Antonio Dono, Diego Pichardo-Rojas, Leonardo Mendoza Mora, Pavel S Pichardo-Rojas, Luis A Marin-Castañeda, Abril Carrillo, Adrian Coria Medrano, Yoshua Esquenazi, Leomar Y Ballester
{"title":"MTAP immunohistochemistry as a surrogate marker of CDKN2A loss in brain tumors: A meta-analysis and literature review.","authors":"Antonio Dono, Diego Pichardo-Rojas, Leonardo Mendoza Mora, Pavel S Pichardo-Rojas, Luis A Marin-Castañeda, Abril Carrillo, Adrian Coria Medrano, Yoshua Esquenazi, Leomar Y Ballester","doi":"10.1093/jnen/nlaf033","DOIUrl":"10.1093/jnen/nlaf033","url":null,"abstract":"<p><p>Given the known relationship between CDKN2A homozygous deletion (HD) and worsened outcomes in both meningiomas and IDH-mutant astrocytomas, it is paramount to identify CDKN2A HD for accurate risk stratification of patients. Multiple array platforms can detect CDKN2A HD. However, these methods are expensive and are not readily available at every institution. To address this, we conducted a meta-analysis and literature review to evaluate 5'-methylthioadenosine phosphorylase (MTAP) expression determined by immunohistochemistry (IHC) as a surrogate of CDKN2A HD. Our study analyzed 7 cohort studies, 3 of which focused on meningiomas encompassing a total of 87 patients; and 4 studies were conducted on infiltrating glioma patients, consisting of 423 patients. Our results show that despite utilizing different MTAP IHC clones, the results among all studies showed consistently good sensitivity and specificity. The overall sensitivity and specificity of MTAP IHC as a surrogate of CDKN2A HD was excellent with 92.3% and 97.5%, respectively. These results were maintained when MTAP IHC was evaluated in distinct tumor types. MTAP IHC is a good surrogate marker for identifying CDKN2A HD in infiltrating gliomas and meningiomas. MTAP IHC implementation would allow correct integrated diagnosis for institutions that lack DNA sequencing.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"600-610"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12199257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meike S Thijssen, Maartje Massen, Jaleesa R M van der Meer, Marion J Gijbels, Iryna V Samarska, Manon van Engeland, Matty P Weijenberg, Piet A van den Brandt, Kim M Smits, Werend Boesmans, Veerle Melotte
{"title":"Clinicopathological characterization of enteric glia in colorectal cancer: Insights from a population-based cohort.","authors":"Meike S Thijssen, Maartje Massen, Jaleesa R M van der Meer, Marion J Gijbels, Iryna V Samarska, Manon van Engeland, Matty P Weijenberg, Piet A van den Brandt, Kim M Smits, Werend Boesmans, Veerle Melotte","doi":"10.1093/jnen/nlaf067","DOIUrl":"https://doi.org/10.1093/jnen/nlaf067","url":null,"abstract":"<p><p>Enteric glia contribute to the regulation of mucosal homeostasis and intestinal immunity. Enteric glia dysfunction is linked to various gastrointestinal disorders. We aimed to characterize the phenotype of enteric glia in colorectal cancer (CRC) and examine their association with CRC patient characteristics. Healthy, adenoma, and tumor tissues from CRC patients were immunohistochemically stained for the glial markers S100B and glial fibrillary acidic protein (GFAP). GFAP-positive enteric glia were identified within carcinoma tissue stroma but were absent in normal mucosa or adenoma tissue from the same patients. S100B staining was detected in all sample types. Two CRC patient cohorts (n = 447 and n = 324) were analyzed for GFAP staining and to assess association of GFAP immunoreactivity with patient characteristics. This indicated that GFAP-positive cells might be associated with tumor localization and median survival. High-density GFAP staining was associated with improved survival in the study cohort (HR = 0.56; P = 0.030), but not the validation cohort (HR = 0.85; P = 0.606). These findings suggest that CRC induces GFAP expression in enteric glia. While prognostic value of GFAP could not be confirmed, future studies are needed to elucidate the role of enteric glia in CRC prognosis and progression.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chang Liu, Athanasios S Alexandris, Marjan Gharagozloo, Thomas Garton, Peter A Calabresi, Vassilis E Koliatsos
{"title":"Temporal progression of axonal degeneration in the visual system in experimental autoimmune encephalomyelitis: Insights from high-resolution neuropathology.","authors":"Chang Liu, Athanasios S Alexandris, Marjan Gharagozloo, Thomas Garton, Peter A Calabresi, Vassilis E Koliatsos","doi":"10.1093/jnen/nlaf073","DOIUrl":"https://doi.org/10.1093/jnen/nlaf073","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is characterized by inflammation, demyelination, and axonal degeneration in the CNS, leading to progressive neurological disability is generally regarded as an autoimmune disorder. Visual impairment, a frequent symptom, results from damage to retinal ganglion cells (RGCs) and their axons in the anterior visual pathway. Using the experimental autoimmune encephalomyelitis (EAE) model in mice, we used several methods, including high-resolution neuropathology with a novel immunohistochemical technique on ultrathin sections, to characterize axonal pathology and demyelination, terminal disruption, perikaryal degeneration, and visual acuity. Electron microscopy demonstrated early axonopathy and myelin splitting, progressing to severe degradation of axons and myelin sheaths. Severe transport deficits in the optic nerve correlated with loss of labeling of retinocollicular terminals. Visual acuity, assessed by optomotor response (OMR), significantly declined at peak stage in the EAE group and remained impaired throughout the course of disease. These findings reveal the temporal progression of neurodegeneration with a dying-back pattern in EAE and emphasize the importance of early intervention to prevent permanent damage. They also point to the importance of novel methods in generating new insights in classical models of neurological disease.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hoang-Tuong Nguyen-Hao, Jie Liu, Mario Novelli, Dhiraj Maskey, Raymond S Schwartz, Oscar Harari, Greg T Sutherland
{"title":"Quantification of Alzheimer disease neuropathology using tissue microarrays.","authors":"Hoang-Tuong Nguyen-Hao, Jie Liu, Mario Novelli, Dhiraj Maskey, Raymond S Schwartz, Oscar Harari, Greg T Sutherland","doi":"10.1093/jnen/nlaf064","DOIUrl":"https://doi.org/10.1093/jnen/nlaf064","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is characterized by the hallmark pathologies of β-amyloid plaques and neurofibrillary tangles (NFTs), which vary across brain regions and between affected individuals. As a rapid research method to quantify hallmark pathologies and their relationships with the surrounding cytoarchitecture across the brain, we trialed tissue microarrays (TMAs) in combination with multiplex immunofluorescence and semi-automated image analysis. We assayed the hallmark pathologies across grey and white matter sites of 11 different brain regions and quantified astrocytes, microglia, and neurons in four AD cases and four age- and gender-matched controls. The results demonstrated that 2 mm cores differentiated AD-affected individuals from healthy donors. Regional amyloid loads corroborated the established spread from the neocortex to allocortex, pontine, and occasionally cerebellar regions. Similarly, NFT counts matched the pattern predicted by Braak staging. Contrasting with the two hallmark pathologies, regional cell numbers were similar between cases and controls although cell counts were affected by variable staining quality. These results suggest that TMAs in combination with multiplex immunofluorescence and image analysis offer a powerful research tool for the rapid assessment of brain-wide AD neuropathological change in postmortem tissue. This quick assessment allows an informed selection of regions for more comprehensive investigations.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yara Al Ojaimi, Samira Osman, Hugo Alarcan, Patrick Emond, Charlotte Veyrat-Durebex, Debora Lanznaster, Sandra Meme, Rudy Clemencon, Laurent Galineau, Philippe Corcia, Christian Andres, Patrick Vourc'h, Fabienne Masse, Fabrice Trovero, Hélène Blasco
{"title":"Identification of disease-associated molecular signatures in the Prp-TDP-43A315T mouse model of ALS: Toward preclinical biomarker development.","authors":"Yara Al Ojaimi, Samira Osman, Hugo Alarcan, Patrick Emond, Charlotte Veyrat-Durebex, Debora Lanznaster, Sandra Meme, Rudy Clemencon, Laurent Galineau, Philippe Corcia, Christian Andres, Patrick Vourc'h, Fabienne Masse, Fabrice Trovero, Hélène Blasco","doi":"10.1093/jnen/nlaf071","DOIUrl":"https://doi.org/10.1093/jnen/nlaf071","url":null,"abstract":"<p><p>Identifying disease-related molecular signatures that can be used as biomarkers is critical for the development of preclinical therapies for amyotrophic lateral sclerosis (ALS). In this study, we focused on the Prp-TDP-43A315T transgenic mouse model of ALS to explore peripheral and central molecular alterations associated with disease progression. Prp-TDP-43A315T transgenic (Tg) and C57BL/6J wild-type mice were monitored from 50 to 400 postnatal days. One cohort assessed phenotypic parameters and MRI activity at 3 timepoints, ie, before (T0), at disease onset (T1), and at end-stage (T2). A second cohort validated findings from the first using omics analyses of tissues to examine ALS-related markers. Tg mice showed reduced body weight, decreased grip strength and tail position, and increased gait impairment at T1. Changes in (p)TDP-43, NRF2, GFAP, and pAMPK expression were noted in brain samples from the second cohort at T1. Metabolomic and lipidomic analyses revealed shifts in specific molecules in the brain and muscle of Tg mice. These data highlight individual differences in ALS pathology and adaptive responses to TDP-43-induced damage. This model provides valuable insights into TDP-43 proteinopathies and presents an innovative method for analyzing pathophysiological pathways through dried blood spot analysis, thereby expanding its applicability across various research fields.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leyla Canbeldek, Raquel T Yokoda, Lakshmi S Kulumani Mahadevan, Yamato Suemitsu, Jorge Samanamud, Cheyanne C Slocum, Carolina Maldonado-Díaz, Satomi Hiya, Kevin Clare, Raymund L Yong, Melissa Umphlett, Nadejda M Tsankova, John F Crary, Jamie M Walker, Thomas P Naidich, Timothy E Richardson
{"title":"Antemortem radiologic and histopathologic presentation of Marchiafava-Bignami disease.","authors":"Leyla Canbeldek, Raquel T Yokoda, Lakshmi S Kulumani Mahadevan, Yamato Suemitsu, Jorge Samanamud, Cheyanne C Slocum, Carolina Maldonado-Díaz, Satomi Hiya, Kevin Clare, Raymund L Yong, Melissa Umphlett, Nadejda M Tsankova, John F Crary, Jamie M Walker, Thomas P Naidich, Timothy E Richardson","doi":"10.1093/jnen/nlaf074","DOIUrl":"https://doi.org/10.1093/jnen/nlaf074","url":null,"abstract":"<p><p>Marchiafava-Bignami disease (MBD) is a rare disorder, characterized by demyelination and cystic necrosis of the corpus callosum; it is typically seen in the setting of chronic alcoholism but may also occur with severe malnutrition. Clinical features include altered mental status, loss of consciousness, dysarthria, spasticity, ataxia, and seizures. To our knowledge, only 1 case of MBD with antemortem histology has been reported in the literature. Herein, we describe the clinical, radiologic, and histopathologic features of 2 new cases with corpus callosum demyelination consistent with MBD that were identified on antemortem biopsy; 1 was related to chronic alcoholism and the other was in the setting of severe malnutrition. Imaging studies showed that the initial lesions involved the full thickness of the corpus callosum with later evolution into the characteristic linear zone of necrosis in the mid-third of the corpus callosum. There was additional evidence of extracallosal involvement in both patients. Biopsies in both patients demonstrated numerous macrophages with myelin debris in their cytoplasm and relative axonal preservation, although there was some axonal loss in areas with the densest collection of macrophages. These findings highlight the clinical and radiographic progression in 2 cases of biopsy-proven MBD.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neuromuscular pathology and mitochondrial dysfunction in sorbitol dehydrogenase gene-related distal hereditary motor neuropathies.","authors":"Zhenyu Li, Xujun Chu, Yize Li, Zhiying Xie, Meng Yu, Jianwen Deng, He Lv, Wei Zhang, Qiang Gang, Zhaoxia Wang, Lingchao Meng, Yun Yuan","doi":"10.1093/jnen/nlaf070","DOIUrl":"https://doi.org/10.1093/jnen/nlaf070","url":null,"abstract":"<p><p>Biallelic variants in sorbitol dehydrogenase (SORD) have been reported to be a major cause of autosomal recessive distal hereditary motor neuropathy (dHMN). In this study, the clinical and pathological features of 10 patients with SORD gene-related dHMN are reported. Homozygous c.757delG variant was detected in 6 patients while c.757delG, c.786 + 1G>A, c.218C>T, and a novel c.104T>A compound heterozygous variants were observed in the others. Serum sorbitol, xylitol, and D-arabinitol were measured by gas chromatography-mass spectrometry; increased sorbitol and xylitol, and decreased D-arabinitol were identified. Sural nerve biopsies showed mild loss of large, myelinated fibers, and a few thin myelinated fibers. Skeletal muscle biopsies exhibited a neurogenic pattern with vacuoles, tubular aggregates, and abnormal mitochondria. Proteomic analyses of muscle tissue were performed to explore potential mechanisms. Complex I deficiency was dominant in the proteomic analysis and the malic acid/oxaloacetic acid ratio was significantly higher in the patients than in controls. In summary, SORD gene-related dHMN is a systemic disorder of carbohydrate metabolism with subclinical myopathologic changes, including tubular aggregates and vacuoles. Mitochondrial complex I deficiency, may be a key mechanism in SORD gene-related dHMN.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Riley H Lochner, Suzanne Z Powell, Kar-Ming Fung, Yi J Zhang, David Baskin, Ivo W Tremont-Lukats, Rupen Desai, Ian F Dunn, James D Battiste, Maya Hrachova, Jayson Hardcastle, Amir Nazem, Stephanie A Smoley, Matthew Isaacson, Surendra Dasari, Mallika Gandham, Patrick J Cimino, Martha Quezado, Zied Abdullaev, Drew Pratt, Kenneth Aldape, Robert Jenkins, Cristiane M Ida
{"title":"FGFR1 fusions in genomically and epigenetically bona fide glioblastoma, IDH-wildtype.","authors":"Riley H Lochner, Suzanne Z Powell, Kar-Ming Fung, Yi J Zhang, David Baskin, Ivo W Tremont-Lukats, Rupen Desai, Ian F Dunn, James D Battiste, Maya Hrachova, Jayson Hardcastle, Amir Nazem, Stephanie A Smoley, Matthew Isaacson, Surendra Dasari, Mallika Gandham, Patrick J Cimino, Martha Quezado, Zied Abdullaev, Drew Pratt, Kenneth Aldape, Robert Jenkins, Cristiane M Ida","doi":"10.1093/jnen/nlaf068","DOIUrl":"https://doi.org/10.1093/jnen/nlaf068","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Monica Ospina-Romero, Shaan M Raza, Komal Shah, Martha Quezado, Kenneth Aldape, Maria A Gubbiotti
{"title":"Expanding the differential diagnosis for dural-based spindle cell neoplasms: A report of a rare GLI1-altered mesenchymal tumor of the CNS.","authors":"Monica Ospina-Romero, Shaan M Raza, Komal Shah, Martha Quezado, Kenneth Aldape, Maria A Gubbiotti","doi":"10.1093/jnen/nlaf069","DOIUrl":"https://doi.org/10.1093/jnen/nlaf069","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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