Brain Pathology最新文献

{"title":"Society News","authors":"","doi":"10.1111/bpa.13308","DOIUrl":"https://doi.org/10.1111/bpa.13308","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13308","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142447543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"40-Year-old man with two asynchronous spinal cord tumors","authors":"Maximilian Bschorer, Matthias Dottermusch, Jakob Matschke, Jens Gempt, Ulrich Schüller, Malte Mohme","doi":"10.1111/bpa.13309","DOIUrl":"10.1111/bpa.13309","url":null,"abstract":"<p>A 38-year-old individual presented with intermittent bladder dysfunction, radicular pain, and mild foot elevator paresis. After an emergency lumbar MRI revealed a vertebral disc herniation at the L5/S1 level, an emergency sequestrectomy was performed. Although the radicular pain resolved postoperatively, the patient's bladder voiding dysfunction worsened. Further MRI imaging revealed a contrast-enhancing intramedullary lesion at the TH11/TH12 spinal levels (Figure 1A).</p><p>The patient was transferred to the neurosurgical department for further treatment, and urgent surgery was performed with continuous intraoperative neurophysiological monitoring. Histopathological analysis was conducted and subsequent DNA methylation analysis confirmed the histological diagnosis. The patient did not undergo genetic testing for neurofibromatosis (NF), as he did not exhibit any other typical features or tumors associated with NF.</p><p>Postoperative paraparesis and bladder dysfunction were promptly resolved in neurological rehabilitation, resulting in a McCormick score of one. Three years later, the patient presented with new radiculopathy in both legs accompanied and hypesthesia. MRI showed a new contrast-enhancing lesion at L2/L3, which was located at a distance from the previous lesion (Figure 1B). The patient underwent surgery for this symptomatic lesion. The histopathological and methylation analysis revealed a distinct diagnosis, when compared to the histological examination of the initial tumor. Postoperative imaging showed no residual tumor, and there were no other central nervous system (CNS) manifestations of the tumor. The patient's rapid recovery from neurological symptoms allowed for discharge to ambulatory service.</p><p>Histological comparison of the first and second tumor revealed distinctive features. The first tumor was characterized by isomorphic glial cells with round nuclei within a delicate fibrillary matrix, as observed in H&E staining (Figure 2, Box 1). The tumor cells showed clear expression of glial fibrillary acidic protein (GFAP), but not OLIG2 or NMYC. The Ki67 labeling index was below 5% of the tumor cell nuclei. Zones without nuclei around blood vessels, known as perivascular pseudorosettes, were also present.</p><p>The second tumor was characterized by more spindled tumor cells within a coarse myxoid glial matrix, indicative of a divergent histological diagnosis. The cell nuclei were oval to elongated with slightly loosened nuclear chromatin. Similar to the first tumor, strong GFAP immunostaining was observed. The second tumor was distinctively marked by nuclear expression of HOXB1, absent in the first tumor.</p><p>For both samples, DNA methylation data were obtained using the Illumina Human MethylationEPIC (850 k) array bead chips. The classification of brain tumors based on DNA methylation was performed using the publicly available “classifier” tool, version v12.8 (www.molecularneuropathology.org/mnp). The epigenetic anal","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13309","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 55-year-old man with a cerebral mass","authors":"Serena Ammendola, Giuseppe Kenneth Ricciardi, Valeria Barresi","doi":"10.1111/bpa.13310","DOIUrl":"10.1111/bpa.13310","url":null,"abstract":"<p>A 55-year-old man presented with recent onset of dizziness and left lower limb weakness. Magnetic resonance imaging revealed a relatively circumscribed mass in the left frontal lobe extending to the corpus callosum and contralateral hemisphere, with conspicuous perilesional edema and contrast enhancement (Figure 1). A whole-body computerized tomography (CT) scan did not reveal any other lesions. The patient underwent partial excision of the mass. F-18 fluorodeoxyglucose–positron emission tomography (PET) imaging demonstrated hypermetabolism in the residual brain mass, but no evidence of any lesion outside the central nervous system.</p><p>Microscopic examination revealed a hypercellular neoplasm mainly composed of large cells exhibiting irregular or indented, frequently nucleolated, nuclei, and eosinophilic cytoplasm, and characterized by brisk mitotic activity (Figure 2A; Box 1) and necrosis. Additionally, scattered binucleated or multinucleated cells were observed (Figure 2A). Some neoplastic cells exhibited hemophagocytic activity, consisting of engulfment of fragmented neutrophils or red blood cells in the cytoplasm (Figure 2B), whereas others displayed a brown cytoplasmic pigment (Figure 2C). Perl's staining revealed the presence of iron deposits in these cells (Figure 2D). Immunohistochemistry showed that the tumor cells were diffusely positive for CD68 (Figure 2E), CD163 (Figure 2F), and CD45, and negative for CD3, CD20, CD30, ALK, Langerin (CD207), CD21, myeloperoxidase, CD34, CD117, HMB45, Melan-A, CKAE1-AE3, GFAP, and OLIG2. CD4 (Figure 2G) and S100 positivity was observed in some neoplastic cells (Figure 2). Ki-67 labeling index was 40%. Immuno-expression of BRAF p. V600E was absent. CD3 immunostaining revealed abundant infiltration of small lymphocytes (Figure 2H).</p><p>Histiocytic sarcoma (HS).</p><p>HS is an exceedingly rare and aggressive hematopoietic tumor that primarily affects the lymph nodes, skin, gastrointestinal tract, or soft tissues, and can occur in individuals of varying ages, ranging from infancy to older adulthood. Primary HS of the central nervous system (CNS) is extremely uncommon, with fewer than 40 cases reported in the English literature [<span>1</span>]. Herein we present an additional case, which was considered as primary HS of the CNS owing to the lack of localization outside the CNS on CT and PET scans. According to the World Health Organization classification of CNS tumors, HS is defined as a malignant proliferation of cells showing morphological and immunophenotypic features of histiocytes and no other lines of differentiation. Histologically, HS is characterized by large cells with irregular nucleolated nuclei and eosinophilic cytoplasm, and brisk mitotic activity. An infiltrate of lymphocytes surrounding tumor cells, along with the presence of large pleomorphic cells and CD45 positivity may suggest anaplastic large-cell lymphoma or diffuse large B-cell lymphoma. However, the absence of immunostaining ","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13310","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"hnRNP A1, hnRNP A2B1, and hnRNP K are dysregulated in tauopathies, but do not colocalize with tau pathology.","authors":"Tomas Kavanagh, Kaleah Balcomb, Diba Ahmadi Rastegar, Guinevere F Lourenco, Thomas Wisniewski, Glenda Halliday, Eleanor Drummond","doi":"10.1111/bpa.13305","DOIUrl":"https://doi.org/10.1111/bpa.13305","url":null,"abstract":"<p><p>Tau interacts with multiple heterogeneous nuclear ribonucleoproteins (hnRNPs)-a family of RNA binding proteins that regulate multiple known cellular functions, including mRNA splicing, mRNA transport, and translation regulation. We have previously demonstrated particularly significant interactions between phosphorylated tau and three hnRNPs (hnRNP A1, hnRNP A2B1, and hnRNP K). Although multiple hnRNPs have been previously implicated in tauopathies, knowledge of whether these hnRNPs colocalize with tau aggregates or show cellular mislocalization in disease is limited. Here, we performed a neuropathological study examining the colocalization between hnRNP A1, hnRNP A2B1, hnRNP K, and phosphorylated tau in two brain regions (hippocampus and frontal cortex) in six disease groups (Alzheimer's disease, mild cognitive impairment, progressive supranuclear palsy, corticobasal degeneration, Pick's disease, and controls). Contrary to expectations, hnRNP A1, hnRNP A2B1, and hnRNP K did not colocalize with AT8-immunoreactive phosphorylated tau pathology in any of the tauopathies examined. However, we did observe significant cellular mislocalization of hnRNP A1, hnRNP A2B1 and hnRNP K in tauopathies, with unique patterns of mislocalization observed for each hnRNP. These data point to broad dysregulation of hnRNP A1, A2B1 and K across tauopathies with implications for disease processes and RNA regulation.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13305"},"PeriodicalIF":5.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Posterior pituitary tumors and other rare entities involving the pituitary gland.","authors":"Federico Roncaroli, Caterina Giannini","doi":"10.1111/bpa.13307","DOIUrl":"https://doi.org/10.1111/bpa.13307","url":null,"abstract":"<p><p>Non-neuroendocrine tumors account for around 10% of all primary neoplasms of the sella. If meningiomas, craniopharyngiomas, and germ cell tumors are excluded, the remaining lesions include a broad spectrum of uncommon, benign, and aggressive, often diagnostically challenging lesions. This review aims to summarize the essential clinicopathological features of tumors of the posterior pituitary gland, infundibulum spectrum expressing thyroid transcription factor 1, and primary sellar atypical rhabdoid teratoid tumor, and provide the criteria for their diagnosis and management.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13307"},"PeriodicalIF":5.8,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 53-year-old woman with a 16-year history of epilepsy","authors":"Rong Ge, Chenning Shao, Lixia Lu, Li Wang, Can Peng","doi":"10.1111/bpa.13311","DOIUrl":"https://doi.org/10.1111/bpa.13311","url":null,"abstract":"<div>\u0000<h3><span>BOX 1. </span>Virtual glass slide</h3>\u0000<p>https://isn-slidearchive.org/?col=ISN&amp;fol=Archive&amp;file=BPA-24-04-CI-091.svs</p>\u0000</div>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"191 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DCC in the cerebral cortex is required for cognitive functions in mouse","authors":"Yun-Qing Hu, Wei-Tang Liu, Yong Wu, Zhi-Bin Hu, Yun-Chao Tao, Qiong Zhang, Jia-Yin Chen, Ming Li, Ling Hu, Yu-Qiang Ding","doi":"10.1111/bpa.13306","DOIUrl":"https://doi.org/10.1111/bpa.13306","url":null,"abstract":"Schizophrenia (SZ) is a highly heritable mental disorder, and genome-wide association studies have identified the association between <i>deleted in colorectal cancer</i> (<i>DCC</i>) and SZ. Previous study has shown a lowered expression of <i>DCC</i> in the cerebral cortex of SZ patient. In this study, we identified novel single nucleotide polymorphisms (SNPs) of <i>DCC</i> statistically correlated with SZ. Based on these, we generated DCC conditional knockout (CKO) mice and explored behavioral phenotypes in these mice. We observed that deletion of <i>DCC</i> in cortical layer VI but not layer V led to deficits in fear and spatial memory, as well as defective sensorimotor gating revealed by the prepulse inhibition test (PPI). Critically, the defective sensorimotor gating could be restored by olanzapine, an antipsychotic drug. Furthermore, we found that the levels of p-AKT and p-GSK3α/β were decreased, which was responsible for impaired PPI in the <i>DCC</i>-deficient mice. Finally, the <i>DCC</i>-deficient mice also displayed reduced spine density of pyramidal neurons and disturbed delta-oscillations. Our data, for the first time, identified and explored downstream substrates and signaling pathway of DCC which supports the hypothesis that DCC is a SZ-related risky gene and when defective, may promote SZ-like pathogenesis and behavioral phenotypes in mice.","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"16 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perivascular phosphorylated TDP-43 inclusions are associated with Alzheimer's disease pathology and loss of CD146 and Aquaporin-4","authors":"Jessica Santiago, Dovilė Pocevičiūtė, , Malin Wennström","doi":"10.1111/bpa.13304","DOIUrl":"https://doi.org/10.1111/bpa.13304","url":null,"abstract":"The majority of patients with Alzheimer's disease (AD) exhibit aggregates of Trans-active response DNA binding protein 43 (TDP-43) in their hippocampus, which is associated with a more aggressive disease progression. The TDP-43 inclusions are commonly found in neurons, but also in astrocytes. The impact of the inclusions in astrocytes is less known. In the current study, we investigate the presence of phosphorylated TDP-43 (pTDP-43) inclusions in astrocytic endfeet and their potential association with blood–brain barrier (BBB) damage, glymphatic system dysfunction, and AD pathology. By staining postmortem hippocampal sections from AD patients and non-demented controls against TDP-43 and pTDP-43 together with the astrocytic markers glial fibrillary acidic protein (GFAP), astrocytic endfeet marker Aquaporin-4 (AQP4), and markers for BBB alterations (CD146) and leakiness (Immunoglobulin A), we demonstrate a close association between perivascular pTDP-43 or TDP-43 inclusions and GFAP or AQP4. These perivascular inclusions were more prominent in AD and correlated with the disease severity and loss of CD146 and AQP4. The findings indicate a relationship between pTDP-43 accumulation in astrocytic endfeet and BBB and glymphatic system dysfunction, which may contribute to the downstream pathological events seen in AD patients and the aggressive disease progression.","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"414 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142213664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lack of classical astroblastoma features in pediatric MN1::BEND2-fused brain tumors.","authors":"Nicholas Chapman, Mohammed Iqbal, Adam D Walker, Debra Hawes, Tom Belle Davidson, Nathan Robison, Benita Tamrazi, Jianling Ji, Mark D Krieger, Jennifer A Cotter","doi":"10.1111/bpa.13297","DOIUrl":"https://doi.org/10.1111/bpa.13297","url":null,"abstract":"<p><p>Three distinct MN1::BEND2 fusion-positive tumors in pediatric patients. (A) Clinical course for each patient was variable in part due to differences in initial diagnosis. Each patient responded favorably to gross total resection and is stable at last follow-up. (B) Histologic diversity, lack of prominent classical astroblastoma features, and variable immunoexpression of key markers makes microscopic diagnosis challenging.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13297"},"PeriodicalIF":5.8,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing GBA1-Parkinson's disease and idiopathic Parkinson's disease: α-Synuclein oligomers and synaptic density as biomarkers in the skin biopsy","authors":"Samanta Mazzetti,&nbsp;Elena Contaldi,&nbsp;Milo Jarno Basellini,&nbsp;Claudia Novello,&nbsp;Alessandra Maria Calogero,&nbsp;Letizia Straniero,&nbsp;Federica Garrì,&nbsp;Valentina Ferri,&nbsp;Daniela Calandrella,&nbsp;Francesca Del Sorbo,&nbsp;Rosanna Asselta,&nbsp;Emanuele Cereda,&nbsp;Graziella Cappelletti,&nbsp;Ioannis Ugo Isaias,&nbsp;Gianni Pezzoli","doi":"10.1111/bpa.13284","DOIUrl":"10.1111/bpa.13284","url":null,"abstract":"<p>The main genetic risk factors for Parkinson's disease (PD) are presently represented by variants in <i>GBA1</i> gene encoding for the β-glucocerebrosidase (GCase). Searching for a peripheral biomarker that can be used for selecting and monitoring patients in clinical trials targeting <i>GBA1</i>-associated PD (<i>GBA1</i>-PD) is a current challenge. We previously demonstrated that α-synuclein oligomers expressed as proximity ligation assay (PLA) score in synaptic terminals of skin biopsy are a reliable biomarker for distinguishing idiopathic PD (iPD) from healthy controls (HC). This cross-sectional study investigates an unexplored cohort of <i>GBA1</i>-PD (<i>n</i> = 27) compared to 28 HC, and 36 iPD cases to (i) analyze α-synuclein oligomers and quantify them throughout PLA score, (ii) investigate GCase expression in brain and synaptic terminals targeting the sweat gland, (iii) unravel indicators that could differentiate patients with specific <i>GBA1</i> mutations. PLA score discriminates <i>GBA1</i>-PD from HC with sensitivity = 88.9% (95% CI 70.84–97.65), specificity = 88.5% (95% CI 69.85–97.55), and PPV = 88.9% (95% CI 73.24–95.90), AUC value = 0.927 (95% CI 0.859–0.996). No difference was found between <i>GBA1</i>-PD patients and iPD, suggesting a common pathological pathway based on α-synuclein oligomers. GCase score did not differ in <i>GBA1</i>-PD, iPD, and HC in the synaptic terminals, whereas a positive correlation was found between PLA score and GCase score. Moreover, a significant increase in synaptic density was observed in <i>GBA1</i>-PD compared to iPD and HC (<i>P</i> &lt; 0.0001). Employing ROC curve to discriminate <i>GBA1</i>-PD from iPD, we found an AUC value for synaptic density = 0.855 (95% CI 0.749–0.961) with sensitivity = 85.2% (95% CI 66.27%–95.81%), specificity = 77.1% (95% CI 59.86%–89.58%), and PPV = 74.19% (60.53%–84.35%). The highest synaptic density values were observed in p.N409S patients. This work points out to the value of both PLA score and synaptic density in distinguishing <i>GBA1</i>-PD from iPD and to their potential to stratify and monitor patients in the context of new pathway-specific therapeutic options.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}