Brain Pathology最新文献

{"title":"A 38-year-old female with seizures and a cortico-subcortical mass.","authors":"Marjolein Billen, Annemerel Van Wylick, Anne-Marie Vanbinst, Hendrik Everaert, Freya Vaeyens, Johnny Duerinck, Bart Neyns, Stefanie Brock","doi":"10.1111/bpa.70150","DOIUrl":"10.1111/bpa.70150","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70150"},"PeriodicalIF":5.0,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149011858","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":"Neuropathology of a patient with Parkinson's disease and biallelic expansion in RFC1.","authors":"Jussi Sipilä, Tuomas Rauramaa, Laura Kytövuori, Kari Majamaa","doi":"10.1111/bpa.70152","DOIUrl":"10.1111/bpa.70152","url":null,"abstract":"<p><p>This is the first report of neuropathology in biallelic RFC1 expansion-associated Parkinson's disease (PD). It shows a synucleinopathy of intraneuronal Lewy bodies consistent with the clinical PD diagnosis while neuropathological CANVAS (Cerebellar Ataxia with Neuropathy and bilateral Vestibular Areflexia) features were absent.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70152"},"PeriodicalIF":5.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988258","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":"Enhancement of the leptomeninges in a young man.","authors":"Jayden Ray, Mohammad Alberawi, Andrew Bauer, Kar-Ming Fung, Erika Santos Horta, Lorraina J Robinson","doi":"10.1111/bpa.70145","DOIUrl":"10.1111/bpa.70145","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70145"},"PeriodicalIF":5.0,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13581456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982458","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":"Circumscribed Meningeal Melanocytic Neoplasms: CNS WHO Grade, Molecular Profile, and Clinical Outcomes.","authors":"Yi Zhu, Nishika Karbhari, Timothy J Kaufmann, Aditya Raghunathan, Cristiane M Ida, Cinthya J Zepeda-Mendoza, Ian J Dryden, Shahriar Salamat, Chathu Atherton, Sarah M Jenkins, Svetomir N Markovic, Ugur T Sener, Caterina Giannini","doi":"10.1111/bpa.70147","DOIUrl":"10.1111/bpa.70147","url":null,"abstract":"<p><p>Circumscribed meningeal melanocytic neoplasms (CMMNs) represent a spectrum of rare central nervous system (CNS) tumors. Knowledge of their clinical behavior and molecular correlates remains limited. In this single-institution retrospective study, we analyzed 31 patients (14 male, 17 female; median age, 59 years) diagnosed with CMMN between 2004 and 2025. In this patient cohort, based on the current World Health Organization Central Nervous System Tumor Classification (WHO CNS5) criteria, the majority of cases (18, 58.1%) fell into the intermediate-grade melanocytic tumor (IMT) category based on histology, with either increased mitotic activity, CNS invasion, or both; 7 (22.6%) were melanocytomas, 5 (16.1%) melanomas, and 1 (3.2%) indeterminate case because of limited tissue. By next-generation sequencing, mutations were identified in GNAQ/GNA11 in 21/24 cases, BAP1 in 5/23 (2 IMT, 3 melanoma), EIF1AX in 9/21 (1 melanocytoma, 8 IMT), and SF3B1 in 3/23 (2 IMT, 1 melanoma). Primary sites were spinal (20), posterior fossa (6), and supratentorial (5). During follow-up, progression was observed in 5/6 melanocytomas, 9/13 IMTs, and 4/5 melanomas, suggesting a high frequency of progression across all groups. Two-year progression-free survival was 83.3% (95% confidence interval [CI], 53.5%-100.0%) for melanocytoma, 55.9% (95% CI, 26.7%-85.2%) for IMT, and 25.0% (95% CI, 0.0%-67.4%) for melanoma. Five-year overall survival (OS) was 80.0% (95% CI, 44.9%-100.0%) for melanocytoma, 65.3% (95% CI, 37.0%-93.6%) for IMT, and 0.0% for melanoma. OS was significantly worse in melanoma compared with melanocytoma (p = 0.002). BAP1 mutation correlated with worse OS (hazard ratio 8.73, p = 0.006). Upfront maximal safe resection appeared to be associated with improved outcomes in selected patients, whereas radiotherapy and systemic therapy did not demonstrate clear additional benefit in this cohort. In summary, our study shows that all CMMNs, irrespective of grade, have a high propensity to recur and melanoma histology and BAP1 mutation are associated with significantly worse OS.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70147"},"PeriodicalIF":5.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966468","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":"Dysregulated TIE-2 expression in Alzheimer's disease: Further considerations on regional specificity and shedding evidence.","authors":"Shi-Qi Zhang, Meichen Liu","doi":"10.1111/bpa.70151","DOIUrl":"10.1111/bpa.70151","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70151"},"PeriodicalIF":5.0,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148962996","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":"PTEN homozygous deletion is a negative prognostic factor in tumor treating fields-treated glioblastoma, IDH wildtype patients.","authors":"Jakob Nückles, Claudius Jelgersma, Christin Siewert, Brendan Osberg, Simone Schmid, Arend Koch, Eilís Perez, Daniel Teichmann, Martin Misch, Anna-Gila Karbe, Susanne Ukrow, Patrick N Harter, Ruth M Stassart, Peter Vajkoczy, Julia Onken, David Capper","doi":"10.1111/bpa.70143","DOIUrl":"10.1111/bpa.70143","url":null,"abstract":"<p><p>Tumor treating fields (TTFields) are a treatment for glioblastoma, isocitrate dehydrogenase wildtype (GBM, IDH wt) that improves survival, but no validated biomarkers exist to identify patients likely to benefit. This study aims to identify molecular biomarkers guiding clinical decisions on TTFields initiation. Eighty gliomas treated with surgery, radiochemotherapy, and TTFields were reassessed using DNA methylation profiling and TSO500 DNA/RNA panel sequencing, identifying 64 highly characteristic GBM, IDH wt with comprehensive molecular data. Alterations present in ≥5 cases were analyzed for association with survival using Kaplan-Meier and Cox models. Two TTFields-naïve GBM, IDH wt cohorts (n = 175) served as controls. For 18 cases, post-treatment tissue from a second surgery was profiled. Twenty-four alterations occurred in ≥5 patients. Univariate analyses showed KPS and MGMT promoter methylation as protective, while EGFR amplification, CDKN2A/B loss, and homozygous PTEN deletion were linked to worse survival with TTFields. Multivariate analysis confirmed KPS and MGMT as protective and homozygous PTEN deletion as a risk factor (median OS 368 vs. 603 days; HR 3.86, p = 0.0049). In TTFields-naïve cohorts, homozygous PTEN deletion was not associated with outcome, and frequencies were comparable (controls 7%, TTFields 11%). Post-TTFields GBM, IDH wt did not acquire hypermutation or other recurrent molecular alterations. Alongside the established factors MGMT and KPS, PTEN homozygous deletion was associated with worse survival in GBM, IDH wt patients treated with TTFields. Homozygous PTEN deletion may be associated with reduced benefit from TTFields and should be further investigated as a predictive biomarker for TTFields treatment.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70143"},"PeriodicalIF":5.0,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13561735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929005","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 profiling of pediatric medulloblastoma in Kazakhstan: Genomic alterations, subgroup distribution, and survival.","authors":"Aidos Bolatov, Askhat Zhakupov, Aizhan Abdikadirova, Malika Sapargaliyeva, Bakytkali Ibraimov, Zhanat Zhalimbetova, Gabit Ólenbay, Berik Zhetpisbayev, Xingzhi Xu, Mirgul Bayanova","doi":"10.1111/bpa.70144","DOIUrl":"10.1111/bpa.70144","url":null,"abstract":"<p><p>Medulloblastoma is the most common malignant pediatric brain tumor and comprises biologically distinct molecular subgroups with different clinicopathologic and prognostic characteristics. Molecular data from Kazakhstan and other underrepresented regions remain limited, and practical approaches for molecular subgroup assignment using formalin-fixed, paraffin-embedded (FFPE) material are needed in settings where advanced molecular classification is not routinely available. We retrospectively analyzed 40 pediatric medulloblastomas diagnosed between 2015 and 2024 at the Corporate Fund \"University Medical Center,\" Kazakhstan. Archived FFPE tumor material underwent histologic review, immunohistochemical evaluation (β-catenin, YAP1, and GAB1), and whole-exome sequencing. Tumors were assigned to WNT, SHH, or non-WNT/non-SHH categories using a combined morphologic, immunophenotypic, and genomic framework, and clinicopathologic variables and overall survival were evaluated across subgroups. WNT medulloblastomas (n = 7, 17.5%) showed the most canonical profile, characterized by classic histology, uniform β-catenin nuclear positivity, recurrent CTNNB1/APC alterations, and frequent chromosome 6 loss. SHH medulloblastomas (n = 10, 25.0%) were enriched for desmoplastic/nodular morphology, frequent YAP1/GAB1 expression, pathogenic PTCH1/SUFU alterations, and additional events involving TP53, TERT, and focal amplifications in a subset. Non-WNT/non-SHH medulloblastomas (n = 23, 57.5%) showed the greatest genomic heterogeneity, including frequent i17q and broader structural complexity. Clinically, WNT tumors occurred predominantly in older children and had the most favorable survival, whereas non-WNT/non-SHH tumors were the only subgroup associated with metastatic disease at presentation and showed the poorest long-term survival. Overall, pediatric medulloblastoma in this cohort demonstrated subgroup-specific patterns consistent with established biology. The integration of pathology, immunohistochemistry, and sequencing enabled clinically meaningful molecular stratification. These findings expand evidence from an underrepresented setting and support pragmatic, resource-adapted profiling in routine practice.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70144"},"PeriodicalIF":5.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905028","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":"Clinical evaluation of the CrossNN DNA methylation classifier for central nervous system tumors.","authors":"Jonas Dahnoun, Léon C van Kempen, Senada Koljenović, Ken Op de Beeck, Tomas Menovsky, Bart Feyen, Melek Ahmed, Anne Sieben, Karen Zwaenepoel","doi":"10.1111/bpa.70137","DOIUrl":"10.1111/bpa.70137","url":null,"abstract":"<p><p>DNA methylation profiling is an integral diagnostic tool in the classification of central nervous system (CNS) tumors. While the Heidelberg CNS Tumor Methylation Classifier is widely used to support CNS tumor diagnostics, new classifiers such as CrossNN are emerging. However, their clinical performance and added value within routine diagnostic workflows remain insufficiently explored. In this study, we evaluated the diagnostic performance of the CrossNN classifier in a real-world CNS tumor cohort and compared it with the established Heidelberg classifier to assess its potential as both a non-inferior alternative and a complementary tool to improve diagnostic accuracy. A retrospective cohort of CNS tumors profiled using Illumina Human Methylation 930k EPIC v2 BeadChip arrays was analyzed. Classifier outputs were compared with integrated WHO CNS5 (2021) diagnoses. In addition, CrossNN and Heidelberg outputs were harmonized to WHO CNS5 (2021) tumor type levels and evaluated both individually and within sequential and parallel diagnostic workflows. The proposed workflows were subsequently assessed in an independent prospective validation cohort. Among 205 samples, CrossNN correctly classified 88.8% of cases and demonstrated 86.8% concordance with the Heidelberg classifier. CrossNN demonstrated non-inferior classification performance compared with the Heidelberg classifier. Combining both classifiers increased the number of clinically informative and correct classifications by nearly 10%. This finding was confirmed in an independent validation cohort of 41 samples. In conclusion, these results demonstrate the complementary strength of the CrossNN and Heidelberg classifiers as a dual-classifier strategy to improve diagnostic confidence and accuracy in routine CNS tumor diagnostics.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70137"},"PeriodicalIF":5.0,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13537830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879119","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":"Immunohistochemistry as a tool for identifying PDGFRA amplification in central nervous system tumors.","authors":"Arnault Tauziède-Espariat, Guilhem Amargos, Farah Sassi, Lauren Hasty, Alice Métais, Pascale Varlet","doi":"10.1111/bpa.70142","DOIUrl":"10.1111/bpa.70142","url":null,"abstract":"<p><p>PDGFRA gene amplification is now recognized as a diagnostically and prognostically relevant molecular alteration in central nervous system tumors. Herein, we demonstrated that PDGFRA immunohistochemistry is a highly specific and sensitive biomarker for identifying PDGFRA amplification and should be part of the neuropathologist's routine panel of antibodies.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70142"},"PeriodicalIF":5.0,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872746","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":"Complement receptor C3aR marks heterogeneous tumor-associated macrophage states associated with improved survival in IDH-wildtype glioblastoma.","authors":"Marion Imara, Yosra Bedoui, Théotime Pignolet, Sebastien Freppel, Camille Brochard, Auguste Delattre, David Cappellen, Luc Bauchet, Mohamed Khettab, Franck Ah-Pine","doi":"10.1111/bpa.70141","DOIUrl":"10.1111/bpa.70141","url":null,"abstract":"<p><p>Glioblastomas (GBM), IDH-wildtype, are highly aggressive brain tumors with poor prognosis and inter-individual variability despite established prognostic factors such as age, performance status, and MGMT promoter (MGMTp) methylation. Increasing evidence highlights the role of the tumor microenvironment (TME) in GBM progression. The complement system, a key component of innate immunity, can influence tumor growth and immune regulation through the generation of the anaphylatoxin C3a and the activation of its receptor, C3aR. While C3a/C3aR signaling has been associated with various outcomes in several malignancies, its prognostic relevance in GBM remains poorly defined. This study investigated the expression of C3aR in human IDH-wildtype GBM and its association with clinicopathological features and overall survival. We retrospectively analyzed a cohort of 114 patients with IDH-wildtype GBM. C3aR expression was assessed by immunohistochemistry and quantified using digital image analysis. C3aR expression was analyzed as a categorical variable using an outcome-derived cutpoint (C3aR-high and C3aR-low) for exploratory purposes. Associations with clinical variables, including MGMTp methylation status, were evaluated. C3aR expression showed marked inter-tumoral heterogeneity and was enriched among MGMTp-methylated tumors (p = 0.004). Patients with C3aR-high tumors exhibited improved overall survival (log-rank p = 0.033). In a multivariable Cox regression model including age, performance status, surgery type, and MGMTp methylation status, high C3aR expression remained independently associated with improved overall survival (HR 0.50, 95% CI 0.29-0.87, p = 0.014). Tissue-based and single-cell analyses supported the association of C3aR with the myeloid/macrophage compartment and heterogeneous macrophage phenotypes. These findings support a relationship between C3aR expression and the heterogeneous macrophage landscape of IDH-wildtype GBM, while the survival association remains exploratory and requires independent validation.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70141"},"PeriodicalIF":5.0,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863339","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}