Brain Pathology最新文献

{"title":"Data-driven thresholds for standardized classification of severe Alzheimer's disease neuropathology using digital neuropathology","authors":"Ryan K. Shahidehpour,&nbsp;Allison M. Neltner,&nbsp;Mitchell A. Klusty,&nbsp;Cole Corbett,&nbsp;Angelique D. Gonzalez,&nbsp;David A. Gutman,&nbsp;David W. Fardo,&nbsp;Adam D. Bachstetter,&nbsp;Cody Bumgardner,&nbsp;Margaret E. Flanagan,&nbsp;Peter T. Nelson","doi":"10.1111/bpa.70102","DOIUrl":"10.1111/bpa.70102","url":null,"abstract":"<p>Alzheimer's disease neuropathological changes (ADNC)—operationalized with semi-quantitative parameters—represent the consensus-based gold standard for diagnostic evaluation of disease severity. Although useful, ADNC diagnostic frameworks have limitations, particularly in advanced disease stages where pathological severity varies widely within a given diagnostic category. Further, some individuals lacking cognitive impairment are inappropriately categorized as having severe ADNC. In this study, quantitative pathology metrics and alternative tissue sampling schemes were integrated with data about premortem cognitive status, in order to derive clinically informed neuropathologic diagnostic thresholds. Specific goals of the current study were to generate data-driven, standardized diagnostic cut-points, with the most severe stages of ADNC having consistent implications: Braak neurofibrillary tangle (NFT) stage V cases being always impaired (MCI or demented) and Braak NFT stage VI cases being always demented. Utilizing whole-slide imaging and AI-based image analysis, object-based (NFT counts) and pixel-based (phosphorylated tau [pTau] burden) quantifications were compared across neocortical regions in three subsamples of cases from the University of Kentucky ADRC autopsy cohort (<i>n</i> = 329, all with clinical evaluations within 2 years of death). We also compared between HALO- and Aperio-based platform results, and between AT8 and PHF-1 pTau antibodies. Applying refined thresholds enabled reclassification of cases previously misaligned with their digitally determined appropriate status: 17% of cases were thus reclassified. The use of commercially available software, standardized classifier architectures, and interoperable analysis pipelines facilitated scalable and reproducible digital quantification. Cross-institutional validation at University of Texas San Antonio, with the same algorithms applied in both research centers, confirmed near-perfect agreement of pathology counts, underscoring shareability and the feasibility of harmonized digital workflows for collaborative research and diagnostic purposes. These findings support the integration of quantitative digital pathology into standard neuropathological protocols and provide a scalable model for future multi-site studies. Enabling comparisons of analytical platforms, pTau antibodies, and anatomical sampling strategies, an updated workflow demonstrated high reproducibility and consistent clinical-pathological correlations.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762952","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":"11-year-old girl presenting with blurred vision and progressive right arm weakness","authors":"Trung Toan Tran,&nbsp;Thi My Hanh Luong,&nbsp;Bérengère Dadone-Montaudié,&nbsp;Hong Nhung Ta,&nbsp;Thai Hoc Nguyen,&nbsp;Fanny Burel-Vandenbos,&nbsp;Gia Du Pham","doi":"10.1111/bpa.70097","DOIUrl":"10.1111/bpa.70097","url":null,"abstract":"&lt;p&gt;An 11-year-old girl, with no significant medical history, presented to the Vietnam National Cancer Hospital with blurred vision in both eyes and progressive weakness in the right arm over a two-week period. Brain magnetic resonance imaging (MRI) revealed a well-defined, solid and cystic lesion in the left parietal hemisphere, measuring 53 × 57 mm, causing a significant mass effect (Figure 1). Whole-body imaging showed no evidence of lesions elsewhere. Intraoperatively, the tumor was entirely intraparenchymal, with its base infiltrating the motor white matter. The solid portion was resected, and the cystic part preserved due to adherence to critical tracts.&lt;/p&gt;&lt;p&gt;Histopathology showed a proliferation of fibroblast- and myofibroblast-like cells with heterogeneous cellularity (Figure 2A,B), vesicular nuclei, small nucleoli, and pale eosinophilic cytoplasm (Box 1). Scattered ganglion-like and pleomorphic cells were observed (Figure 2C,D), while mitoses were rare. The stroma contained macrophages, lymphocytes, and plasma cells, with focal myxoid changes. Diagnoses of glioma, meningioma, and solitary fibrous tumor were ruled out, based on the negativity of GFAP, OLIG2, EMA, PR, and STAT6. ATRX and INI1 were maintained. CD68 was positive, but Langerin, CD1a, and S100 were negative, excluding histiocytosis. The only other positive immunostainings were CD99, ALK1, and actin (Figure 2E,F), which rather pointed toward the group of mesenchymal tumors. Proliferation index KI67 was 5%. RNA sequencing identified a TMP4::ALK fusion. No additional mutations were detected by DNA sequencing (Ion AmpliSeq Cancer Hotspot Panel, Life Technologies).&lt;/p&gt;&lt;p&gt;Inflammatory myofibroblastic tumor.&lt;/p&gt;&lt;p&gt;IMT, a spindle cell neoplasm of intermediate malignancy, long considered an inflammatory pseudotumor (IPT), has been recognized and described as a distinct entity in the 2020 WHO classification of soft tissue tumors [&lt;span&gt;1&lt;/span&gt;]. Intracranial IMT is extremely rare, accounting for 21 out of 25 reported cases in the literature of central nervous system (CNS) IMT/IPT in patients aged 0–24 years [&lt;span&gt;2&lt;/span&gt;]. Due to its rarity in the CNS, IMT is not included in the 2021 WHO Classification of CNS Tumors, which instead lists new entities with overlapping histological features [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Clinical and MRI features of IMTs are nonspecific, and diagnosis relies on histopathology and immunohistochemistry. Histologically, IMTs show spindle cell proliferation with dense lymphoplasmacytic infiltrate and three main patterns that may coexist: (1) nodular fasciitis-like, (2) fibromatosis/fibrohistiocytic, and (3) desmoid-like. Necrosis, fascicular or herringbone architecture, multinucleation, pleomorphism, ganglion-like cells, and atypical mitoses indicate more aggressive variants [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Spindle cells variably express myoid markers such as smooth muscle actin and desmin, but are typically negative for glial markers, S100, CD117, and DOG1. ALK1 expressio","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509696","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":"Hippocampal inflammasome enrichment in intermediate Alzheimer's disease: Strong spatial findings, but clearer stage and mechanistic definition are needed","authors":"Chenhong Zeng,&nbsp;Baodong Wang,&nbsp;Yehua Bao","doi":"10.1111/bpa.70103","DOIUrl":"10.1111/bpa.70103","url":null,"abstract":"&lt;p&gt;We read with great interest the study by de Rivero Vaccari et al. on inflammasome signaling in selective brain regions during the intermediate stage of Alzheimer's disease (AD) [&lt;span&gt;1&lt;/span&gt;]. The authors compare the hippocampus, temporal cortex, and frontal cortex, and combine gene profiling with protein and imaging data. Their central message is clear and important: inflammasome-related signals are strongest in the hippocampus, are linked to neuritic plaque-rich areas, with sex-stratified analyses suggesting a possibly stronger signal in some female subgroups. This work adds useful detail to the growing literature on innate immune activity in AD.&lt;/p&gt;&lt;p&gt;The study has several strong points. The regional design is a major advantage, because AD pathology does not spread evenly across the brain [&lt;span&gt;2&lt;/span&gt;]. The finding that the hippocampus shows the largest rise in inflammasome-related genes and proteins fits well with the known early damage of this region. The use of a broad marker set, including ASC, NLRP1, NLRP3, AIM2, caspase-1, and GSDMD, also gives the paper a wider scope than many earlier reports. In addition, the use of pTau217 is timely and adds clinical value, since this marker is gaining attention in AD diagnosis [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;At the same time, several issues deserve closer attention. First, the definition of the intermediate AD group remains broad. The study combines cases across Braak stages III to V [&lt;span&gt;1&lt;/span&gt;]. This range likely includes brains at different points of disease spread. Because the main claim of the paper is regional selectivity, stage mixing may weaken the precision of the conclusion. A case at Braak III is not equal to a case near Braak V in terms of cortical tau burden, plaque load, and inflammatory state [&lt;span&gt;4-6&lt;/span&gt;]. A stage-stratified analysis, even if only exploratory, would help show whether the hippocampal signal is stable across the whole intermediate range or driven mainly by later cases within that group.&lt;/p&gt;&lt;p&gt;Second, the link between inflammasome activation and pyroptotic death should be stated more carefully. The increase in GSDMD staining is interesting, but it does not by itself prove active pyroptosis [&lt;span&gt;7&lt;/span&gt;]. Stronger support would require evidence of the cleaved GSDMD fragment, active caspase-1, and mature IL-1 family cytokines. Without these data, the findings support a pyroptosis-related pattern, but not a firm conclusion that pyroptotic cell death is taking place. This point becomes more important because the paper moves from region-based gene data to a stronger mechanistic claim about cell death.&lt;/p&gt;&lt;p&gt;A related issue is regional matching across assays. The transcriptomic work focuses on the hippocampal CA1 region, whereas the GSDMD imaging analysis is taken from CA2 [&lt;span&gt;1&lt;/span&gt;]. Since hippocampal subfields differ in anatomical and molecular organization, and also show differential vulnerability to tau pathology, this shift may affect interpretation [&lt;sp","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148197309","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":"Human brain matters: Navigating the neuropathology of COVID-19","authors":"Juliana M. Nieuwland,&nbsp;Angelica Scaramuzza,&nbsp;Marianna Bugiani,&nbsp;Wilma D. J. van de Berg,&nbsp;Jinte Middeldorp","doi":"10.1111/bpa.70101","DOIUrl":"10.1111/bpa.70101","url":null,"abstract":"<p>Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of deaths worldwide. Although the incidence of severe acute cases has declined, the prevalence of long COVID, also known as post-acute sequelae of COVID-19 (PASC), is rising. The pathological mechanisms underlying severe COVID-19, along with the relationship to neurological disorders and potential risk for neurodegeneration, remain poorly understood. The aim of this narrative review is to summarize neuropathological features described in postmortem human COVID-19 brains (<i>n</i> = 352). Furthermore, analysis of biofluids and neuroimaging from PASC patients underline long-term changes in the proteome and CNS response following the infection. Postmortem brain studies from severe COVID-19 patients highlight disruption of the fluid-brain barriers and vascular dysregulation defined by endothelial inflammation and disruption, hemorrhages, and hypoxic–ischemic damage. Neuroinflammation, including astrogliosis, microglia nodules and infiltration of adaptive immune cells, has been reported in the olfactory bulb, medulla oblongata, midbrain and cerebellum. Neuronal damage was demonstrated in the hippocampus, midbrain and cerebellum in severe COVID-19 and protein aggregation was observed in the midbrain and entorhinal cortex. Neuropathological burden and elevated blood and/or cerebrospinal fluid (CSF) levels of proinflammatory cytokines (e.g. IL-6) and neuro-axonal proteins (e.g. NfL) correlated with severity of anosmia, memory deficits, and cerebellar ataxia. Elderly patients and/or patients with underlying neurological diseases were more susceptible and had worsened symptoms. Potential disease mechanisms underlying neurological symptoms observed in severe COVID-19 are vascular and fluid-brain barrier abnormalities, chronic neuroinflammation, persistent axonal damage and protein aggregation. In PASC patients, an altered biofluid proteome with increased neuronal proteins and pro-inflammatory cytokines was observed. The pathological burden in affected brain regions may contribute to manifestations such as anosmia, memory deficits, and cerebellar ataxia.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762993","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":"Brain viral reservoir seeding and neurological metabolic dysregulation in early-life immunodeficiency virus infection","authors":"Li Ma,&nbsp;Robert Blair,&nbsp;Yao-Zhong Liu,&nbsp;Xiaolei Wang,&nbsp;Eunice Vincent,&nbsp;Christopher Yu,&nbsp;Lara A. Doyle-Meyers,&nbsp;Cissy Zhang,&nbsp;Ahmad Saied,&nbsp;Anne Le,&nbsp;Ronald S. Veazey,&nbsp;Qigui Yu,&nbsp;Huanbin Xu","doi":"10.1111/bpa.70104","DOIUrl":"10.1111/bpa.70104","url":null,"abstract":"<p>While viral reservoirs establish rapidly in the peripheral and lymphoid tissues in HIV-exposed and infected infants, the timing and consequences of viral seeding in the developing brain remain unclear. Using a neonatal rhesus macaque SIV model, we tracked early brain-associated viral DNA/RNA, neuropathology, and cerebrospinal fluid (CSF) metabolism, and evaluated the impact of early antiretroviral therapy (ART). CSF viral RNA was detectable by 2 days post infection (dpi), mirroring plasma viral load kinetics. In contrast, brain tissue SIV DNA and RNA remained largely undetectable through the first 3 days of infection. Despite this early viral dissemination, we observed no significant neuropathological lesions or CSF proinflammatory cytokine responses during the first week. However, marked CSF metabolic dysregulation emerged by 1 month post infection. Initiating ART early, specifically at 3 dpi, normalized these neurometabolic abnormalities. These findings demonstrate that CSF metabolomic shifts can occur independently of overt neuroinflammation during the early stages of viral seeding. These results support initiating ART as early as possible after perinatal HIV exposure to prevent the brain viral reservoir seeding and limit long-term neurological sequelae.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762929","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":"Correction to “Gliovascular alterations in sporadic and familial Alzheimer's disease: APOE3 Christchurch homozygote glioprotection”","authors":"","doi":"10.1111/bpa.70138","DOIUrl":"10.1111/bpa.70138","url":null,"abstract":"&lt;p&gt;\u0000 &lt;span&gt;Henao-Restrepo, J&lt;/span&gt;, &lt;span&gt;López-Murillo, C&lt;/span&gt;, &lt;span&gt;Valderrama-Carmona, P&lt;/span&gt;, &lt;span&gt;Orozco Santa, N&lt;/span&gt;, &lt;span&gt;Gomez, J&lt;/span&gt;, &lt;span&gt;Gutiérrez-Vargas, J&lt;/span&gt;, et al. &lt;span&gt;Gliovascular alterations in sporadic and familial Alzheimer's disease: &lt;i&gt;APOE3&lt;/i&gt; Christchurch homozygote glioprotection&lt;/span&gt;. &lt;i&gt;Brain Pathol&lt;/i&gt;. &lt;span&gt;2023&lt;/span&gt;; &lt;span&gt;33&lt;/span&gt;(&lt;span&gt;2&lt;/span&gt;):e13119. https://doi.org/10.1111/bpa.13119\u0000 &lt;/p&gt;&lt;p&gt;1. The description of the human samples did not fully describe the criteria used to select cases included in each experimental analysis. In the Materials and Methods section (“2.1 Human samples”), the following sentence should be added after “…comorbidities (Table 1 and Table S1)”:&lt;/p&gt;&lt;p&gt;“Postmortem cases included in each experiment were selected according to tissue availability and suitability for the specific analyses performed. A proportion of the postmortem cases overlapped with those included in our previous publications [&lt;span&gt;1, 2&lt;/span&gt;], reflecting the use of the same finite brain bank collection and the selection of tissue according to its availability and suitability for the different analyses performed.”&lt;/p&gt;&lt;p&gt;2. The methodological description did not include specific information regarding the processing of the &lt;i&gt;APOE3&lt;/i&gt; Christchurch tissue. In the Materials and Methods section (“2.2 Immunohistochemistry and immunofluorescence”), the following paragraph should be added before the sentence, “Samples were fixed and cut to 50 μm thick for Nissl staining and immunolabeling”:&lt;/p&gt;&lt;p&gt;“Prior to sectioning, postmortem brain tissue underwent fixation according to the routine procedures of the University of Antioquia Brain Bank. Pre-analytical handling varied depending on tissue availability and prior processing history. Some tissue fragments underwent a period of formalin fixation before transfer to 4% paraformaldehyde for 72 h, with replacement of the fixative every 24 h, whereas others were fixed directly in 4% paraformaldehyde for the same period prior to immunohistochemistry and immunofluorescence. The &lt;i&gt;APOE3&lt;/i&gt; Christchurch brain tissue was processed according to the latter workflow and became available during the final immunostaining series conducted for this study. This pre-analytical difference was specific to the immunostaining experiments performed during the final staining series and did not apply to the AT8, Aβ, Aquaporin-4 immunohistochemistry, or Aquaporin-4/lectin/GFAP immunofluorescence experiments, in which the &lt;i&gt;APOE3&lt;/i&gt; Christchurch case was processed together with the remaining postmortem cases. All tissue sections included in the corresponding quantitative analyses were subsequently processed, stained, acquired, and analyzed using the same protocols, imaging settings, and predefined quantitative criteria.”&lt;/p&gt;&lt;p&gt;3. The legends to Figure 8A and A′ did not disclose that representative Claudin-5 immunohistochemical images had been previousl","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811989","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":"A 58-year-old woman experiencing occasional dizziness, impaired awareness, and deep feeling of fear","authors":"Alessandro Selvaggini,&nbsp;Sabrina Rossi,&nbsp;Marco Brollo,&nbsp;Sabina Barresi,&nbsp;Laurino Licia,&nbsp;Lorenzo Nicolè","doi":"10.1111/bpa.70095","DOIUrl":"10.1111/bpa.70095","url":null,"abstract":"&lt;p&gt;A 58-year-old woman experienced episodes of dizziness and impaired awareness of her surroundings, preceded by an intense feeling of fear. Her history had started 5 years earlier when, after the exclusion of a vascular disorder by a brain CT scan, these episodes were interpreted as possible migraines with aura. Due to their gradual increase in frequency over time, a brain MRI was performed, which revealed a 2.5-cm blurred multinodular lesion localized in the right hippocampus and amygdala. The lesion showed mild hypointensity in T1-weighted sequences and hyperintensity in T2-FLAIR sequences, without perilesional edema, contrast enhancement or diffusion restriction on DWI. An MRI spectroscopy documented a choline peak without a myo-inositol peak association. The radiological findings overall suggested a low-grade neoplasm (Figure 1). Given the persistence of the symptoms, the patient underwent craniotomy with gross total resection of the lesion. After the surgery, the patient experienced mild receptive and expressive aphasia, which is gradually resolving. No seizures have been recorded during subsequent follow-up.&lt;/p&gt;&lt;p&gt;Histopathological examination showed fragments of hippocampal cortex and white matter. At low power, the parenchyma appeared uneven due to the presence of pale somewhat confluent nodular areas (Figure 2A, Box 1). At medium magnification, the pale nodules displayed a mildly increased cellularity with cells featuring large, eccentric, nuclei with one or more nucleoli and abundant, finely granular and eosinophilic cytoplasm, resembling neuronal elements. The cells were embedded in a loose fibrillar matrix and showed frequent cytoplasmic or pericellular vacuolar changes (Figure 2B,C). No mitoses were observed. Ki-67 proliferative index was about 1%. By immunohistochemistry, the neoplastic cells were positive for OLIG2 (Figure 2D) and weakly positive for synaptophysin (Figure 2F), while negative for chromogranin, NeuN (Figure 2E) and neurofilaments; GFAP was positive in the matrix but not in the neoplastic cells; CD34 was restricted to vessels; NSE was negative in the cells but highlighted more clearly the nodular pattern at low magnification. The clinico-pathological features overall suggested the diagnosis of multinodular and vacuolating neuronal tumor (MVNT). A pathogenic mutation (p.Gln56_Val60del) in exon 2 of the &lt;i&gt;MAP2K1&lt;/i&gt; gene was found (TruSight Oncology 500, Illumina), further supporting the diagnosis. Interestingly, the lesion carried an additional pathogenic variant (p.Ile774Tyrfs*5) in exon 10 of the &lt;i&gt;ATR&lt;/i&gt; gene. Both mutations were present at a low variant allele frequency (i.e., 2.5% and 4%, respectively) in a specimen with 30%–40% tumor cellularity.&lt;/p&gt;&lt;p&gt;Multinodular and vacuolating neuronal tumor (MVNT), CNS WHO grade 1.&lt;/p&gt;&lt;p&gt;MVNT is a rare neoplasm, with fewer than 60 pathology-proven cases reported in the English literature to date [&lt;span&gt;1&lt;/span&gt;], only a minority providing molecular characterization. MVNT","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572557","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":"Gliomas with pleomorphic and pseudopapillary features (GPAP) are circumscribed tumors with targetable mutations, prolonged survival, and frequent tumor predisposition.","authors":"Alberto Picca, Valeria Barresi, Aude Trinquet, Luca Bertero, Lucia Nichelli, Guillaume Chotard, Michèle Bernier, Thomas Gareau, Salah Eddine Oussama Kacimi, Jaydutt Bhalshankar, Mathilde Filser, Julien Masliah-Planchon, Marta Iollo, Henri Malaize, Bertrand Mathon, Luc Bauchet, Kifah Khouri, Besma Barka, Hélène Madry, Sabrina Rossi, Evelina Miele, Giuseppe Kenneth Ricciardi, Catherine Carpentier, Irina Coin, Marc Sanson, Mehdi Touat, Caroline Dehais, Alessia Pellerino, Roberta Rudà, Paola Cassoni, Valérie Rigau, Emmanuelle Uro-Coste, Karima Mokhtari, Ahmed Idbaih, Patrick R Benusiglio, Franck Bielle","doi":"10.1111/bpa.70153","DOIUrl":"10.1111/bpa.70153","url":null,"abstract":"<p><p>DNA methylation profiling of CNS tumors led to the identification of HPAP (high-grade glioma with pleomorphic and pseudopapillary features), a recently proposed entity with variable morphology, recurrent MAP-kinase pathway activating events, and longer survival compared to glioblastoma. We aimed to independently validate and further characterize this entity. We retrieved a multicentric cohort of gliomas compatible with HPAP and performed t-SNE dimensionality reduction on their DNA methylation profile. Clinical, radiological, histological, and molecular data were reviewed. Twenty tumors clustering with previously reported HPAP cases were identified. Median age at diagnosis was 37 years. Radiologically, the tumors appeared as expansive lesions with heterogeneous enhancement and frequent cysts. Histologically, they were well-circumscribed, with papillary and pleomorphic features variably present. Marked histological signs of aggressivity were present in seven. Immunostainings showed expression of GFAP, OLIG2, and CD34. All cases were IDH1/2 wildtype and pMGMT unmethylated. Recurrently mutated genes included TP53, ATRX, RB1, and BRAF. Five patients had germline pathogenic variants in genes associated with hereditary tumor predisposition syndromes (MLH1, BRCA2, CHEK2, NF2, RB1). All patients underwent surgical resection, but subsequent management was heterogeneous. Ten-year estimated survival was 85%. CDKN2A homozygous deletion seemed to identify more aggressive tumors. In conclusion, our data suggest the existence of a novel entity of circumscribed gliomas with long-term survival despite possible high-grade histological presentation, for which we propose the nomenclature \"Gliomas with pleomorphic and pseudopapillary features\" with a spectrum encompassing provisory grade 2 and 3. A proper identification could guide treatment choices.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70153"},"PeriodicalIF":5.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079927","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 transcriptomic analysis of neurons at the glioma infiltration front: A case study.","authors":"Kaishi Satomi, Hirokazu Takami, Hiromi Onizuka, Kuniaki Saito, Takako Yoshioka, Motoo Nagane, Yutaka Suzuki, Koichi Ichimura, Junji Shibahara","doi":"10.1111/bpa.70154","DOIUrl":"10.1111/bpa.70154","url":null,"abstract":"<p><p>Spatial transcriptomics reveals localized IGFBP5 expression and TGFβ-related signaling in neurons within glioma-infiltrated tissue.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70154"},"PeriodicalIF":5.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073587","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":"Correction to \"Molecular and clinical features of a Japanese medulloblastoma cohort: Subgroup-specific prognostic stratification using economical/accessible diagnostic methods\".","authors":"","doi":"10.1111/bpa.70148","DOIUrl":"10.1111/bpa.70148","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70148"},"PeriodicalIF":5.0,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13594783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015911","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}