Free neuropathology最新文献

{"title":"Mesial temporal lobe epilepsy and hippocampal sclerosis associated with <i>BRAFV600E</i> mutant neurons in the Cornu Ammonis: an uncertain pathogenesis and a diagnostic challenge.","authors":"Samir Alsalek, Alexander S Himstead, Scott Self, Gianna M Fote, Sumeet Vadera, Edwin S Monuki, Mari Perez-Rosendahl, William H Yong","doi":"10.17879/freeneuropathology-2024-5269","DOIUrl":"10.17879/freeneuropathology-2024-5269","url":null,"abstract":"<p><p>Mesial temporal lobe epilepsy (MTLE) is a common cause of seizures, and hippocampal sclerosis (HS) is the predominant subtype. <i>BRAFV600E</i> mutations in MTLE-HS have only been reported infrequently. Herein, we illustrate the neurologic, radiological, and histopathological details of a patient with MTLE-HS and <i>BRAFV600E</i> mutant neurons. A 31-year-old male with medically refractory epilepsy presented with magnetic resonance imaging (MRI) and electroencephalography (EEG) findings typical of mesial temporal sclerosis without a mass lesion. The surgical specimens showed ILAE Type 1 HS with neurons immunopositive for BRAFV600E mutant protein distributed along the Cornu Ammonis (CA) curvature. Instead of the normal mostly perpendicular orientation of pyramidal neurons relative to the hippocampal surface, the <i>BRAF</i> mutant neurons were often oriented in a parallel manner. On CD34 immunostaining, sparse clusters or nodules of CD34+ stellate cells and single immunopositive stellate cells were identified. BRAFV600E or CD34 immunopositive cells were less than 1 % of total cells. The patient responded well to surgery with no further seizures after 2 years and occasional auras. Hippocampal <i>BRAF</i> mutant non-expansive lesion (HBNL) has been used to describe such lesions with preserved cytoarchitecture and without overt tumor mass. Others may argue for the dual pathology of HS with early ganglioglioma. Whether pre-neoplastic lesions or early tumors, these cases are important for understanding early glioneuronal tumorigenesis and suggest that BRAFV600E studies should be routinely performed on MTLE-HS cases in the setting of clinical trials. With next-generation sequencing, a <i>FANCL</i> deletion was detected in almost half of the alleles in our case, suggesting that many of the histologically normal-appearing cells of the hippocampus contain this alteration. <i>FANCL</i> mutations can result in cytogenetic anomalies and defective DNA repair and therefore may underlie the development of a low frequency <i>BRAF</i> alteration.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"18"},"PeriodicalIF":0.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082815","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":"Cell-in-cell phenomena of intracellular neutrophils in a recurrent pleomorphic xanthoastrocytoma.","authors":"Gianna M Fote, Kamran Urgun, Jordan Davies, Alexander S Himstead, Kevin Gramajo-Aponte, Alexander Lopez, Frank P K Hsu, William H Yong","doi":"10.17879/freeneuropathology-2024-5341","DOIUrl":"10.17879/freeneuropathology-2024-5341","url":null,"abstract":"<p><p>We describe a case of a young patient with a recurrent pleomorphic xanthoastrocytoma (PXA) showing unusual cell-in-cell (CiC) phenomena. We observed mostly viable but also necrotic neutrophils engulfed within tumor cells. The recurrent tumor was immunopositive for BRAFV600E mutant protein and showed CDKN2 homozygous deletions typical of PXA. Both genetic alterations were also reported in the original primary tumor. Unlike the original tumor that was GFAP and Olig-2 immunopositive, the recurrent neoplasm was largely negative for GFAP and Olig-2 suggesting dedifferentiation. The large malignant cells that contained the neutrophils were negative for histiocytic and lymphohematopoietic markers. Whereas CDKN2 homozygous deletion is common in PXA, its presence is rare in histiocytic neoplasms. Both reactive astrocytes and glial neoplasms very rarely may engulf neutrophils in a process resembling emperipolesis or cellular cannibalism. Future work may clarify which type of CiC pathway is involved.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"17"},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977356","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":"Fast-track neuropathological screening for neurodegenerative diseases.","authors":"Benjamin Englert, Sigrun Roeber, Thomas Arzberger, Viktoria Ruf, Otto Windl, Jochen Herms","doi":"10.17879/freeneuropathology-2024-5643","DOIUrl":"10.17879/freeneuropathology-2024-5643","url":null,"abstract":"<p><p><b>Background:</b> The <i>postmortem</i> diagnostic of individuals having suffered presumptive neurodegenerative disease comprises exclusion of a prion disease, extensive brain sampling and histopathological evaluation, which are resource-intensive and time consuming. To exclude prion disease and to achieve prompt accurate preliminary diagnosis, we developed a fast-track procedure for the histopathological assessment of brains from patients with suspected neurodegenerative disease. <b>Methods:</b> Based on the screening of two brain regions (frontal cortex and cerebellum) with H&E and six immunohistochemical stainings in 133 brain donors, a main histopathological diagnosis was established and compared to the final diagnosis made after a full histopathological work-up according to our brain bank standard procedure. <b>Results:</b> In over 96 % of cases there was a concordance between the fast-track and the final main neuropathological diagnosis. A prion disease was identified in four cases without prior clinical suspicion of a prion infection. <b>Conclusion:</b> The fast-track screening approach relying on two defined, easily accessible brain regions is sufficient to obtain a reliable tentative main diagnosis in individuals with neurodegenerative disease and thus allows for a prompt feedback to the physicians. However, a more thorough histological work-up taking into account the clinical history and the working diagnosis from fast-track screening is necessary for accurate staging and for assessment of co-pathologies.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11309573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908533","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":"An optimized filter trap assay for detecting recombinant authentic tau fibrils.","authors":"Allison R Balaj, Thomas L Rothstein, Hiroaki Kaku","doi":"10.17879/freeneuropathology-2024-5497","DOIUrl":"10.17879/freeneuropathology-2024-5497","url":null,"abstract":"<p><p>The development and optimization of the Filter Trap Assay (FTA) for the detection of authentic tau fibrils <i>in vitro</i> mark a pivotal advancement in the realm of tauopathy research, particularly by addressing the limitations of using polyanion-induced tau fibrils, which structurally differ from those isolated from tauopathy patients. Recently it has been shown that truncated tau fragment (297-391), also termed dGAE, can form authentic tau fibrils in the absence of polyanions. This study introduces a refined protocol that reliably detects authentic tau fibrils in a physiologically relevant framework, utilizing nitrocellulose membranes to achieve heightened sensitivity. Our investigation highlights the superior efficacy of sarkosyl, an anionic surfactant traditionally used to prepare protein lysates from brains and cultured neurons, in preserving the aggregated state of tau dGAE fibrils <i>in vitro</i>, underscoring its potential for further exploratory studies. By offering a user-friendly and economically feasible approach, this technique enables a broad range of laboratories to measure the presence of authentic tau fibrils. This methodological enhancement propels our understanding of tauopathies forward and bridges the gap between basic research and advanced structural analyses, enriching the scientific community's methodologies for studying neurodegenerative disorders.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899101","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":"Stem cell-associated transcription factors in non-functioning pituitary neuroendocrine tumours.","authors":"Kristin Astrid Øystese, Nicoleta Cristina Olarescu, Cecilia Lindskog, Fabjola Xheka, Jon Berg-Johnsen, Jens Petter Berg, Jens Bollerslev, Olivera Casar-Borota","doi":"10.17879/freeneuropathology-2024-5396","DOIUrl":"10.17879/freeneuropathology-2024-5396","url":null,"abstract":"<p><p><b>Background</b>: Cells with stem cell features have been described in pituitary neuroendocrine tumours (PitNETs). Transcription factors SOX2 and SOX9 are stem cell-associated markers while the pituitary progenitor marker PROP1 is involved in anterior pituitary development. We characterised the presence of these markers known to be present in the human pituitary in non-functioning (NF) PitNETs. <b>Methods</b>: We investigated the pituitary transcription factors SOX2, SOX9 and PROP1 by immunohistochemistry (IHC) (N = 125) and RT-qPCR (N = 78) in a retrospective cohort of clinically NF-PitNETs. The markers were scored based on the percentage of immunolabeled cells. IHC staining scores were compared to reintervention rates for the whole cohort, and to expression of FSH, LH or ER in gonadotroph NF-PitNETs. <b>Results</b>: Most tumours showed no or few cells positive for SOX2, SOX9 and PROP1. More patients with SOX2-negative tumours went through reintervention (40 % vs 19 %, p = 0.03). SOX2, SOX9 and PROP1 staining correlated positively to each other (SOX2 and SOX9 r_s = 0.666, SOX2 and PROP1 r_s = 0.704, SOX9 and PROP1 r_s = 0.570, and p < 0.001 for all). In gonadotroph NF-PitNETs, staining for SOX2 and PROP1 was positively associated to FSHβ staining (p < 0.001 for both). Staining for SOX2, SOX9 and PROP1 was positively associated with gene expression of Estrogen Receptor 1 (ESR1) (p < 0.001, p = 0.004 and p < 0.001) and IHC staining for ERα (p = 0.001, p = 0.03 and p = 0.05, respectively). <b>Conclusion</b>: SOX2, SOX9 and PROP1 were present at low levels in NF-PitNETs. Absence of SOX2 staining was associated with a higher reintervention rate. The stem cell markers correlated positively with markers of gonadotroph differentiation in gonadotroph NF-PitNETs. SOX2 and SOX9 were frequently coexpressed and showed positivity in intratumoural cells with epithelial features, however without coexpression of pituitary transcription factors.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11155689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141285563","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":"The presence of shrunken neurons with pyknotic nuclei in the dentate nucleus is a common postmortem change associated with autolysis of the cerebellar granular cell layer.","authors":"Bilge Dundar, Busranur Agac, Eyas Alzayadneh, Randy Tashjian, Kyle S Conway","doi":"10.17879/freeneuropathology-2024-5398","DOIUrl":"10.17879/freeneuropathology-2024-5398","url":null,"abstract":"","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11129276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158918","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":"Malignant glioma in L-2-Hydroxyglutaric Aciduria: thorough molecular characterization of a case and literature review.","authors":"Fleur Cordier, Pieter Wesseling, Bastiaan B J Tops, Lennart Kester, Pim J French, Martin van den Bent, Felix Hinz, Eleonora Aronica, K Mariam Slot, Floor Abbink, Marjo S van der Knaap, Mariëtte E G Kranendonk","doi":"10.17879/freeneuropathology-2024-5377","DOIUrl":"10.17879/freeneuropathology-2024-5377","url":null,"abstract":"<p><p>L-2-hydroxyglutaric aciduria (L-2-HGA) is a rare neurometabolic disorder characterized by accumulation of L2-hydroxyglutarate (L-2-HG) due to mutations in the <i>L2HGDH</i> gene. L-2-HGA patients have a significantly increased lifetime risk of central nervous system (CNS) tumors. Here, we present a 16-year-old girl with L-2-HGA who developed a tumor in the right cerebral hemisphere, which was discovered after left-sided neurological deficits of the patient. Histologically, the tumor had a high-grade diffuse glioma phenotype. DNA sequencing revealed the inactivating homozygous germline <i>L2HGDH</i> mutation as well as inactivating mutations in <i>TP53</i>, <i>BCOR</i> and <i>NF1</i>. Genome-wide DNA-methylation analysis was unable to classify the tumor with high confidence. More detailed analysis revealed that this tumor clustered amongst IDH-wildtype gliomas by methylation profiling and did not show the glioma CpG island methylator phenotype (G-CIMP) in contrast to IDH-mutant diffuse gliomas with accumulated levels of D-2-HG, the stereoisomer of L-2-HD. These findings were against all our expectations given the inhibitory potential of 2-HG on DNA-demethylation enzymes. Our final integrated histomolecular diagnosis of the tumor was diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype. Due to rapid tumor progression the patient died nine months after initial diagnosis. In this manuscript, we provide extensive molecular characterization of the tumor as well as a literature review focusing on oncogenetic considerations of L-2-HGA-associated CNS tumors.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11075094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878086","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":"Brainstem inflammation in sudden unexpected death in infancy and childhood (SIDS/SUDC).","authors":"Herbert Budka, Daniele U Risser, Fabio C Monticelli","doi":"10.17879/freeneuropathology-2024-5479","DOIUrl":"10.17879/freeneuropathology-2024-5479","url":null,"abstract":"","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11075525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878085","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":"Fluid preservation in brain banking: a review.","authors":"Andrew T McKenzie, Oge Nnadi, Kat D Slagell, Emma L Thorn, Kurt Farrell, John F Crary","doi":"10.17879/freeneuropathology-2024-5373","DOIUrl":"10.17879/freeneuropathology-2024-5373","url":null,"abstract":"<p><p>Fluid preservation is nearly universally used in brain banking to store fixed tissue specimens for future research applications. However, the effects of long-term immersion on neural circuitry and biomolecules are not well characterized. As a result, there is a need to synthesize studies investigating fluid preservation of brain tissue. We searched PubMed and other databases to identify studies measuring the effects of fluid preservation in nervous system tissue. We categorized studies based on the fluid preservative used: formaldehyde solutions, buffer solutions, alcohol solutions, storage after tissue clearing, and cryoprotectant solutions. We identified 91 studies containing 197 independent observations of the effects of long-term storage on cellular morphology. Most studies did not report any significant alterations due to long-term storage. When present, the most frequent alteration was decreased antigenicity, commonly attributed to progressive crosslinking by aldehydes that renders biomolecules increasingly inaccessible over time. To build a mechanistic understanding, we discuss biochemical aspects of long-term fluid preservation. A subset of lipids appears to be chemical altered or extracted over time due to incomplete retention in the crosslinked gel. Alternative storage fluids mitigate the problem of antigen masking but have not been extensively characterized and may have other downsides. We also compare fluid preservation to cryopreservation, paraffin embedding, and resin embedding. Overall, existing evidence suggests that fluid preservation provides maintenance of neural architecture for decades, including precise structural details. However, to avoid the well-established problem of overfixation caused by storage in high concentration formaldehyde solutions, fluid preservation procedures can use an initial fixation step followed by an alternative long-term storage fluid. Further research is warranted on optimizing protocols and characterizing the generalizability of the storage artifacts that have been identified.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11058410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856068","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":"A hobby neuropathologist from Far East resides in Western Europe.","authors":"Akira Hori","doi":"10.17879/freeneuropathology-2024-5275","DOIUrl":"10.17879/freeneuropathology-2024-5275","url":null,"abstract":"","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"4 ","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11033579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873000","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}