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":"https://doi.org/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":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: Comorbidities in early-onset sporadic versus presenilin-1 mutation-associated Alzheimer disease dementia: Evidence for dependency on Alzheimer disease neuropathological changes.","authors":"","doi":"10.1093/jnen/nlaf030","DOIUrl":"https://doi.org/10.1093/jnen/nlaf030","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997788","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}
Yue Li, Xiujiao Shen, Ji Zhang, Xinyi Xian, Shaoyu Chen, Jing Zeng, Wanming Hu
{"title":"Adult diffuse IDH-wildtype lower-grade gliomas with PDGFRA gain/amplification should be upgraded as glioblastoma.","authors":"Yue Li, Xiujiao Shen, Ji Zhang, Xinyi Xian, Shaoyu Chen, Jing Zeng, Wanming Hu","doi":"10.1093/jnen/nlaf039","DOIUrl":"https://doi.org/10.1093/jnen/nlaf039","url":null,"abstract":"<p><p>We explored the prognostic significance of platelet-derived growth factor receptor α (PDGFRA) gain/amplification in grade 2-4 adult gliomas to assess its value as an upgrading indicator. Fluorescence in situ hybridization was performed to detect PDGFRA gain/amplification in 321 glioma specimens from Sun Yat-sen University Cancer Center (SYSUCC). Data from 1934 cases with available next-generation sequencing results from The Cancer Genome Atlas (TCGA) and cBioPortal were also analyzed. Of the adult grade 2-4 gliomas, 12.15% (39/321), 8.76% (93/1062), and 6.88% (60/872) had PDGFRA gain/amplification in the SYSUCC, TCGA, and cBioPortal cohorts, respectively. Grade 4 glioblastomas had a greater PDGFRA gain/amplification rate than lower-grade gliomas (LGGs) in all cohorts (all P < .05). PDGFRA gain/amplification was associated with older age, greater World Health Organization grade, isocitrate dehydrogenase (IDH)-wildtype, intact 1p/19q, telomerase reverse transcriptase promoter-wildtype, greater Ki67 index, epidermal growth factor receptor amplification, and chromosome 7+/10- alterations. PDGFRA gain/amplification predicted poor overall survival (OS) in grade 2-4 gliomas, particularly IDH-wildtype LGGs, in all cohorts (all P < .05). OS was worse in PDGFRA-amplified IDH-wildtype LGGs than in IDH-wildtype glioblastomas in the cBioPortal (P = .031) and SYSUCC (P = .026) cohorts. PDGFRA gain/amplification predicted poor OS in adult diffuse IDH-wildtype LGGs and may serve as an upgrading indicator.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005934","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}
Barbara Verbraeken, Tomas Menovsky, Rabih Aboukais, Martin Lammens
{"title":"Histological appearance of topical hemostatic agents and materials in neuropathology.","authors":"Barbara Verbraeken, Tomas Menovsky, Rabih Aboukais, Martin Lammens","doi":"10.1093/jnen/nlaf032","DOIUrl":"https://doi.org/10.1093/jnen/nlaf032","url":null,"abstract":"<p><p>Hemostatic agents and other foreign materials are frequently encountered in neuropathology samples. Recognizing these materials is crucial for accurate diagnosis and in the context of adverse events. This article provides an overview of macroscopic and microscopic characteristics of commonly used hemostatic agents and materials in neurosurgery. Samples of sterile hemostatic agents and retrospectively collected pathology slides were examined. Routine histopathological processing, special stains, and polarized light microscopy were utilized to document the appearance of these materials. A total of 22 hemostatic agents and 9 artifacts and foreign bodies were analyzed. Distinct macroscopic and microscopic properties, as well as effects of tissue processing, were documented. Recognizing hemostatic agents and materials is largely dependent on their main constituents. A constituent-based approach for identification of these materials is presented for the practicing neuropathologist.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031881","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}
Angelique D Gonzalez, Yannick N Wadop, Benjamin Danner, Kyra M Clarke, Matthew B Dopler, Ali Ghaseminejad-Bandpey, Sahana Babu, Julie Parker-Garza, Cole Corbett, Mohammad Alhneif, Mallory Keating, Kevin F Bieniek, Gladys E Maestre, Sudha Seshadri, Shahroo Etemadmoghadam, Bernard Fongang, Margaret E Flanagan
{"title":"Digital pathology in tau research: A comparison of QuPath and HALO.","authors":"Angelique D Gonzalez, Yannick N Wadop, Benjamin Danner, Kyra M Clarke, Matthew B Dopler, Ali Ghaseminejad-Bandpey, Sahana Babu, Julie Parker-Garza, Cole Corbett, Mohammad Alhneif, Mallory Keating, Kevin F Bieniek, Gladys E Maestre, Sudha Seshadri, Shahroo Etemadmoghadam, Bernard Fongang, Margaret E Flanagan","doi":"10.1093/jnen/nlaf026","DOIUrl":"https://doi.org/10.1093/jnen/nlaf026","url":null,"abstract":"<p><p>The application of digital pathology tools has expanded in recent years, but non-neoplastic human brain tissue presents unique challenges due to its complexity. This study evaluated HALO and QuPath tau quantification performance in the hippocampus and mid-frontal gyrus across various tauopathies. Percent positivity emerged as the most reliable measure, showing strong correlations with Braak stages and CERAD scores, outperforming object and optical densities. QuPath demonstrated superior correlations with Braak stages, while HALO excelled in aligning with CERAD scoring. However, HALO's optical density was less consistent. Paired t-tests revealed significant differences in object and optical densities between platforms, though percent positivity was consistent across both. QuPath's threshold-based object density showed similar agreement with manual counts compared to HALO's AI-dependent approach (all ρ > 0.70). Reanalysis of QuPath further improved its agreement with manual measurements and correlations with Braak and CERAD scores (all ρ > 0.70). HALO offers a user-friendly interface and excels in certain metrics but is hindered by frequent software malfunctions and more limited flexibility. In contrast, QuPath's customizable workflows and superior performance in Braak staging make it more suitable for advanced and larger-scale analyses. Overall, our study highlights the strengths and limitations of these platforms, helping guide their application in neuropathology.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014920","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}
Ramada R Khaswaneh, Ejlal Abu-El-Rub, Ayman Alzu'bi, Rawan Almazari, Amneh Alrabie, Fatimah A Almahasneh, Amani Kasasbeh, Heba F Ai-Jariri, Ayman Mustafa
{"title":"Combining dopamine and vitamin E enhances the differentiation to cholinergic neurons of mesenchymal stem cells.","authors":"Ramada R Khaswaneh, Ejlal Abu-El-Rub, Ayman Alzu'bi, Rawan Almazari, Amneh Alrabie, Fatimah A Almahasneh, Amani Kasasbeh, Heba F Ai-Jariri, Ayman Mustafa","doi":"10.1093/jnen/nlaf025","DOIUrl":"https://doi.org/10.1093/jnen/nlaf025","url":null,"abstract":"<p><p>Recent research indicates that mesenchymal stem cells (MSCs) can transdifferentiate into neuron-like cells under specific conditions, offering promise for neuronal regeneration. However, challenges remain in optimizing differentiation protocols to generate specific neuron types. This study explores the impact of supplementing neuronal induction media with dopamine and vitamin E to guide MSCs toward specific neuronal subtypes. Human adipose-MSCs were utilized to investigate neuronal differentiation. The cells were cultured in induction media supplemented with 2 concentrations of dopamine (2.5 and 5 µM) and vitamin E (12.5 and 25 µM). Immunostaining and western blot analysis were employed to assess the sequential expression of neuronal markers associated with various stages of maturation and development. These markers included Nestin, MAP2, NeuN, TBR1, SATB2, DAT, DBH, and CHAT. The results demonstrate, for the first time, that supplementing neuronal induction media with dopamine and vitamin E significantly enhances and accelerates the differentiation of MSCs into neuronal cells. Furthermore, the findings suggest that the induced cells are predominantly reprogrammed toward a cholinergic neuronal lineage. For MSCs, our study reveals that the addition of dopamine and vitamin E reprograms MSCs mainly toward cholinergic neurons, suggesting promising approaches for treating neurodegenerative disorders.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023273","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}
Phuong Nguyen, Raquel T Yokoda, Quazi Hossain, Joshua B Bederson, Timothy E Richardson
{"title":"Solitary fibrous tumor-meningioma collision tumor with 18 years of follow-up.","authors":"Phuong Nguyen, Raquel T Yokoda, Quazi Hossain, Joshua B Bederson, Timothy E Richardson","doi":"10.1093/jnen/nlaf037","DOIUrl":"https://doi.org/10.1093/jnen/nlaf037","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026295","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}
Stuart D Harper, Travis Perryman, Lindsey A Dudley, Ashna S Prabhu, Amani Carson, Alondra Delgadillo, Eliana S Oduro, Othneil Sparks, Aidan Gor, Shivani Baisiwala, Ting Zhang, Fausto Rodriguez, Kunal S Patel
{"title":"Molecular characterization of benign intracranial glioependymal and arachnoid cysts suggest heterogeneous mechanisms of action.","authors":"Stuart D Harper, Travis Perryman, Lindsey A Dudley, Ashna S Prabhu, Amani Carson, Alondra Delgadillo, Eliana S Oduro, Othneil Sparks, Aidan Gor, Shivani Baisiwala, Ting Zhang, Fausto Rodriguez, Kunal S Patel","doi":"10.1093/jnen/nlaf029","DOIUrl":"https://doi.org/10.1093/jnen/nlaf029","url":null,"abstract":"<p><p>Benign-appearing intracranial cysts may become symptomatic due to mass effect and require surgical treatment. Mechanisms underlying cyst formation and growth remain poorly understood. This study identified 16 patients who underwent surgical treatment for benign intracranial cysts. Cyst wall pathologic samples (n = 8) were characterized as arachnoid or glioependymal cysts using H&E and immunofluorescence staining. Five samples (62.5%) were found to be glioependymal while three (37.5%) were arachnoid cysts. Cyst fluid examined in 4 cases resembled cerebrospinal fluid (CSF) and showed no significant differences in composition between pathological subtypes. Single-cell sequencing and RNA expression profile comparisons between glioependymal and arachnoid cysts revealed distinct cellular profiles. Analyses of the innermost cell layer (ependymal cells versus arachnoid cells) suggested differing mechanisms of pathogenesis. Glioependymal cysts harbored upregulated expression of sodium transporters and aquaporin channels, which suggests possible CSF-like fluid production whereas arachnoid cysts may be associated with mechanical fluid accumulation. Thus, intracranial cysts represent multiple unique pathologic entities with differing cell types and RNA expression profiles. Further study into mechanisms of glioependymal cyst formation may allow for targeted interventions to reduce fluid production and avoid surgery.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803468","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":"Correction to: PTEN Blocking Stimulates Corticospinal and Raphespinal Axonal Regeneration and Promotes Functional Recovery After Spinal Cord Injury.","authors":"","doi":"10.1093/jnen/nlaf027","DOIUrl":"https://doi.org/10.1093/jnen/nlaf027","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811644","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}
Christie G Turin, Timothy H Ung, B K Kleinschmidt-DeMasters
{"title":"TBX19/SF1 co-expressing pituitary neuroendocrine tumor/pituitary adenomas add to the lineage infidelity.","authors":"Christie G Turin, Timothy H Ung, B K Kleinschmidt-DeMasters","doi":"10.1093/jnen/nlaf028","DOIUrl":"https://doi.org/10.1093/jnen/nlaf028","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803470","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}