Pathobiology最新文献

{"title":"Performance of Large Language Models Across Diagnostic Tasks in Oral and Maxillofacial Pathology: A Systematic Review.","authors":"Sohaib Shujaat, Marryam Riaz, Hisham Albrikeet, Hongyang Ma","doi":"10.1159/pat/aehag008","DOIUrl":"https://doi.org/10.1159/pat/aehag008","url":null,"abstract":"<p><p>Introduction Large language models (LLMs) are increasingly evaluated for diagnostic applications; however, studies in oral and maxillofacial pathology (OMFP) assess materially different diagnostic tasks and outcomes. This systematic review synthesised evidence according to the specific task evaluated. Methods PubMed, Web of Science, and Cochrane Central were searched without language or date restrictions, supplemented by grey-literature screening and citation tracking. Studies evaluating defined OMFP diagnostic tasks using task-appropriate outcomes were included. Screening, data extraction, and quality assessment were independently performed by two reviewers. Owing to clinical and methodological heterogeneity, evidence was synthesised narratively by diagnostic task. Results Sixteen studies published between 2024 and 2025 were included. Seven evaluated single-diagnosis identification, six differential-diagnosis generation or ranking, five binary or multiclass classification/detection, and one structured diagnostic report generation; counts were non-mutually exclusive. Exact-diagnosis performance varied considerably and did not demonstrate consistent specialist equivalence. Differential-diagnosis studies generally reported higher Top-k inclusion than Top-1 accuracy, but these outcomes did not establish exact diagnostic correctness. Classification studies frequently reported high specificity but variable sensitivity. The single report-generation study reported item-level rather than whole-case diagnostic outcomes. Conclusion LLMs may support selected OMFP tasks, particularly differential-diagnosis generation. However, exact-diagnosis performance remains inconsistent, classification sensitivity is task-dependent, and evidence for structured report generation is limited. Current evidence does not support a single overall estimate of diagnostic performance or autonomous diagnostic use.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1"},"PeriodicalIF":1.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nectin-4 and TROP-2 in bladder cancer: biomarkers for targeted therapy.","authors":"Youwei Shi, Xue Zong, Jie Lian, Yunfan Wang","doi":"10.1159/pat/aehag006","DOIUrl":"https://doi.org/10.1159/pat/aehag006","url":null,"abstract":"<p><p>Bladder cancer is one of the most prevalent malignancies of the urinary system worldwide, with treatment strategies increasingly shifting towards precision and personalized medicine. Nectin-4 and TROP-2 are two membrane proteins highly expressed in various epithelial tumors and have emerged as critical targets for antibody-drug conjugate (ADC) therapies. This review systematically summarizes the immunohistochemical expression patterns of Nectin-4 and TROP-2 in bladder cancer tissues and explores their correlations with molecular subtypes such as luminal, basal/squamous, and neuroendocrine variants. By integrating recent clinical trial data, we analyze the clinical significance of these biomarkers in predicting therapeutic efficacy, understanding resistance mechanisms, and guiding patient selection for targeted treatments. The purpose of this review is to provide a comprehensive theoretical foundation and practical reference for advancing precision diagnostics and targeted therapeutic approaches in bladder cancer management.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1"},"PeriodicalIF":1.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visualization and Interpretation of Nuclear Features in a Deep Learning-Discriminant Analysis of Lobular Endocervical Glandular Hyperplasia with VGG16 and Linear Support Vector Machine.","authors":"Yukichi Atsumi, Fumikazu Kimura, Keiko Ishii, Yuto Saito, Masahiro Ishikawa, Takeshi Nagata","doi":"10.1159/pat/aehag009","DOIUrl":"https://doi.org/10.1159/pat/aehag009","url":null,"abstract":"<p><strong>Introduction: </strong>Lobular endocervical glandular hyperplasia (LEGH), which is considered a precursor lesion of gastric-type adenocarcinoma, exhibits subtle nuclear atypia in cytological specimens and, thus, is occasionally difficult to distinguish from normal endocervical (EC) cells. In the present study, support vector machine (SVM) and deep learning (DL) using the VGG16 model were applied to investigate whether accurate classification is achievable.</p><p><strong>Methods: </strong>Papanicolaou-stained microscopic images from 56 EC cases and 47 LEGH cases were used. Several features were extracted from each nucleus, and a classification analysis was performed using SVM and DL. Although cross-validation was performed on a case-by-case basis, accuracy was calculated at the image level because a large number of nuclear images were obtained from each case. 　Gradient-weighted Class Activation Mapping (Grad-CAM) was used to visualize attention regions in DL.</p><p><strong>Results: </strong>For the discrimination between EC and LEGH, the accuracies of SVM and DL were 84.2% and 81.2%, respectively. Accuracies between typical LEGH and atypical LEGH were 64.3% for SVM and 54.0% for DL, showing the largest difference. Grad-CAM visualized the differences in attention regions between EC and LEGH.</p><p><strong>Conclusion: </strong>The accuracy of SVM, which uses human-selected features, was slightly higher than that of DL, which automatically extracts and uses features without human intervention. This is presumably a result of humans selecting features that are more effective for discrimination. Grad-CAM showed that, in LEGH, the model evaluated the entire nuclear chromatin and focused on chromatin distribution patterns that are difficult for the human eye to discern.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1"},"PeriodicalIF":1.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into the pathophysiology of post-COVID lung disease from the perspective of histopathology.","authors":"Thomas Menter, Kirsten Mertz, Alexandar Tzankov","doi":"10.1159/pat/aehag004","DOIUrl":"https://doi.org/10.1159/pat/aehag004","url":null,"abstract":"<p><p>The COVID-19 pandemic has caused a broad range of respiratory complications. Among the spectrum of COVID-associated pulmonary conditions, severe bilateral pneumonitis that might progress to acute respiratory distress syndrome (ARDS) represents the most critical manifestation. A substantial proportion of survivors of severe COVID-19 continue to experience persistent respiratory symptoms and functional limitations. These findings are referred to as post-acute sequelae of COVID-19 (PASC). These residual post-COVID lung abnormalities are mechanistically linked to the structural changes of acute lung injury, but also to persistent systemic inflammatory signatures, and are reflected in a range of histopathological patterns, including pulmonary fibrosis, hyperinflammation, angiopathic and immunothrombotic tissue responses. This review focuses on the current knowledge of the pathogenesis and pathophysiology of post-COVID lung disease. We also schematically delineate the broad spectrum of post-COVID lung disease and explain the underlying pathomechanisms.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1"},"PeriodicalIF":1.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transforming Growth Factor-ß Signaling in Glomerular Diseases: Mechanisms of Fibrosis and Therapeutic Perspectives.","authors":"Karen Martins Mendes, Rafael Obata Trevisan, Ana Laura Carvalho Da Silva, Gláucia Eloisa Munhoz de Lion Siervo, Marlene Antônia Dos Reis, Regia Caroline Peixoto Lira, Juliana Reis Machado","doi":"10.1159/pat/aehag007","DOIUrl":"https://doi.org/10.1159/pat/aehag007","url":null,"abstract":"<p><strong>Background: </strong>Glomerular diseases are major drivers of chronic kidney disease (CKD) and end-stage renal failure worldwide. Transforming growth factor-β (TGF-β) is a central molecular regulator that integrates inflammatory, metabolic, and extracellular matrix remodeling pathways, thereby promoting renal fibrosis.</p><p><strong>Summary: </strong>This review synthesizes current evidence regarding TGF-β in glomerular diseases, emphasizing its context-dependent networks across distinct compartments of the renal microenvironment. Canonical SMAD signaling coordinates transcription of profibrotic genes, while non-canonical pathways (MAPK, PI3K/AKT, and Rho GTPases) amplify inflammatory and metabolic signaling. Rather than a uniform signaling pathway, TGF-β is shaped by disease-specific triggers, driving podocyte injury, mesangial activation, and progressive fibrotic remodeling. Despite strong experimental support, global inhibition of TGF-β has shown limited clinical success due to its pleiotropic roles in immune regulation and tissue homeostasis. Therapeutic strategies focused on selective modulation of distinct components, including SMAD3 inhibition, microRNA-based interventions, and extracellular vesicle-mediated delivery systems, show promise in attenuating profibrotic signaling while preserving physiological functions. In parallel, advances in biomarker discovery and transcriptomic profiling support biomarker-guided patient stratification and precision-based therapeutic approaches.</p><p><strong>Key messages: </strong>TGF-β signaling is a major regulator of fibrogenesis in glomerular diseases but exerts context-dependent effects. Selective targeting of pathogenic signaling nodes, rather than global inhibition, combined with biomarker-guided stratification, represents a more effective therapeutic strategy.</p><p><strong>Conclusion: </strong>TGF-β remains a compelling therapeutic target in glomerular diseases, and integrating selective pathway modulation with biomarker approaches may enable successful interventions to limit fibrosis and slow CKD progression.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1"},"PeriodicalIF":1.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HLA-I loss in germ cell tumors of the testis: potential implications for immune evasion, preservation of the stem cell phenotype, and reprogramming.","authors":"Marco Grillini, Agnese Orsatti, Francesca Ambrosi, Antonio De Leo, Francesco Vasuri, Federico Mineo Bianchi, Veronica Mollica, Francesco Massari, Joao Lobo, Nuno Tiago Tavares, Fernanda Fernandes-Pontes, Andres M Acosta, Maurizio Colecchia, Ezra Baraban, Michelangelo Fiorentino, Costantino Ricci","doi":"10.1159/pat/aehag003","DOIUrl":"https://doi.org/10.1159/pat/aehag003","url":null,"abstract":"<p><strong>Introduction: </strong>Previous studies have analyzed the \"reprogramming\" of germ cell tumors of the testis (GCTT), which is a complex genetic/epigenetic process regulated by tumor microenvironment (TME) and resulting in the preservation of stem cell features and/or the differentiation of GCTT. Human leukocyte antigens class I (HLA-I) is a key regulator of the interactions between tumor cells and TME, but few studies have studied its expression in GCTT, germ cell neoplasia in situ (GCNIS), and \"normal\" adjacent testis (AT).</p><p><strong>Methods: </strong>We tested 102, 41 and 26 GCTT components, GCNIS, and AT, respectively. HLA-I expression was scored (intact/retained, sub-clonal loss, and complete loss), dichotomized, and compared between different subgroups by adopting Fisher's exact test.</p><p><strong>Results: </strong>We found that HLA-I loss was more frequent in seminoma (S) and embryonal carcinoma (EC) rather than in the other non-seminomatous GCTT (NS-GCTT) (p<0.001 and p: 0.002). HLA-I was positive in all GCNIS (41/41, 100%), thus being statistically significant compared to both GCTT (p<0.001) and AT (p<0.001). HLA-I loss was found in all AT (26/26, 100%), with a characteristic \"patterned\" expression (loss in spermatids, spermatozoa, and spermatogonia; expressed by spermatocytes).</p><p><strong>Conclusions: </strong>\"HLA-I loss\" varies during the GCTT reprogramming, thus supporting its role in the crosstalk between TME and GCTT, which is crucial for the maintenance of stem cell features (S and EC) and specific differentiation programs (other NS-GCTT). Future studies are needed to explore its role in GCNIS and AT.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1"},"PeriodicalIF":1.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Proof-of-Concept Study of Digital Spatial Distance Analysis in Ovarian Mature and Immature Teratomas.","authors":"Keisuke Kanetaka, Kei Koyama, Tomonori Tsuruhashi, Hikaru Tsukita, Takahiro Ishinari, Ayana Takahashi, Ken Miyabe, Makoto Yoshida, Yukitsugu Kudo-Asabe, Hiroshi Nanjo, Kenichi Makino, Tae Sugawara, Takeo Hirakawa, Enami Kaneko, Masato Waga, Yukihiro Terada, Akiteru Goto","doi":"10.1159/pat/aehag001","DOIUrl":"10.1159/pat/aehag001","url":null,"abstract":"<p><strong>Introduction: </strong>Mature (MT) and immature teratomas (ITs) contain diverse histological components; however, their tissue-level spatial organization remains poorly understood. This proof-of-concept study aimed to develop a reproducible digital pathology workflow for quantifying the spatial distances among histological components of ovarian teratomas.</p><p><strong>Methods: </strong>Four representative mature teratoma sections and three ITs with neural elements were analyzed. Whole-slide images of hematoxylin and eosin-stained sections were manually annotated, and each morphologically recognizable component was represented by a centroid using a Python-based image analysis method. Pairwise centroid-based distances were calculated using brute-force and nearest-distance approaches, followed by an exploratory statistical analysis.</p><p><strong>Results: </strong>Anatomically related tissue pairs, including bronchial epithelium-bronchial gland and epidermis-hair follicle, showed relatively short centroid-based distances, suggesting that the workflow can capture the expected tissue-level architectural relationships. Additional associations, such as bronchial gland-bone proximity, were also observed but should be interpreted as hypothesis-generating findings. No consistent spatial proximity was observed between the immature and mature components.</p><p><strong>Conclusion: </strong>These findings support the technical feasibility of the proposed workflow for the exploratory tissue-level spatial analysis of teratomas, while emphasizing that spatial associations do not directly demonstrate biological interactions, developmental induction, or lineage relationships.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1"},"PeriodicalIF":1.7,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Squamous Cells in the Thyroid Gland's Cytopathology and Histopathology: Institutional Experience.","authors":"Iiris Maria Harjunpää, Eliisa Eveliina Viljanen, David Kalfert, Ivana Kholová","doi":"10.1159/pat/aehag002","DOIUrl":"10.1159/pat/aehag002","url":null,"abstract":"<p><p>Introduction Squamous cells are a rare finding in the thyroid gland and have been reported in a wide range of entities, from benign cysts to carcinomas. This study presents the diagnostic outcomes and potential pitfalls associated with squamous cell lesions in the thyroid gland, based on the experience of a tertiary centre's pathology laboratory. The main focus of the present study was on morphology, cytohistological correlation, immunohistochemistry and diagnostic pitfalls. Methods A pathology laboratory's information system was searched for squamous cell findings in the thyroid gland. Cytological samples were classified according to the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), and histological specimens were categorised according to the World Health Organization (WHO) classification. Available microscopy slides were re-examined, and selected immunohistochemical and morphological features were documented. Results Our series included 42 thyroid gland specimens containing squamous cells, comprising 22 cytological samples and 20 histological samples. The most common diagnosis by the Bethesda Category for Thyroid Cytopathology (TBSRTC) was malignant (VI, 50%). According to histologies, most cases were malignant (n = 10, 62.5%), with anaplastic thyroid carcinoma (ATC) being the most frequent diagnosis (n = 5, 31.3%). There was one discordant case in which cytology suggested a benign lesion, whereas histology revealed an ATC. Morphologically, squamous cells in TBSRTC categories V and VI were atypical, and inflammatory infiltrates were more profound. CK5/6 and p40 were positive in all tested squamous cells. Conclusion The presence of squamous cells in thyroid samples can make diagnosis challenging, highlighting the need to correlate findings with clinical information. In this study, disagreements regarding malignancy between cytology and histology occurred in only one of nine cases. Only diagnostic discordance occurred in two out of nine cases.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1"},"PeriodicalIF":1.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activated Cancer-Associated Fibroblasts Are Associated with Immunosuppression and Poor Prognosis in Clear Cell Renal Cell Carcinoma.","authors":"Soohwan Choi, Myungsun Shim, Kyueng-Whan Min, Yung-Kyun Noh, Hyung Suk Kim, Kyu Shik Kim, Un Suk Jung, Kyung Suk Lee, Mi Jung Kwon","doi":"10.1159/000553452","DOIUrl":"10.1159/000553452","url":null,"abstract":"<p><strong>Introduction: </strong>Clear cell renal cell carcinoma (ccRCC) exhibits substantial heterogeneity within its tumor microenvironment, contributing to variable clinical outcomes. The prognostic significance and molecular characteristics of cancer-associated fibroblasts in ccRCC remain poorly defined.</p><p><strong>Methods: </strong>We analyzed 736 ccRCC cases (203 institutional and 533 TCGA) to identify histologically distinct activated cancer-associated fibroblasts (aCAFs; oval to mildly elongated immature fibroblasts occupying >5% of stroma) on H&E-stained slides. Clinicopathological correlations, immunohistochemical immune profiling, transcriptomic analyses, and machine learning-based survival modelling were performed; for the latter, 17 neoadjuvant-treated cases were excluded from the TCGA cohort, yielding an analytic cohort of 516 cases.</p><p><strong>Results: </strong>aCAFs were identified in 12.3% and 12.9% of institutional and TCGA cohorts, respectively, and were significantly associated with advanced tumor stage, higher histologic grade, sarcomatoid features, and poor disease-specific survival, remaining an independent prognostic factor on multivariate analysis. aCAF-positive tumors exhibited reduced tumor-infiltrating lymphocytes and CD4+ T-cell infiltration, enhanced TGF-β signaling, and molecular enrichment in FGFR2 and complement regulation pathways. In machine learning-based survival models, aCAFs ranked among the top five prognostic predictors, and their inclusion improved predictive accuracy with DSS AUC of 0.874 versus 0.858. In silico drug screening identified ponatinib and HG6-64-1 as candidate therapeutic agents for tumors with high fibroblast activation protein-α expression.</p><p><strong>Conclusion: </strong>Morphologically defined aCAFs represent a histologically recognizable and clinically meaningful stromal component associated with immunosuppression and adverse prognosis in ccRCC, with potential utility for routine diagnostic application and therapeutic targeting.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-14"},"PeriodicalIF":1.7,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted Next-Generation Sequencing-Based Mutational Signature Analysis in Hypermutated Gliomas: A Case-Centered Feasibility Assessment.","authors":"Seon Ung Kim, Youn Soo Lee, Sin-Soo Jeun, Jae-Sung Park, Donghyuk Lee, Jun Kang","doi":"10.1159/000553407","DOIUrl":"10.1159/000553407","url":null,"abstract":"<p><strong>Introduction: </strong>Gliomas generally display a low tumor mutational burden (TMB) and an immunosuppressive microenvironment, both of which restrict the effectiveness of immune checkpoint inhibitors. However, certain gliomas acquire a high TMB, which may arise either due to temozolomide (TMZ) therapy or mismatch repair deficiency. Mutational signature analysis identifies specific somatic mutation patterns, providing insight into underlying mutational mechanisms. This study provides a case-centered feasibility assessment of mutational signature refitting from a clinically implemented targeted next-generation sequencing (NGS) panel in two hypermutated gliomas identified within a real-world glioma testing cohort.</p><p><strong>Methods: </strong>Twenty-eight gliomas tested using the Oncomine Comprehensive Assay Plus NGS panel in routine clinical practice were retrospectively reviewed. Panel-derived TMB was used for coarse stratification and to identify hypermutated tumors for detailed mutational signature interpretation. Mutational signature refitting was performed using Signature Analyzer for Targeted Sequencing.</p><p><strong>Results: </strong>Two gliomas exhibited elevated panel-derived TMB estimates: one after TMZ therapy and another in association with MSH2 deficiency. The remaining 26 non-hypermutated tumors had sparse mutation counts, limiting reliable signature interpretation. COSMIC single-base substitution signature 11 (SBS11) was predominant in the TMZ-treated hypermutated glioma, whereas the MSH2-deficient glioma demonstrated increased SBS1 and SBS26.</p><p><strong>Conclusion: </strong>This real-world, case-centered study suggests that targeted-panel mutational signature refitting may provide complementary molecular context in selected hypermutated gliomas. The observed patterns were concordant with prior TMZ exposure or mismatch repair deficiency. However, in non-hypermutated tumors, sparse mutation counts limited reliable signature interpretation, and the clinical impact of this approach remains to be established.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-10"},"PeriodicalIF":1.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405316","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}