Free neuropathology最新文献

{"title":"Heterogeneity of DNA methylation profiles and copy number alterations in 10782 adult-type glioblastomas, IDH-wildtype.","authors":"David E Reuss, Daniel Schrimpf, Asan Cherkezov, Abigail K Suwala, Tereza Lausová, Matija Snuderl, David Capper, Martin Sill, David T W Jones, Stefan M Pfister, Felix Sahm, Andreas von Deimling","doi":"10.17879/freeneuropathology-2024-5345","DOIUrl":"10.17879/freeneuropathology-2024-5345","url":null,"abstract":"<p><p>The morphological patterns leading to the diagnosis of glioblastoma may also commonly be observed in several other distinct tumor entities, which can result in a mixed bag of tumors subsumed under this diagnosis. The 2021 WHO Classification of CNS Tumors has separated several of these entities from the diagnosis of glioblastoma, IDH-wildtype. This study determines the DNA methylation classes most likely receiving the diagnosis glioblastoma, IDH wildtype according to the definition by the WHO 2021 Classification and provides comparative copy number analyses. We identified 10782 methylome datasets uploaded to the web page www.molecularneuropathology.org with a calibrated score of ≥0.9 by the Heidelberg Brain Tumor Classifier version v12.8. These methylation classes were characterized by the diagnosis glioblastoma being the most frequent classification encountered in each of the classes according to the WHO 2021 definition. Further, methylation classes selected for this study predominantly contained adult patients. Unsupervised clustering confirmed the presence of nine methylation classes containing tumors most likely receiving the diagnosis glioblastoma, IDH-wildtype according to the WHO 2021 definition. Copy number analysis and a focus on genes with typical numerical alterations in glioblastoma revealed clear differences between the nine methylation classes. Although great progress in diagnostic precision has been achieved over the last decade, our data clearly demonstrate that glioblastoma, IDH-wildtype still is a heterogeneous group in need of further stratification.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10964111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropathology and epilepsy surgery - 2024 update.","authors":"Ingmar Blümcke","doi":"10.17879/freeneuropathology-2024-5347","DOIUrl":"10.17879/freeneuropathology-2024-5347","url":null,"abstract":"<p><p>Neuropathology-based studies in neurosurgically resected brain tissue obtained from carefully examined patients with focal epilepsies remain a treasure box for excellent insights into human neuroscience, including avenues to better understand the neurobiology of human brain organization and neuronal hyperexcitability at the cellular level including glio-neuronal interaction. It also allows to translate results from animal models in order to develop personalized treatment strategies in the near future. A nice example of this is the discovery of a new disease entity in 2017, termed mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy or MOGHE, in the frontal lobe of young children with intractable seizures. In 2021, a brain somatic missense mutation of the galactose transporter SLC35A2 leading to altered glycosylation of lipoproteins in the Golgi apparatus was detected in 50 % of MOGHE samples. In 2023, the first clinical trial evaluated galactose supplementation in patients with histopathologically confirmed MOGHE carrying brain somatic <i>SLC35A2</i> mutations that were not seizure free after surgery. The promising results of this pilot trial are an example of personalized medicine in the arena of epileptology. Besides this, neuropathological studies of epilepsy samples have revealed many other fascinating results for the main disease categories in focal epilepsies, such as the first deep-learning based classifier for Focal Cortical Dysplasia, or the genomic landscape of cortical malformations showing new candidate genes such as <i>PTPN11</i>, which is associated with ganglioglioma and adverse clinical outcome. This update will also ask why common pathogenic variants accumulate in certain brain regions, e.g., <i>MTOR</i> in the frontal lobe, and <i>BRAF</i> in the temporal lobe. Finally, I will highlight the ongoing discussion addressing commonalities between temporal lobe epilepsy and Alzheimer's disease, the impact of adult neurogenesis and gliogenesis for the initiation and progression of temporal lobe seizures in the human brain as well as the immunopathogenesis of glutamic acid decarboxylase antibody associated temporal lobe epilepsy as a meaningful disease entity. This review will update the reader on some of these fascinating publications from 2022 and 2023 which were selected carefully, yet subjectively, by the author.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10964794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Searching for a cut-off point for p53 immunohistochemistry as evidence of TP53 mutations.","authors":"Ilay Caliskan, Rufei Lu, Cristine Szu Lyn Ding, Francineide Sadala de Souza, Arie Perry, Tarik Tihan","doi":"10.17879/freeneuropathology-2024-5337","DOIUrl":"10.17879/freeneuropathology-2024-5337","url":null,"abstract":"","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10929731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140112386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIV and COVID-19: two pandemics with significant (but different) central nervous system complications.","authors":"Shino Magaki, Ting Zhang, Karam Han, Mirbaha Hilda, William H Yong, Cristian Achim, Gregory Fishbein, Michael C Fishbein, Omai Garner, Noriko Salamon, Christopher K Williams, Miguel A Valdes-Sueiras, Jeffrey J Hsu, Theodoros Kelesidis, Glenn E Mathisen, Helen Lavretsky, Elyse J Singer, Harry V Vinters","doi":"10.17879/freeneuropathology-2024-5343","DOIUrl":"10.17879/freeneuropathology-2024-5343","url":null,"abstract":"<p><p>Human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause significant neurologic disease. Central nervous system (CNS) involvement of HIV has been extensively studied, with well-documented invasion of HIV into the brain in the initial stage of infection, while the acute effects of SARS-CoV-2 in the brain are unclear. Neuropathologic features of active HIV infection in the brain are well characterized whereas neuropathologic findings in acute COVID-19 are largely non-specific. On the other hand, neuropathologic substrates of chronic dysfunction in both infections, as HIV-associated neurocognitive disorders (HAND) and post-COVID conditions (PCC)/long COVID are unknown. Thus far, neuropathologic studies on patients with HAND in the era of combined antiretroviral therapy have been inconclusive, and autopsy studies on patients diagnosed with PCC have yet to be published. Further longitudinal, multidisciplinary studies on patients with HAND and PCC and neuropathologic studies in comparison to controls are warranted to help elucidate the mechanisms of CNS dysfunction in both conditions.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10925920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140102968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blocking TGF-β- and Epithelial-to-Mesenchymal Transition (EMT)-mediated activation of vessel-associated mural cells in glioblastoma impacts tumor angiogenesis.","authors":"Luisa Merk, Katja Regel, Hermann Eckhardt, Marietheres Evers, Ali El-Ayoubi, Michel Mittelbronn, Marcel Krüger, Jean-Jacques Gérardy, Andreas F Mack, Ulrike Naumann","doi":"10.17879/freeneuropathology-2024-5188","DOIUrl":"10.17879/freeneuropathology-2024-5188","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. GBM displays excessive and unfunctional vascularization which may, among others, be a reason for its devastating prognosis. Pericytes have been identified as the major component of the irregular vessel structure in GBM. <i>In vitro</i> data suggest an epithelial-to-mesenchymal transition (EMT)-like activation of glioma-associated pericytes, stimulated by GBM-secreted TGF-β, to be involved in the formation of a chaotic and dysfunctional tumor vasculature. This study investigated whether TGF-β impacts the function of vessel associated mural cells (VAMCs) <i>in vivo</i> via the induction of the EMT transcription factor SLUG and whether this is associated with the development of GBM-associated vascular abnormalities. Upon preventing the TGF-β-/SLUG-mediated EMT induction in VAMCs, the number of PDGFRβ and αSMA positive cells was significantly reduced, regardless of whether TGF-β secretion by GBM cells was blocked or whether SLUG was specifically knocked out in VAMCs. The reduced amount of PDGFRβ⁺ or αSMA⁺ cells observed under those conditions correlated with a lower vessel density and fewer vascular abnormalities. Our data provide evidence that the SLUG-mediated modulation of VAMC activity is induced by GBM-secreted TGF-β¬ and that activated VAMCs are key contributors in neo-angiogenic processes. We suggest that a pathologically altered activation of GA-Peris in the tumor microenvironment is responsible for the unstructured tumor vasculature. There is emerging evidence that vessel normalization alleviates tumor hypoxia, reduces tumor-associated edema and improves drug delivery. Therefore, avoiding the generation of an unstructured and non-functional tumor vasculature during tumor recurrence might be a promising treatment approach for GBM and identifies pericytes as a potential novel therapeutic target.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10919159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140061441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular activation patterns of CD10+ fibro-adipogenic progenitors across acquired disease states in human skeletal muscle biopsies.","authors":"Peter W Schutz, Simon Cheung, Lin Yi, Fabio M V Rossi","doi":"10.17879/freeneuropathology-2024-5162","DOIUrl":"10.17879/freeneuropathology-2024-5162","url":null,"abstract":"<p><p><b>Background:</b> Fibro-adipogenic progenitors (FAP) are muscle resident mesenchymal stem cells pivotal for regulation of myofiber repair. Experimental results show in addition involvement in a range of other pathological conditions and potential for pharmacological intervention. FAP histopathology in human muscle biopsies is largely unknown, but has potential to inform translational research. <b>Methods:</b> CD10+ FAPs in 32 archival muscle biopsies from 8 groups (normal, dermatomyositis, inclusion body myositis (IBM), anti-synthetase syndrome, immune-mediated necrotizing myopathy (IMNM), denervation, type 2 atrophy, rhabdomyolysis) were visualized by CD10 immunohistochemistry and their histology compared. Groups are compared by semi-quantitative scoring. <b>Results:</b> Histological activation of endomysial CD10+ FAPs includes prominent expansion of a network of cell processes surrounding muscle fibers, as well as endomysial cell clusters evidencing proliferation. Prominence of periarteriolar processes is a notable feature in some pathologies. FAP activation is often associated with fiber degeneration/regeneration, foci of inflammation, and denervation in keeping with experimental results. Type 2 atrophy shows no evidence of FAP activation. Dermatomyositis and anti-synthetase syndrome associated myositis demonstrate diffuse activation. <b>Conclusion:</b> Assessment of CD10+ FAP activation is routinely possible using CD10 immunohistochemistry and demonstrates several patterns in keeping with preclinical results. Prominent expansion of FAP processes surrounding myofibers suggests enhanced interaction between myofiber/basement membranes and FAPs during activation. The presence of diffuse FAP activation in dermatomyositis biopsies unrelated to fiber repair raises the possibility of FAP activation as part of the autoimmune process. Future diagnostic applications, clinical significance and therapeutic potential remain to be elucidated.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10865694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139736871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pituitary adenoma classification: Tools to improve the current system.","authors":"William Charles McDonald","doi":"10.17879/freeneuropathology-2024-5226","DOIUrl":"10.17879/freeneuropathology-2024-5226","url":null,"abstract":"<p><p>The World Health Organization classification of pituitary tumors provides a framework for pathologists and researchers to classify pituitary adenomas. From the perspective of a practicing pathologist, this classification can be improved by pooling immunohistochemical data in a more standardized way, and by deliberately distinguishing features that assist in classification from those that do not. This article illustrates one general workflow to examine classification features consisting of immunohistochemical stains for anterior pituitary tumors, in order to promote debate and advance an evidence-based framework for classification.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10782462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139426144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep RNA sequencing of muscle tissue reveals absence of viral signatures in dermatomyositis.","authors":"Victor M Corman, Corinna Preusse, Julia Melchert, Olivier Benveniste, Randi Koll, Hans-Hilmar Goebel, Terry C Jones, Christian Drosten, Ulrike Schara-Schmidt, Sarah Leonard-Louis, Werner Stenzel, Josefine Radke","doi":"10.17879/freeneuropathology-2024-5149","DOIUrl":"10.17879/freeneuropathology-2024-5149","url":null,"abstract":"<p><p><b>Objective</b>: To explore a possible connection between active viral infections and manifestation of dermatomyositis (DM). <b>Methods:</b> Skeletal muscle biopsies were analyzed from patients diagnosed with juvenile (n=10) and adult (n=12) DM. Adult DM patients harbored autoantibodies against either TIF-1γ (n=7) or MDA5 (n=5). Additionally, we investigated skeletal muscle biopsies from non-diseased controls (NDC, n=5). We used an unbiased high-throughput RNA sequencing (HTS) approach to detect viral sequences. To further increase sequencing depth, a host depletion approach was applied. <b>Results</b>: In this observational study, no relevant viral sequences were detected either by native sequencing or after host depletion. The absence of detectable viral sequences makes an active viral infection of the muscle tissue unlikely to be the cause of DM in our cohorts. <b>Discussion:</b> Type I interferons (IFN) play a major role in the pathogenesis of both juvenile and adult DM. The IFN response is remarkably conserved between DM subtypes classified by specific autoantibodies. Certain acute viral infections are accompanied by a prominent type I IFN response involving similar downstream mechanisms as in DM. Aiming to elucidate the pathogenesis of DM in skeletal muscle tissue, we used deep RNA sequencing and a host depletion approach to detect possible causative viruses.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10774810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139418753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Considering the myelin-centric hypothesis: insights from Budka's historical adrenomyeloneuropathy case report.","authors":"Ettore Salsano, Chiara Benzoni","doi":"10.17879/freeneuropathology-2023-5218","DOIUrl":"10.17879/freeneuropathology-2023-5218","url":null,"abstract":"","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"23"},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10740879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adrenomyeloneuropathy (AMN): myelinopathy or axonopathy?: Comment on: Considering the myelin-centric hypothesis: insights from Budka's historical adrenomyeloneuropathy case report by E. Salsano and C. Benzoni.","authors":"Herbert Budka","doi":"10.17879/freeneuropathology-2023-5227","DOIUrl":"10.17879/freeneuropathology-2023-5227","url":null,"abstract":"","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"24"},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10734313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138833351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}