Brain Pathology最新文献

{"title":"CRYAB is compromised in pathologically affected oligodendrocytes in multiple system atrophy.","authors":"Finula I Isik, Jen-Hsiang T Hsiao, Felicia Xaveria Suteja, Shrey Shahdadpuri, Nicolas Dzamko, Glenda M Halliday, Woojin Scott Kim, YuHong Fu","doi":"10.1111/bpa.70112","DOIUrl":"https://doi.org/10.1111/bpa.70112","url":null,"abstract":"<p><p>CRYAB is hypermethylated and colocalizes with α-synuclein in multiple system atrophy oligodendrocytes.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70112"},"PeriodicalIF":6.2,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148041240","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":"A 67-year-old man with a spinal extramedullary mass.","authors":"Marcella Callea, Francesco Costa, Rosina Paterra, Valeria Barresi","doi":"10.1111/bpa.70105","DOIUrl":"https://doi.org/10.1111/bpa.70105","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70105"},"PeriodicalIF":6.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833974","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":"RE: Comments on cIMPACT-NOW Update 11","authors":"Henning Leske,&nbsp;Richard Doughty,&nbsp;Pitt Niehusmann","doi":"10.1111/bpa.70061","DOIUrl":"10.1111/bpa.70061","url":null,"abstract":"&lt;p&gt;We read with great interest cIMPACT-NOW Update 11, in which the consortium provides diagnostic recommendations for glioblastoma, IDH-wildtype (GBM); diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (pHGG); and posterior fossa ependymal tumors. The authors are to be commended for addressing unresolved challenges identified since the release of the 5th edition of the WHO Classification of Tumours of the Central Nervous System (WHO CNS5, 2021). While the update offers valuable guidance, we would like to comment on several aspects that would benefit from clarification, closer alignment with WHO CNS5, and refined wording to avoid diagnostic ambiguity in routine practice.&lt;/p&gt;&lt;p&gt;WHO CNS5 specifies an age of “≥55 years” in the absence of &lt;i&gt;IDH1&lt;/i&gt; p.R132H immunoreactivity, classic GBM histology, non-midline location, and no history of a pre-existing lower-grade glioma as sufficient for a GBM diagnosis. The repeated use of “&gt;55 years” in Update 11—implying a shift from ≥55 to ≥56 years—appears to be a typographical inconsistency, which should be confirmed by the authors [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;WHO CNS5 also recommends that ATRX-negative tumors should undergo additional molecular testing to exclude &lt;i&gt;IDH1&lt;/i&gt;/&lt;i&gt;2&lt;/i&gt; and/or H3 alterations, regardless of age. Update 11 highlights H3 p.K28me3 immunostaining as a practical method to exclude diffuse midline glioma, H3 K27-altered (DMG)—useful not only for H3 p.K28M-mutant cases, as mentioned by the authors, but also for those driven by &lt;i&gt;EZHIP&lt;/i&gt; overexpression or &lt;i&gt;EGFR&lt;/i&gt; sequence alterations, as retained nuclear expression virtually excludes DMG.&lt;/p&gt;&lt;p&gt;The committee's recommendation that &lt;i&gt;TERT&lt;/i&gt;-promoter mutations in IDH-wildtype astrocytic gliomas with low-grade histology should not, in isolation, define GBM is prudent to prevent overtreatment in a subset of cases, particularly given recently characterized tumors such as adult-type diffuse high-grade glioma, IDH-wildtype, subtype F (HGG-F) with less aggressive clinical behavior. However, the suggestion that some tumors with “higher-grade features that do not meet histologic criteria for glioblastoma” be diagnosed descriptively (not elsewhere classified, NEC) introduces ambiguity. It remains unclear whether such cases with absence of necrosis and vascular proliferation—despite high mitotic activity and isolated &lt;i&gt;TERT&lt;/i&gt;-promoter mutation—do not justify a GBM diagnosis.&lt;/p&gt;&lt;p&gt;The statement that isolated &lt;i&gt;EGFR&lt;/i&gt; amplification or +7/−10 signature alone is not sufficient for a GBM diagnosis in patients &lt;40 years is reasonable, but somewhat rigid. It should be stressed that these are expert recommendations intended to guide pathological practice. However, since the authors also note that diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (pHGG) as one of the major differential diagnoses can occur “in adults up to 70 years of age,” this rule of thumb may be adapted to local resources and shou","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 3","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958877","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":"Reply to comments on cIMPACT-NOW update 11","authors":"Pieter Wesseling,&nbsp;David N. Louis","doi":"10.1111/bpa.70047","DOIUrl":"10.1111/bpa.70047","url":null,"abstract":"<p>The associated commentary acknowledges that cIMPACT-NOW update 11 addresses areas of significant diagnostic uncertainty and that it provides important interim guidance for CNS tumor classification. The commentary also provides a set of comments and suggestions. In this context, it is important to understand that cIMPACT-NOW update 11 (like all cIMPACT-NOW updates) presents consensus recommendations from multiple experts in the field, with the opinions often following lengthy discussions and the weighing of different possibilities. These debates included whether other recommendations should be provided on particular topics; however, for the paper, the consensus opinions were part of cIMPACT-NOW update 11, but topics that did not yield consensus decisions were not included. Some of these latter, open-ended issues were brought up in the associated commentary. We trust that deliberations for the 6th edition of the WHO Classification of CNS Tumors, which begin in late 2025, will discuss some of these topics again, and the associated commentary provides another set of comments to inform such discussions.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 3","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958849","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":"Alzheimer's disease and mixed pathologies as a hidden contributor to fatal hypothermia: A large-scale forensic autopsy-based study","authors":"Shojiro Ichimata,&nbsp;Koji Yoshida,&nbsp;Ryo Tanaka","doi":"10.1111/bpa.70051","DOIUrl":"10.1111/bpa.70051","url":null,"abstract":"<p>There is a paucity of autopsy-based studies providing detailed neuropathological characteristics of fatal hypothermia cases, particularly in trauma-associated cases. Hence, this study investigated 2054 serial autopsy cases in which histopathological examination of all organs, including the brain, could be performed. We identified 168 cases (75 female and 93 male patients) of fatal hypothermia and examined the clinical and neuropathological characteristics in these cases. Patients aged ≥65 years constituted 80% of the cohort (135 cases). Cognitive impairment (CI) was identified in 39% of cases with available clinical histories, and approximately half of these cases were presumed to have developed hypothermia while wandering, based on clinical history and the circumstances of discovery. Alzheimer's disease was the most commonly identified pathology, affecting 40% of the total and approximately two-thirds of patients aged ≥80 years. CI caused by multiple pathologies, especially two, was more frequently observed than by a single pathology. The most common manner of exposure to cold temperatures was accidents (120 cases), including 35 cases with multiple traumatic injuries, most likely resulting from falls. In these cases, the trauma was considered the primary cause of immobility, leading to subsequent exposure to cold environments. Importantly, 30 (86%) of these trauma-associated cases showed one or more neuropathological conditions, and CI was documented in 13, with four presumed to have fallen while wandering. Notable neuropathological manifestations were also observed in eight of the 33 cases of patients aged less than 65 years. Our results demonstrate that neurodegenerative diseases, especially Alzheimer's disease, are underlying conditions in fatal hypothermia in the elderly and in relatively younger individuals, suggesting that they may contribute to its onset. These findings highlight the necessity for comprehensive neuropathological examination in all forensic autopsy cases of hypothermia.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 3","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145629935","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":"Vessel-associated microglia are differentially activated and distributed in relation to systemic infection and Alzheimer's disease","authors":"Oliver Milner,&nbsp;Robert A. Fisher,&nbsp;Daniel J. Asby,&nbsp;Stephen Cross,&nbsp;Delphine Boche,&nbsp;J. Scott Miners","doi":"10.1111/bpa.70052","DOIUrl":"10.1111/bpa.70052","url":null,"abstract":"<p>Vessel-associated microglia (VAM) are an integral part of the neurovascular unit and have recently been implicated in the pathophysiology of cerebrovascular injury and blood–brain barrier (BBB) leakiness in Alzheimer's disease (AD). In this neuropathological study, we explored the hypothesis that the distribution and activation of VAM are altered in AD in the presence of systemic infection, associated with cerebrovascular dysfunction. We studied VAM density in the temporal cortex and underlying white matter from AD and age-matched controls with and without terminal systemic infection (SI) (<i>n</i> = 15 per group). The area of VAM labelled with microglial markers (Iba1, HLA-DR, CD68) was quantified in proximity to CD31-labelled microvessels within three predefined regions: contact VAM, proximity &lt;15 μm, and parenchymal &gt;15 μm. The relationships between VAM and previously measured brain cytokine levels and biochemical markers of cerebral perfusion (MAG:PLP1, endothelin-1) and BBB leakiness (VEGF-A and fibrinogen), were explored in a subset of cases. Compared to controls, the relative area of Iba1+ VAM was higher in SI and in AD. The area of HLA-DR+ VAM was higher in AD only. The area of Iba1+ VAM that expressed CD68, a marker of phagocytosis, was higher in both AD and AD + SI. Iba1+ and HLA-DR+ VAM correlated inversely with anti-inflammatory cytokines (IL-10, IL-23) in AD and positively with pro-inflammatory cytokines (IL-6, IL-23, GM-CSF, IL-17) in AD + SI. Iba1+ VAM density correlated positively with endothelin-1, VEGF-A and fibrinogen in controls. HLA-DR+ VAM density correlated positively with Aβ_1-42 in both controls and AD, and inversely with PDGFRβ and VCAM-1 in AD. Our data reveal the distribution of VAM is elevated in AD, and altered in the presence of systemic infection, which together are likely to be independent and synergistic contributors to cerebrovascular dysfunction in AD.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 3","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145629927","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":"14-3-3σ up-regulation in the temporal cortex associates with tau pathology and reactive astroglia in Lewy body disorders","authors":"Laura Marsal-García,&nbsp;Jorge Mena,&nbsp;Carol-Ann Lao,&nbsp;David Adamuz,&nbsp;Laura Arnaldo,&nbsp;Cristina Carrato,&nbsp;Alex Menendez,&nbsp;Daniela Samaniego,&nbsp;Dolores Vilas,&nbsp;Lourdes Ispierto,&nbsp;Anna Planas,&nbsp;Ramiro Alvarez,&nbsp;Pau Pastor,&nbsp;Katrin Beyer","doi":"10.1111/bpa.70059","DOIUrl":"10.1111/bpa.70059","url":null,"abstract":"<p>The 14-3-3 protein family plays a crucial role in cellular signaling and neuronal survival. Although 14-3-3 isoforms have been involved in the etiology of some neurodegenerative disorders, their role remains poorly understood in alpha-synucleinopathies. In this study, we wanted to characterize 14-3-3 gene expression patterns in the brain and periphery of patients with Lewy body pathology (LBP). We analyzed messenger RNA (mRNA) expression of all seven 14-3-3 isotypes in the temporal cortex and caudate nucleus of brains with pure and common LBP, as well as in cerebrospinal fluid, peripheral blood, and platelets. Stratifin (SFN) protein expression was assessed by immunohistochemistry and enzyme-linked immunosorbent assay. Effects of SFN overexpression on astrocyte activation were investigated in vitro. In the temporal cortex of LBP patients, six out of seven 14-3-3 genes were significantly downregulated, while SFN was markedly up-regulated. SFN protein localized to neurofibrillary tangles in the parahippocampal region and reactive astrocytes in white matter. In vitro, SFN treatment induced biphasic changes in astrocytic glial fibrillary acidic protein expression, suggesting a role in glial activation. Peripheral analysis revealed no significant 14-3-3 mRNA changes in blood, but platelet expression patterns inversely correlated with brain tissue; six isoforms were up-regulated, and SFN was strongly downregulated in dementia with Lewy bodies (DLB) platelets. Our findings revealed an important shift in 14-3-3 isotype expression in the temporal cortex of LBP patients, where SFN up-regulation reflected its colocalization with tau pathology and astrocytic reactivity. The inverse expression profile in platelets in DLB highlights their potential as accessible biomarkers for molecular changes occurring in the brain.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 3","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767282","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":"Identification of novel FGFR2::TXLNB Fusion in a polymorphous low-grade neuroepithelial tumor of the young","authors":"Sha-Sha Hu,&nbsp;Tian-Yuan Tan,&nbsp;Wei Yan,&nbsp;Bo Wang","doi":"10.1111/bpa.70063","DOIUrl":"10.1111/bpa.70063","url":null,"abstract":"<p>We report a novel <i>FGFR2::TXLNB</i> fusion in a child with hippocampal PLNTY. This fusion likely drives tumorigenesis via homodimerization and activation of MAPK/PI3K pathways, expanding PLNTY's molecular spectrum and suggesting a potential therapeutic target.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 3","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843185","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 5-month-old infant with a pineal tumor","authors":"Fabien Forest,&nbsp;Martin Hasselblatt,&nbsp;Fanélie Barral-Clavel,&nbsp;Alix Clemenson,&nbsp;Sandrine Thouvenin,&nbsp;Claire Berger,&nbsp;Anne Mc Leer,&nbsp;Catherine Godfraind","doi":"10.1111/bpa.70066","DOIUrl":"10.1111/bpa.70066","url":null,"abstract":"&lt;p&gt;A 4-month-old child was referred to our institution due to partial epilepsy accompanied by asthenia, downward gaze deviation, and strabismus. Brain magnetic resonance imaging (MRI) showed a well delineated tumor of the pineal region in the posterior part of the third ventricle with acute hydrocephalus. The tumor was in isosignal in T1 and T2 with contrast enhancement after gadolinium injection measuring 18 mm (Figure 1). A surgical excision was decided through suboccipital transtentorial approach; during surgery, the tumor could not be completely removed because of venous invasion and because of a huge Galen vein preventing access to part of the tumor.&lt;/p&gt;&lt;p&gt;Histopathological analysis revealed a highly cellular tumor composed of sheets and trabecular structures made of cells with hyperchromatic nuclei and high nuclear cytoplasmic ratio, with numerous mitoses and areas of necrosis (Figure 2A and Box 1). Tubular structures containing melanin pigment were observed, as confirmed by Fontana-Masson staining (Figure 2B inset). No ganglion cell, nor rhabdomyoblastic cells, nor cells with striated muscle differentiation were found after examination, but cartilaginous-like hyalinized stroma areas were found (Figure 2C). Tumor cells stained positive for synaptophysin (Figure 1D). Expression of SMARCB1/INI1 and SMARCA4/BRG1 was retained. Stain for Lin28 was negative, while stains for Melan-A and HMB45 were weak and focal (Figure 2E,F). The Ki67/MIB1 proliferation index was 70%. Methylation testing on formalin-fixed paraffin-embedded tissue, on a tumor with tumor purity at 80% and 500 ng of DNA input with Infinium Methylation EPIC v2.0. The DNA methylation profile of the tumor did not group with any of the DKFZ classifier (version 12.8). The NIH classifier grouped the tumor with neuroblastic embryonal tumors with a score at 0.976 without a sufficient score to assess a specific tumor type. On t-SNE analysis, the DNA methylation profile grouped in the vicinity of other pineal tumors and normal pineal gland (Figure 2G).&lt;/p&gt;&lt;p&gt;Pineal anlage tumor, CNS WHO grade 4.&lt;/p&gt;&lt;p&gt;Pineal anlage tumor is regarded as a morphological variant of pineoblastoma. The histopathological hallmarks are the presence of a neuroectodermal component constituted of pineoblastoma-like cells with neuronal, glial, or melanin-containing cells combined to an ectomesenchymal component containing rhabdomyoblasts, cartilage, or smooth muscle. In the English literature, less than 30 cases have been reported [&lt;span&gt;1&lt;/span&gt;]. Histopathological examination is not specific, with embryonal-like neoplastic cells growing as sheets or trabeculae, but the information of the location of the tumor is important for the diagnosis. The main differential diagnosis is atypical teratoid/rhabdoid tumors and embryonal tumor with multilayered rosettes. Pineoblastomas, so as pineal anlage tumor, retain expression of SMARCB1(INI1) and SMARCA4 (BRG1) and do not express LIN28A.&lt;/p&gt;&lt;p&gt;The molecular alterations of pinea","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 3","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848870","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 17-year-old male with chronic epilepsy status post remote functional hemispherectomy","authors":"Claire Voyles,&nbsp;Elliot Stalter,&nbsp;Melissa M. Blessing,&nbsp;Osorio Lopes Abath Neto","doi":"10.1111/bpa.70070","DOIUrl":"10.1111/bpa.70070","url":null,"abstract":"&lt;p&gt;A 17-year-old male with infant-onset epilepsy refractory to multiple antiseizure medications had a history of right functional hemispherectomy performed at 6 months of age after demonstration of seizure activity localized to the right frontal lobe. A brain MRI performed at 4 months of age revealed a mildly enlarged right lateral ventricle but was otherwise unremarkable. Pathology from the surgical specimen reportedly identified a focal cortical dysplasia. Follow-up visits over the years showed that the patient was nonverbal and wheelchair-dependent, with left homonymous hemianopsia and spasticity, but the epilepsy was mostly controlled with only rare brief seizures. At 17 years of age, he was found unresponsive and pronounced dead at home. Recent clinical history included a respiratory illness accompanied by vomiting, fever, and fatigue. A complete autopsy was performed, and bronchopneumonia of the left lung was established as the likely cause of death.&lt;/p&gt;&lt;p&gt;Gross examination of the brain revealed asymmetric cerebral hemispheres due to reduced volume of the right hemisphere, which contained a large area of cavitation spanning the frontal and temporal lobes and sparing the basal ganglia and thalamus, consistent with the history of functional hemispherectomy (Figure 1) (Box 1). Histopathological examination of sections from both hemispheres showed numerous haphazardly arranged astrocytes with eosinophilic ameboid to granular cytoplasmic inclusions (Figure 2A,B), variably distributed throughout all layers of the neocortex, and not present in deep gray matter structures. The inclusions were positive for GFAP (Figure 2C) and negative for NeuN (Figure 2D), OLIG2, PU.1, PAS, and neurofilament. There were increased numbers of corpora amylacea, highlighted by PAS.&lt;/p&gt;&lt;p&gt;Hyaline protoplasmic astrocytopathy.&lt;/p&gt;&lt;p&gt;Hyaline protoplasmic astrocytopathy (HPA) is a rare, underrecognized, and incompletely understood neuropathologic entity, with fewer than 70 cases reported in the literature, including both surgical and autopsy specimens [&lt;span&gt;1&lt;/span&gt;]. First described by Alois Alzheimer in 1910 under a different designation [&lt;span&gt;2&lt;/span&gt;], HPA has been associated with epilepsy, particularly in the setting of Aicardi syndrome, neurodevelopmental disorders, and less commonly, dementia.&lt;/p&gt;&lt;p&gt;Histopathologically, HPA is characterized by hyaline ameboid to granular astrocytic inclusions, mostly juxtanuclear, distributed throughout all cortical layers. The affected astrocytes are often enlarged and haphazardly oriented, and the inclusions are sharply demarcated and eosinophilic, distinguished from corpora amylacea or neuronal storage material by their cellular localization. Inset of Figure 2B shows a reproduction of Alzheimer's original publication showing abnormal ameboid astrocytes. The hyaline astrocytes are rarely reported in the superficial white matter, hippocampus, and basal ganglia, and are absent in other deep gray matter, cerebellum, brainstem, or sp","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"36 3","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970678","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}