Neuropathology最新文献

{"title":"Ependymoma-like tumor with mesenchymal differentiation (ELTMD) with ZFTA:NCOA1 fusion: A diagnostic challenge.","authors":"Pranav Dorwal, Christine White, Anna Fn Goh, Amit Kumar, Jane McEniery, Rick Walker, Thomas Robertson","doi":"10.1111/neup.12952","DOIUrl":"10.1111/neup.12952","url":null,"abstract":"<p><p>Ependymal tumors are classified based on their location, histology, and molecular characteristics. Supratentorial ependymomas (ST-EPNs) are a group of circumscribed supratentorial gliomas, which usually have pathogenic fusions involving either zinc finger translocation associated (ZFTA) (formerly C11orf95) or YAP1. A subtype of ependymoma was recently described and labeled ependymoma-like tumors with mesenchymal differentiation (ELTMDs). We describe a case of a 5-year-old boy who presented with a right frontal tumor. The diagnosis was challenging, and a correct diagnosis could only be reached after reanalysis of methylation data with a more recent version of the classifier and RNA fusion testing, which revealed ZFTA:NCOA1 (nuclear receptor coactivator 1) fusion. There are only a handful of cases of this entity, which is being reported for its rarity and the diagnostic challenge it poses.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"216-221"},"PeriodicalIF":1.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71484276","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 myxopapillary ependymoma with predominant giant cell morphology: A rare entity with comprehensive genomic profiling and review of literature","authors":"Bryan Morales‐Vargas, Hassan Saad, Daniel Refai, Matthew Schniederjan, Zied Abdullaev, Kenneth Aldape, Malak Abedalthagafi","doi":"10.1111/neup.12977","DOIUrl":"https://doi.org/10.1111/neup.12977","url":null,"abstract":"In the evolving landscape of ependymoma classification, which integrates histological, molecular, and anatomical context, we detail a rare case divergent from the usual histopathological spectrum. We present the case of a 37‐year‐old man with symptomatic spinal cord compression at the L3–L4 level. Neuroradiological evaluation revealed an intradural, encapsulated mass. Histologically, the tumor displayed atypical features: bizarre pleomorphic giant cells, intranuclear inclusions, mitotic activity, and a profusion of eosinophilic cytoplasm with hyalinized vessels, deviating from the characteristic perivascular pseudorosettes or myxopapillary patterns. Immunohistochemical staining bolstered this divergence, marking the tumor cells positive for glial fibrillary acidic protein and epithelial membrane antigen with a characteristic ring‐like pattern, and CD99 but negative for Olig‐2. These markers, alongside methylation profiling, facilitated its classification as a myxopapillary ependymoma (MPE), despite the atypical histologic features. This profile underscores the necessity of a multifaceted diagnostic process, especially when histological presentation is uncommon, confirming the critical role of immunohistochemistry and molecular diagnostics in classifying morphologically ambiguous ependymomas and exemplifying the histological diversity within MPEs.","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"100 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140626555","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":"Acute respiratory failure caused by brainstem demyelinating lesions in an older patient with an atypical relapsing autoimmune disorder","authors":"Shoko Hongo, Hiroshi Shimizu, Etsuji Saji, Akihiro Nakajima, Kouichirou Okamoto, Izumi Kawachi, Osamu Onodera, Akiyoshi Kakita","doi":"10.1111/neup.12976","DOIUrl":"https://doi.org/10.1111/neup.12976","url":null,"abstract":"An 84‐year‐old man presented with somnolence, dysphagia, and right hemiplegia, all occurring within a month, approximately one year after initial admission due to subacute, transient cognitive decline suggestive of acute disseminated encephalomyelitis involving the cerebral white matter. Serial magnetic resonance imaging (MRI) studies over that period revealed three high‐intensity signal lesions on fluid‐attenuated inversion recovery images, appearing in chronological order in the left upper and left lower medulla oblongata and left pontine base. Despite some clinical improvement following methylprednisolone pulse therapy, the patient died of respiratory failure. Autopsy revealed four fresh, well‐defined lesions in the brainstem, three of which corresponded to the lesions detected radiologically. The remaining lesion was located in the dorsal medulla oblongata and involved the right solitary nucleus. This might have appeared at a later disease stage, eventually causing respiratory failure. Histologically, all four lesions showed loss of myelin, preservation of axons, and infiltration of lymphocytes, predominantly CD8‐positive T cells, consistent with the histological features of autoimmune demyelinating diseases, particularly the confluent demyelination observed in the early and acute phases of multiple sclerosis (MS). In the cerebral white matter, autoimmune demyelination appeared superimposed on ischemic changes, consistent with the cerebrospinal fluid (CSF) and MRI findings on initial admission. No anti‐AQP4 or MOG antibodies or those potentially causing autoimmune encephalitis/demyelination were detected in either the serum or CSF. Despite several similarities to MS, such as the relapsing–remitting disease course and lesion histology, the entire clinicopathological picture in the present patient, especially the advanced age at onset and development of brainstem lesions in close proximity within a short time frame, did not fit those of MS or other autoimmune diseases that are currently established. The present results suggest that exceptionally older individuals can be affected by an as yet unknown inflammatory demyelinating disease of the CNS.","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"42 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578425","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":"Rare dual‐genotype IDH mutant glioma: Review of previously reported cases and two new cases of true “oligoastrocytoma”","authors":"Isabella Sutherland, John DeWitt, Alissa Thomas","doi":"10.1111/neup.12975","DOIUrl":"https://doi.org/10.1111/neup.12975","url":null,"abstract":"In 2016, the World Health Organization (WHO) eliminated “oligoastrocytoma” from the classification of central nervous system (CNS) tumors, in favor of an integrated histologic and molecular diagnosis. Consistent with the 2016 classification, in the 2021 classification, oligodendrogliomas are defined by mutations in isocitrate dehydrogenase (<jats:italic>IDH</jats:italic>) with concurrent 1p19q codeletion, while astrocytomas are <jats:italic>IDH</jats:italic> mutant tumors, usually with <jats:italic>ATRX</jats:italic> loss. In 2007, a 24‐year‐old man presented with a brain tumor histologically described as astrocytoma, but with molecular studies consistent with an oligodendroglioma, <jats:italic>IDH</jats:italic> mutant and 1p19q‐codeleted. Years later, at resection, pathology revealed an astrocytoma, with variable <jats:italic>ATRX</jats:italic> expression and mutations of <jats:italic>IDH</jats:italic>, <jats:italic>ATRX</jats:italic>, <jats:italic>TP53</jats:italic>, and <jats:italic>TERT</jats:italic> by DNA sequencing. Fluorescence in situ hybridization studies confirmed 1p19q codeletion in sections of the tumor shown to histologically retain <jats:italic>ATRX</jats:italic> expression. Separately, in 2017, a 36‐year‐old woman presented with a frontal brain tumor with pathology consistent with an oligodendroglioma, <jats:italic>IDH</jats:italic> mutant and 1p19q‐codeleted. Two years later, pathology revealed an astrocytoma, <jats:italic>IDH1</jats:italic> mutant, with <jats:italic>ATRX</jats:italic> loss. These two cases likely represent the rare occurrence of dual‐genotype <jats:italic>IDH</jats:italic> mutant infiltrating glioma. Nine cases of dual‐genotype <jats:italic>IDH</jats:italic> mutant glioma were previously reported in the literature. We present two cases in which this distinct molecular phenotype is present in a tumor in the same location with surgeries at two points in time, both with 1p19q codeletion and <jats:italic>ATRX</jats:italic> loss at the time of resection. Whether this represents a true “collision tumor” or genetic switching over time is not known, but the co‐occurrence of these hybrid mutations supports a diagnosis of dual‐genotype <jats:italic>IDH</jats:italic> mutant glioma.","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"122 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140602400","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":"Association between hypothalamic Alzheimer's disease pathology and body mass index: The Hisayama study","authors":"Kaoru Yagita, Hiroyuki Honda, Tomoyuki Ohara, Sachiko Koyama, Hideko Noguchi, Yoshinao Oda, Ryo Yamasaki, Noriko Isobe, Toshiharu Ninomiya","doi":"10.1111/neup.12974","DOIUrl":"https://doi.org/10.1111/neup.12974","url":null,"abstract":"The hypothalamus is the region of the brain that integrates the neuroendocrine system and whole-body metabolism. Patients with Alzheimer's disease (AD) have been reported to exhibit pathological changes in the hypothalamus, such as neurofibrillary tangles (NFTs) and amyloid plaques (APs). However, few studies have investigated whether hypothalamic AD pathology is associated with clinical factors. We investigated the association between AD-related pathological changes in the hypothalamus and clinical pictures using autopsied brain samples obtained from deceased residents of a Japanese community. A total of 85 autopsied brain samples were semi-quantitatively analyzed for AD pathology, including NFTs and APs. Our histopathological studies showed that several hypothalamic nuclei, such as the tuberomammillary nucleus (TBM) and lateral hypothalamic area (LHA), are vulnerable to AD pathologies. NFTs are observed in various neuropathological states, including normal cognitive cases, whereas APs are predominantly observed in AD. Regarding the association between hypothalamic AD pathologies and clinical factors, the degree of APs in the TBM and LHA was associated with a lower body mass index while alive, after adjusting for sex and age at death. However, we found no significant association between hypothalamic AD pathology and the prevalence of hypertension, diabetes, or dyslipidemia. Our study showed that a lower BMI, which is a poor prognostic factor of AD, might be associated with hypothalamic AP pathology and highlighted new insights regarding the disruption of the brain–whole body axis in AD.","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"64 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578506","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":"Retrospective neuropathological diagnosis of TDP-43 proteinopathies: Factors affecting immunoreactivity of phosphorylated TDP-43 in fixed post-mortem brain tissue.","authors":"Andrew C Robinson, Yvonne S Davidson, James Minshull, Imogen Lally, Liam Walker, David M A Mann, Federico Roncaroli","doi":"10.1111/neup.12937","DOIUrl":"10.1111/neup.12937","url":null,"abstract":"","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"173-179"},"PeriodicalIF":2.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10277695","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":"Novel mutations in FLVCR1 cause tremors, sensory neuropathy with retinitis pigmentosa.","authors":"Zhenyu Li, Yize Li, Xujun Chu, Kang Du, Yuwei Tang, Zhiying Xie, Meng Yu, Jianwen Deng, He Lv, Wei Zhang, Zhaoxia Wang, Lingchao Meng, Yun Yuan","doi":"10.1111/neup.12936","DOIUrl":"10.1111/neup.12936","url":null,"abstract":"<p><p>The mutations of the feline leukemia virus subgroup C receptor-related protein 1 (FLVCR1) cause ataxia with retinitis pigmentosa. Recent studies indicated a large variation in the phenotype of FLVCR1-associated diseases. In this report, we describe an adult male who manifested first with tremors in his third decade, followed by retinitis pigmentosa, sensory ataxia, and sensory neuropathy in his fourth decade. While retinitis pigmentosa and sensory ataxia are well-recognized features of FLVCR1-associated disease, tremor is rarely described. Whole-exome sequencing revealed novel compound heterozygous pathogenic FLVCR1 variants: c.498 G > A; p.(Trp166*) and c.369 T > G; p.(Phe123Leu). In addition, we have highlighted the ultrastructural abnormalities of the sural biopsy in this patient.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"87-95"},"PeriodicalIF":2.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9837415","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":"An autopsy case of intravascular large B-cell lymphoma showing a rapid transition to embolic strokes with occlusion of the major cerebral arteries.","authors":"So Tando, Tadashi Kimura, Ryo Mizuhara, Natsuko Yuki, Akira Yoshioka, Hisashi Takahashi, Rei Yasuda, Kyoko Itoh","doi":"10.1111/neup.12940","DOIUrl":"10.1111/neup.12940","url":null,"abstract":"<p><p>Intravascular large B-cell lymphoma can induce central nervous system manifestations, including strokes, due to small-vessel occlusion caused by lymphoma cells. However, involvement in large-sized vessels is rare. Here, we present an unusual autopsy case of an 88-year-old man showing a rapid transition from multiple strokes due to small vessel occlusion, typical of intravascular lymphoma, to progressive embolic strokes caused by the occlusion of major cerebral arteries. Magnetic resonance angiography demonstrated the major cerebral arteries associated with those multiple progressive strokes, including the right posterior cerebral artery, left anterior cerebral artery, and right middle cerebral artery, but the detectability was poor. A random skin biopsy at the abdomen confirmed the diagnosis of intravascular large B-cell lymphoma. The patient died 106 days after hospitalization despite intensive treatment. An autopsy revealed broad liquefactive necrosis in the area governed by the major cerebral arteries and multiple small infarctions caused by intravascular lymphoma cells in the small-sized vessels. In addition, the major cerebral arteries showed multiple thromboembolism with partial organization and clusters of intravascular lymphoma cells. Notably, those cells were shown aggregated and attached along the vascular wall of the basilar artery, which might have caused focal hypercoagulation in the near vessels. This aggregation might have disseminated widely in the other major cerebral arteries. Moreover, the cluster of intravascular lymphoma cells in the basilar artery was positive for tumor necrosis factor α, and similar histopathology findings were observed in the splenic veins. However, the pathogenesis of this rare phenomenon involving these cells remains unknown. From a clinical perspective, we should consider the possibility that intravascular lymphoma cells may provoke similar progressive embolic strokes.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"135-146"},"PeriodicalIF":2.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9964285","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":"Atypical TDP-43 proteinopathy clinically presenting with progressive nonfluent aphasia: A case report.","authors":"Yuki Suzuki, Tadashi Adachi, Kentaro Yoshida, Kenta Taneda, Mayuko Sakuwa, Masato Hasegawa, Ritsuko Hanajima","doi":"10.1111/neup.12942","DOIUrl":"10.1111/neup.12942","url":null,"abstract":"<p><p>Progressive nonfluent aphasia (PNFA) is a form of frontotemporal lobar degeneration (FTLD) caused by tau and transactive response DNA-binding protein of 43 kDa (TDP-43) accumulation. Here we report the autopsy findings of a 64-year-old right-handed man with an atypical TDP-43 proteinopathy who presented with difficulties with speech, verbal paraphasia, and dysphagia that progressed over the 36 months prior to his death. He did not show pyramidal tract signs until his death. At autopsy, macroscopic brain examination revealed atrophy of the left dominant precentral, superior, and middle frontal gyri and discoloration of the putamen. Spongiform change and neuronal loss were severe on the cortical surfaces of the precentral, superior frontal, and middle frontal gyri and the temporal tip. Immunostaining with anti-phosphorylated TDP-43 revealed neuronal cytoplasmic inclusions and long and short dystrophic neurites in the frontal cortex, predominantly in layers II, V, and VI of the temporal tip, amygdala, and transentorhinal cortex. Immunoblot analysis of the sarkosyl-insoluble fractions showed hyperphosphorylated TDP-43 bands at 45 kDa and phosphorylated C-terminal fragments at approximately 25 kDa. The pathological distribution and immunoblot band pattern differ from the major TDP-43 subtype and therefore may represent a new FTLD-TDP phenotype.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"154-160"},"PeriodicalIF":2.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10288808","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":"Epstein-Barr virus-positive monoclonal lymphoplasmacytic proliferation associated with neurosyphilis in an immunocompetent patient: A case report.","authors":"Takashi Hibiya, Kiyotaka Nagahama, Yoshie Matsumoto, Kuniaki Saito, Nobuyoshi Sasaki, Keiichi Kobayashi, Akiyasu Otsu, Teppei Shimasaki, Kengo Takeuchi, Yoshiaki Shiokawa, Motoo Nagane, Junji Shibahara","doi":"10.1111/neup.12934","DOIUrl":"10.1111/neup.12934","url":null,"abstract":"<p><p>Syphilis is an infectious disease caused by the spirochete bacterium Treponema pallidum. Neurosyphilis results from the infection of the nervous system with Treponema pallidum, which can occur at any stage of syphilis. Neurosyphilis is often overlooked because of its rarity. Early-stage neurosyphilis with brain mass formation is rare. We present a case of early-stage neurosyphilis with prominent Epstein-Barr virus (EBV)-positive monoclonal lymphoplasmacytic proliferation in an immunocompetent patient. A 36-year-old man presented with a chief complaint of a progressively worsening headache, a newly developed skin rash, and a fever. Magnetic resonance imaging showed a mass lesion, which measured 18 mm in diameter, in the left frontal lobe of the cerebrum. The patient underwent an emergency operation to remove the abscess. A pathological investigation revealed complex findings. There was an abscess in the cerebrum. Lymphoplasmacytic meningitis was also noted. In addition, a vaguely nodular lesion, which was composed of plasmacytoid and lymphoid cells, was observed around the abscess. Immunohistochemically, an anti-Treponema pallidum antibody revealed numerous Treponemas around the abscess. In situ hybridization revealed that the plasmacytoid and lymphoid cells were Epstein-Barr encoding region (EBER)-positive; κ-positive cells were significantly more prevalent than λ-positive cells, suggesting light-chain restriction. Postoperatively, parenteral antibiotics were administered for four weeks. The patient has been free of recurrence for two years since the surgery. No association between neurosyphilis and EBV-positive lymphoplasmacytic proliferation has ever been reported. Mass formation in early-stage neurosyphilis is an exceptionally rare event. The present case indicates that in syphilis patients, lymphoproliferative disorders that lead to mass formation may be caused by concomitant EBV reactivation. Furthermore, when treating patients with mass lesions of the central nervous system, it is important to check their medical history and perform laboratory screening for infectious diseases to avoid overlooking syphilis infections.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"104-108"},"PeriodicalIF":2.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9761081","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}