Neuropathology最新文献

{"title":"Unprecedented Combination of Rare Degenerative Pathologies in an Octogenarian Ex-Football Player.","authors":"Shelley L Forrest, Nusrat Sadia, Mozhgan Khodadadi, Charles Tator, Robin Green, Maria Carmela Tartaglia, Gabor G Kovacs","doi":"10.1111/neup.70004","DOIUrl":"10.1111/neup.70004","url":null,"abstract":"<p><p>A 79-year-old former professional football player presented with language deficits and cognitive changes. A year later, he had difficulty completing sentences, and 3 years after onset, was reduced to one-word answers. He developed severe apathy and agitation, and became more impulsive. He eventually became mute and had difficulty with walking and balance. The patient had mild repetitive head injury while playing football and three concussions. Magnetic resonance imaging revealed left > right frontotemporal atrophy. Duration of illness was 6 years. Neuropathology revealed an unexpected number and diversity of degenerative pathologies, including chronic traumatic encephalopathy (CTE, high level), high level Alzheimer's disease neuropathologic change (A3B3C3), limbic Lewy body disease, cerebral amyloid angiopathy (type 2), argyrophilic grain disease (Stage 2), and neuronal intranuclear hyaline inclusion body disease. In addition, there was selective and asymmetric involvement of the corticospinal tract with globular oligodendroglial tau pathology corresponding to globular glial tauopathy (Type II). The patchy and irregular accentuation of cortical tau pathology, particularly in the depths of sulci and accumulation around blood vessels, allows the diagnosis of CTE-neuropathologic change. This diagnosis correlated with the past medical history of multiple concussions. In addition, the patient had an unprecedented number and combination of additional degenerative pathologies, including those that are rare, and how they contributed to the clinical symptoms is difficult to interpret. Globular glial tauopathy Type II is a rare disorder that has been mostly reported in association with progressive supranuclear gaze palsy, and these observations support the notion that globular glial tauopathy Type II is an independent entity with isolated corticospinal tract involvement. These observations highlight that rare disorders can occur in the same individual and be overlooked, especially when there is more obvious pathology. It is essential for neuropathologists to consider an extensive array of neuropathological examinations when assessing patients with neurodegenerative disorders.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"e70004"},"PeriodicalIF":1.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of late-life blood pressure with CERAD, Braak, and Thal: Findings from the National Alzheimer's coordinating center neuropathology dataset.","authors":"Mo-Kyung Sin, N Maritza Dowling, Jeffrey M Roseman, Ali Ahmed, Edward Zamrini","doi":"10.1111/neup.13029","DOIUrl":"10.1111/neup.13029","url":null,"abstract":"<p><p>Mid-life high blood pressure (BP) is a risk factor for Alzheimer's disease (AD). CERAD amyloid β (Aβ) plaques, Braak tau neurofibrillary tangles, and Thal Aβ plaque location are major scoring systems for quantifying neuropathological features of AD. We examined the association of late-life systolic BP (SBP) with CERAD, Braak, and Thal in the National Alzheimer's Coordinating Center (NACC) Neuropathology Dataset. Of 1978 participants with data on CERAD, 762 had scores 0-1 (none to sparse) and 1216 had 2-3 (moderate to frequent). Of 1947 with data on Braak, 411 had stages 0-II (normal to mild) and 1536 had III-VI (moderately to very severe). Of 2132 with data on Thal, 438 had phases 0-I, 428 II-III, and 1266 IV-V. Using the mean of the last four SBP before death, SBP was categorized into <120 (references), 120-139, and ≥140 mmHg. Age-sex-adjusted ORs (95% CIs) associated with SBP ≥140 mmHg for CERAD 2-3 and Braak III-VI were 1.37 (1.03, 1.83, P = 0.03) and 1.26 (0.89, 1.78, P = 0.20), respectively. Similar association was observed for Thal II-III and IV-V. These associations essentially remained unchanged after additional adjustment for APOE and Lewy Body pathology. These findings suggest that higher late-life SBP is associated with markers of presence and severity of neuropathological features of AD. Further studies with larger sample sizes are necessary to confirm the findings.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"e13029"},"PeriodicalIF":1.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two Brothers With ADSS1 Myopathy: A Report of Clinical, Radiological, and Autopsy Findings.","authors":"Yuka Hama, Terunori Sano, Yasushi Oya, Chihiro Matsumoto, Yuji Nakayama, Yoshihiko Saito, Aritoshi Iida, Makoto Shibuya, Yuko Saito, Ichizo Nishino, Yuji Takahashi, Masaki Takao","doi":"10.1111/neup.70008","DOIUrl":"10.1111/neup.70008","url":null,"abstract":"<p><p>ADSS1 myopathy, previously known as adenylosuccinate synthetase-like 1 (ADSSL1) myopathy, is an autosomal recessive muscle disease caused by variants in ADSS1 (adenylosuccinate synthase 1). ADSS1 myopathy is complicated by respiratory muscle weakness or cardiomyopathy as well as limb muscle weakness. We analyzed two siblings with ADSS1 myopathy, both harboring compound heterozygous pathogenic variants (c.781G>A/c.919delA) in ADSS1 and provided details of their phenotypes together with muscle imaging and autopsy findings. Although it was reported that ADSS1 myopathy usually began with lower limb muscle weakness, our cases showed early involvement of the cervical paraspinal muscle, triceps brachii muscle, flexor digitorum superficialis and profundus muscles, rectus abdominis muscle, gluteus maximus and medius muscles, and cardiomyopathy. While a previous study reported that the trunk and hip muscles were relatively spared, atrophy of paraspinal muscles, gluteus medius and maximus muscles, and adductor muscles were observed. Our two siblings allowed for long-term follow-up and will be useful reference cases. We evaluated the frequency of fibers with nemaline bodies in various autopsied muscles and found that the ratio of fibers with nemaline bodies was lower compared to other nemaline myopathies. Postmortem examination revealed, for the first time, nemaline bodies in the diaphragm and myocardium, associated with respiratory failure and cardiomyopathy.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"e70008"},"PeriodicalIF":1.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029897","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":"Glioblastoma, IDH-wildtype manifesting as intracranial hemorrhage: A case report highlighting the clinical utility of digital polymerase chain reaction in integrated diagnoses.","authors":"Yukino Nikai, Kaishi Satomi, Kuniaki Saito, Miho Gomyo, Yuko Matsushita, Kenichiro Kato, Kiyotaka Nagahama, Aya Isomura, Akimasa Hayashi, Yuki Yamagishi, Nobuyoshi Sasaki, Keiichi Kobayashi, Kazuhiro Tsuchiya, Motoo Nagane, Koichi Ichimura, Junji Shibahara","doi":"10.1111/neup.13025","DOIUrl":"10.1111/neup.13025","url":null,"abstract":"<p><p>The manifestation of glioblastoma, IDH-wildtype (GB) as intracranial hemorrhage (ICH) presents diagnostic and therapeutic challenges. Molecular characteristics, including TERT promoter mutation, EGFR amplification, and chromosome 7 gain/10 loss, were incorporated to diagnose GB in the fifth edition of the World Health Organization Classification of Tumors of the Central Nervous System. When molecular analyses fail to detect low fractions of these genetic alterations, the integrated diagnosis of GB can be enigmatic. This case report describes a 58-year-old man presenting with ICH, masking an underlying GB. Initial histopathology of the evacuated hematoma revealed a small number of atypical glial cells, but a definitive diagnosis was deferred. Subsequent surgery and molecular analysis, including digital polymerase chain reaction (dPCR), confirmed the presence of a TERT C228T mutation in the promoter area, leading to an integrated diagnosis of GB. The patient experienced a favorable clinical outcome following surgery, radiation, temozolomide, and tumor-treating field therapy, without recurrence after 50 months. This case underscores the importance of meticulous histological examination of ICH and exemplifies the clinical utility of dPCR as a complementary diagnostic tool. The effectiveness of dPCR is particularly noteworthy, even in scenarios with minimal tumor cell content, reinforcing its value in the integrated diagnosis of GB.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"e13025"},"PeriodicalIF":1.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921335","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 case of rhabdoid meningioma originating from the optic nerve.","authors":"Jing Liu, Ziling Yan, Fan Lin, Xia Liu","doi":"10.1111/neup.13028","DOIUrl":"10.1111/neup.13028","url":null,"abstract":"<p><p>We report a rare case of rhabdoid meningioma (RM) originating from the optic nerve in a 57-year-old female. The tumor exhibited rhabdoid or epithelioid histology and harbored BAP1 inactivation mutations. Optic nerve meningioma typically originates from the outer meningeal cells of the optic nerve within the optic canal and is usually benign, with most cases classified as meningothelial or transitional meningiomas. This is the first reported case of RM involving the optic nerve, presenting with World Health Organization (WHO) central nervous system (CNS) grade 1 histological features but without CDKN2A/B homozygous deletions or telomerase reverse transcriptase promoter mutations, though harboring a BAP1 deletion. Despite being classified as a low-grade tumor by current standards, the rapid recurrence and progression observed underscore the importance of reporting this case to enhance awareness among pathologists and reduce misdiagnoses.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"e13028"},"PeriodicalIF":1.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047344","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":"Non-Neoplastic Lesions of the Ependyma: A Neuropathological Overview.","authors":"Masayuki Shintaku","doi":"10.1111/neup.70014","DOIUrl":"10.1111/neup.70014","url":null,"abstract":"<p><p>Non-neoplastic lesions of the ependyma have been neglected to date in comparison with neoplastic lesions derived from the ependyma, that is, ependymoma. The ependyma has a simple structure: mono-layered cuboidal cells covering the surface of the cerebral ventricles and the central canal of the spinal cord. In this review, the histopathological appearances of various non-neoplastic ependymal lesions are shown based on the author's personal experience, along with a review of the relevant literature. Following the introductory remarks about the normal histology and functions of ependymal cells including tanycytes, non-neoplastic lesions are then presented including, obliteration of the spinal central canal; the \"ventriculus terminalis\"; shedding of ependymal cells and \"granular ependymitis\"; \"ependymal incorporation\"; ependymal cells in hydrocephalus; ependymal reactions to various noxious stimuli; ependymal changes in cerebral dysgenesis; infections involving ependymal cells; glio-ependymal cyst; and finally, various intracellular inclusions in ependymal cells. Non-neoplastic ependymal lesions are intriguing and merit further investigations, which may provide deeper understanding of various brain lesions and of ependymal neoplasms.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"e70014"},"PeriodicalIF":1.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192051","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":"Multiple Neuropathologies Underly Hippocampal Subfield Atrophy in a Case With a Slowly Progressive Amnestic Syndrome: Challenging the Notion of Pure LATE-NC.","authors":"Hossam Youssef, Rodolfo G Gatto, Nha Trang Thu Pham, David Jones, Ronald C Petersen, Mary M Machulda, Jennifer L Whitwell, Keith A Josephs","doi":"10.1111/neup.70000","DOIUrl":"10.1111/neup.70000","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the leading cause of dementia in the elderly, marked by abnormal protein buildup (beta-amyloid and tau) resulting in neuronal loss, especially in the medial temporal lobe and other limbic regions. The presence of transactive response DNA binding protein 43 (TDP-43) immunoreactive inclusions in medial temporal lobe regions has also been associated with neuroimaging changes in limbic regions. It has been proposed that hypometabolism in limbic regions on [¹⁸F] fluorodeoxyglucose positron emission tomography (FDG-PET) in a patient with a slowly evolving amnestic syndrome may be a signature of the presence of TDP-43. In this context, we observed an 86-year-old Caucasian female with dementia characterized by a slowly evolving amnestic syndrome, along with focal medial temporal atrophy evident on MRI and hypometabolism in limbic regions on FDG-PET. The patient subsequently died and underwent an autopsy. We performed detailed neuroimaging and digital neuropathological analyses of the hippocampal subfields to better understand the relationship between clinico-imaging findings and histopathology. In addition to TDP-43, we identified three other pathological processes in the medial temporal lobe: sequestosome-1/p62, argyrophilic grain disease (AGD), and primary age-related tauopathy (PART). Hippocampal subfield volumes and rates of atrophy were no different from those of matched healthy controls, except for the atrophy rate in cornu ammonis 1 (CA1). Digital histopathology revealed the relative highest burden of pathology for p62, followed by TDP-43, AGD, and PART in CA1. Multiple pathological processes appear to have contributed to the hippocampal atrophy and hypometabolism in our patient with a slowly progressive amnestic syndrome.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"e70000"},"PeriodicalIF":1.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracellular and Extracellular Localization of Transthyretin and Its Association With Amyloid-β in Alzheimer's Disease Brains.","authors":"Yuri Mizuno, Hiroyuki Honda, Hideko Noguchi, Sachiko Koyama, Chie Kikutake, Toshiharu Ninomiya, Ryo Yamasaki, Noriko Isobe","doi":"10.1111/neup.70015","DOIUrl":"10.1111/neup.70015","url":null,"abstract":"<p><p>Transthyretin (TTR) can bind to Aβ and prevent the formation of Aβ fibrils in vitro; it is thus a highly interesting molecule in the field of Alzheimer's disease (AD) research. However, the distribution of TTR and its affinity to Aβ in both healthy human brains and those of AD patients remain unclear. We therefore examined TTR in human brains using postmortem brain samples. Paraffin sections and extracted protein samples were prepared from AD and control (non-AD) brains. Immunohistochemistry was performed to detect TTR expression patterns, and immunofluorescent staining was used to reveal the relationships between the intracellular and extracellular localizations of TTR and Aβ. We also performed western blotting for TTR using brain extracts. In immunohistochemical staining of the human brain, TTR signal was detected not only in extracellular tissue but also in the cytoplasm of neurons and glia. The TTR-positive area was significantly greater in AD brains than in non-AD brains. However, expression of TTR transcripts did not differ between AD and non-AD brains in our previously obtained RNA-sequencing and microarray data. Immunofluorescent staining with multiple antibodies revealed that TTR was co-localized with Aβ in the cytoplasm of neurons. In extracellular Aβ plaques, TTR presented in the same region but was not co-localized with dense Aβ fibrils. Together, our results indicate that TTR is widely expressed in the human brain rather than being limited to the choroid plexus and that TTR is more abundant in AD brains. Our results also suggest that the affinity between TTR and Aβ changes depending on the structure of Aβ. Our data will be valuable for the future development of TTR-related AD preventative methods and medications.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"e70015"},"PeriodicalIF":1.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192050","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":"Pituitary Blastoma: Expanding the Spectrum of Histopathological Findings in a Young Adult With DICER1 Mutation.","authors":"Sumanta Das, Bheru Dan Charan, Shrinidhi Nathany, Rakesh Kumar Gupta, Mehar Chand Sharma, Salman Shaikh, Rana Patir, Sunita Ahlawat","doi":"10.1111/neup.70017","DOIUrl":"10.1111/neup.70017","url":null,"abstract":"<p><p>Pituitary blastoma is a rare embryonal tumor of the pituitary gland, typically occurring in children under 2 years of age and strongly associated with germline DICER1 mutations. Only a limited number of cases have been reported, with very few occurring beyond early childhood. We present the case of a 27-year-old male who presented with severe headaches, vomiting, visual disturbances, and altered behavior. Magnetic resonance imaging revealed a large suprasellar mass with sellar extension, diffusion restriction, and hemorrhagic components. The radiological differential diagnoses included papillary craniopharyngioma, pilocytic astrocytoma, and high-grade glioma. Surgical decompression was performed, and histopathological examination revealed a highly cellular tumor with blastemal, glandular, and rosette-forming components, consistent with pituitary blastoma. Immunohistochemistry showed patchy positivity for OLIG2, synaptophysin, and LIN28A, along with a high Ki-67 proliferation index (~90%). Next-generation sequencing confirmed a pathogenic DICER1 mutation (p.Glu1813Asp, p.Pro817fs), supporting the diagnosis. Unlike most reported cases, which present with Cushing's syndrome or ophthalmoplegia, this patient had an elevated prolactin level, a feature not previously described in pituitary blastoma. The tumor followed an aggressive course, and the patient succumbed within a month post-surgery. This case expands the clinicopathologic spectrum of pituitary blastoma, emphasizing unusual age and known genetic associations, and highlights the need for a high index of suspicion in atypical cases.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"e70017"},"PeriodicalIF":1.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199724","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":"OTX-2 Expression as a Diagnostic Marker for Choroid Plexus Tumors.","authors":"Ayça Erşen Danyeli, Zeynep Hüseyinoğlu, M Memet Özek","doi":"10.1111/neup.70001","DOIUrl":"10.1111/neup.70001","url":null,"abstract":"<p><p>Choroid plexus tumors are neuroepithelium-derived tumors arising in the ventricles of the central nervous system. They are commonly seen in childhood and correspond to low rates in all central nervous system tumors. Due to their rareness and similar histomorphologic features to other tumors, their diagnosis might be challenging. Here, we used the OTX-2 antibody to evaluate the diagnostic role of OTX-2 expression in choroid plexus tumors. We performed a retrospective review of 34 patients operated for choroid plexus tumors in our center between 2011 and 2023. Additionally, as different tumor types are also arising in the ventricles, we selected five cases each of AT/RT, germ cell tumor, ependymoma, and metastatic adenocarcinoma from the pathology archive. Immunohistochemistry conditions were adjusted for each specific antibody based on the manufacturers' recommendations for concentrations and antigen retrieval/blocking. OTX-2, S-100, and transthyretin antibody staining was performed on sections from each case.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"e70001"},"PeriodicalIF":1.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483515","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}