metastases, when compared to MAC-NOS. Survival analysis showed no significant difference between serrated-MAC and MAC-NOS. We have confirmed that a large majority of colorectal MAC have similar characteristics to SAC.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147983887","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 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148085717","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 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148074627","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":"The prognostic significance of the IASLC grading system in ALK-positive invasive non-mucinous adenocarcinoma of the lung: correlation with clinicopathological features","authors":"Dongmei Gu,&nbsp;Jie Bao,&nbsp;Hong Chen,&nbsp;Siyi Chen,&nbsp;Chenxi Shi,&nbsp;Xia Guo,&nbsp;Xiaoyu Zhou,&nbsp;Zhe Lei,&nbsp;Lingchuan Guo,&nbsp;Qianqian Yang","doi":"10.1002/2056-4538.70093","DOIUrl":"10.1002/2056-4538.70093","url":null,"abstract":"<p>The prognostic value of the International Association for the Study of Lung Cancer (IASLC) grading system in anaplastic lymphoma kinase (ALK)-positive invasive non-mucinous adenocarcinoma (INMA) remains unclear, particularly in relation to the tumor immune microenvironment (TIME). This retrospective study included 108 patients with ALK-positive INMA. Tumors were graded according to the IASLC system. Clinicopathological features, progression-free survival (PFS), and overall survival (OS) were analyzed. Immunohistochemistry was used to assess PD-L1 expression and tumor-infiltrating lymphocytes (TILs), including CD4+, CD8+, and FoxP3+ regulatory T cells. Associations were evaluated using Kaplan–Meier analysis, Cox regression models, and correlation analyses. Higher IASLC grades were significantly associated with more aggressive pathological features, elevated PD-L1 expression, and shorter progression-free survival (PFS). Higher-grade tumors exhibited enhanced T-cell infiltration, predominantly driven by CD8+ T cells, while no significant difference in FoxP3+ Treg density was observed across grades. Notably, the CD4:CD8 ratio decreased, whereas the CD8:FoxP3 ratio increased with tumor grade, indicating a shift toward a CD8-dominant immune microenvironment. Importantly, this cytotoxic predominance occurred in parallel with elevated PD-L1 expression, suggesting an immune context consistent with adaptive immune resistance rather than effective anti-tumor immunity. The IASLC grading system effectively identifies a high-risk subgroup of ALK-positive INMA characterized by aggressive tumor behavior and a dynamically regulated immune microenvironment. High-grade tumors exhibit features of immune engagement coupled with checkpoint-mediated regulation, supporting a model of adaptive immune resistance. These findings underscore the necessity of combination therapeutic strategies that simultaneously target ALK and immune checkpoint modulation in high-grade INMA.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13162233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147876138","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":"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,&nbsp;Leonie D Kandt,&nbsp;Martin Radner,&nbsp;Nora Schaumann,&nbsp;Malte Gronewold,&nbsp;Pia Hillmann,&nbsp;Henriette Christgen,&nbsp;Jens Hachenberg,&nbsp;Elna Kuehnle,&nbsp;Christian Hartmann,&nbsp;Matthias Christgen","doi":"10.1002/2056-4538.70091","DOIUrl":"10.1002/2056-4538.70091","url":null,"abstract":"<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 (<i>p</i> = 0.619), but low or absent basolateral immunoreactivity (bH-score &lt;35) was associated with premenopausal age (<i>p</i> = 0.018). Low overall FOLR1 expression (cH-score &lt;195) was also associated with premenopausal age (<i>p</i> = 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":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-23","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148091268","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 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148078348","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":"HISTAI: a valuable dataset with a valuable lesson","authors":"Katherine J Hewitt,&nbsp;Nic G Reitsam,&nbsp;Sebastian Foersch,&nbsp;Ramona Erber,&nbsp;Qinghe Zeng,&nbsp;Jakob Nikolas Kather","doi":"10.1002/2056-4538.70089","DOIUrl":"10.1002/2056-4538.70089","url":null,"abstract":"<p>The application of artificial intelligence in computational pathology depends on both robust algorithms and high-quality, clinically reliable data. Progress in this field has been limited by the scarcity of large, diverse, and well-validated whole slide image (WSI) datasets. To address this gap, HISTAI introduced an open-source resource comprising over 112,000 WSIs across multiple organ systems with associated clinical metadata. Here, we present a pathologist-led evaluation of label accuracy, metadata completeness, and dataset composition across 328 selected cases from this resource. Although HISTAI reports 47,279 cases, we identified only 44,564 unique cases after accounting for missing entries and duplicate records. Basic demographic information, including age and sex, was available for only 55% of cases. Dataset composition was uneven, with dermatopathology accounting for 47.1% of cases and gastrointestinal pathology for 24.0%; however, primary specialty was explicitly reported for only 39.6% of cases, obscuring this imbalance within the provided metadata. Notably, clinical ground truth is recorded in the Conclusion column. Concordance between the dataset's Conclusion and Diagnosis fields was observed in only 20.7% of cases, while 27.1% contained conflicting diagnoses. In a focused review of 198 cases, 30.3% were found to contain unclear or ambiguous diagnostic conclusions, including eight cases in which the diagnosis was incorrect. Assessment of molecular annotation revealed that only 18.9% of analyzed lung and colorectal cancer cases included molecular information. Furthermore, among adult-type diffuse gliomas, none of the 55 cases met current World Health Organisation Classification of Tumors of the Central Nervous System 5th Edition (WHO CNS5) diagnostic criteria, with <i>IDH</i> mutation status reported in only 15 cases. Together, these findings highlight substantial ambiguities in ground-truth labeling, incomplete molecular annotation, and limited documentation of dataset provenance and ethical oversight. While HISTAI represents a valuable open-source resource, its effective and responsible use requires careful clinical validation and close collaboration between computational researchers and pathologists.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692436","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 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148098772","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}