Brain Pathology最新文献

{"title":"Spliceosome protein alterations differentiate hubs of the default mode connectome during the progression of Alzheimer's disease","authors":"Sylvia E. Perez,&nbsp;Muhammad Nadeem,&nbsp;Bin He,&nbsp;Jennifer C. Miguel,&nbsp;David G. Moreno,&nbsp;Marta Moreno-Rodriguez,&nbsp;Michael Malek-Ahmadi,&nbsp;Chadwick M. Hales,&nbsp;Elliott J. Mufson","doi":"10.1111/bpa.70004","DOIUrl":"10.1111/bpa.70004","url":null,"abstract":"<p>Default mode network (DMN) is comprised in part of the frontal (FC), precuneus (PreC), and posterior cingulate (PCC) cortex and displays amyloid and tau pathology in Alzheimer's disease (AD). The PreC hub appears the most resilient to AD pathology, suggesting differential vulnerability within the DMN. However, the mechanisms that underlie this differential pathobiology remain obscure. Here, we investigated changes in RNA polymerase II (RNA pol II) and splicing proteins U1-70K, U1A, SRSF2, and hnRNPA2B1, phosphorylated AT8 tau, 3R and 4Rtau isoforms containing neurons and amyloid plaques in layers III and V–VI in FC, PreC, and PCC obtained from individuals with a preclinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI), and mild/moderate mAD. We found a significant increase in pS5-RNA pol II levels in FC NCI, U1-70K in PreC MCI and mAD, and hnRNPA2B1 and SRSF2 levels in PCC mAD. 1N3Rtau levels were significantly increased in FC, decreased in PreC in mAD, and unchanged in PCC, whereas 1N4Rtau increased in mAD across the hubs. SRSF2, U1-70K, U1A, and hnRNPA2B1 nuclear optical density (OD), size, and number were unchanged across groups in FC and PCC, while PreC OD hnRNPA2B1 was significantly greater in mAD. Mislocalized U1A and U1-70K tangle-like structures were found in a few PCC cases and colocalized with AT8-bearing neurofibrillary tangles (NFTs). FC pS5-RNA pol II, PreC U1-70K, Pre pS5,2-RNA pol II, and PCC hnRNPA2B1 and SRSF2 protein levels were associated with cognitive decline but not neuropathology across clinical groups. By contrast, splicing protein nuclear OD measures, size, counts, and mislocalized U1-70K and U1A NFT-like structures were not correlated with NFT or plaque density, cognitive domains, and neuropathological criteria in DMN hubs. Findings suggest that RNA splicing protein alterations and U1 mislocalization contribute differentially to DMN pathogenesis and cognitive deterioration in AD.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 5","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691297","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":"Intraventricular mass in a 52-year-old woman","authors":"Felix Mircea Brehar,&nbsp;Alexandra Mihaela Pătrășcan,&nbsp;Mihaela Andreescu,&nbsp;Laura-Gabriela Țîrlea,&nbsp;Sabina-Loredana-Georgiana Olteanu,&nbsp;Simon Schallenberg,&nbsp;Mihnea P. Dragomir,&nbsp;George E. D. Petrescu","doi":"10.1111/bpa.70003","DOIUrl":"10.1111/bpa.70003","url":null,"abstract":"&lt;p&gt;A 52-year-old woman, without previous medical history, presented to our hospital with acute onset of headache, dizziness, and fatigability. Brain magnetic resonance imaging (MRI) revealed a 17.4 mm × 15.4 mm × 23.5 mm solitary, circumscribed, well-defined enhancing mass, centered on the trigone of the left lateral ventricle. Radiological findings were suggestive of intraventricular meningioma (Figure 1). The patient underwent surgery, and a gross total resection was performed. The intraoperative macroscopic findings were typical for a meningioma—the tumor was overly fibrous, well-defined, firm, encapsulated, and attached to the ventricular walls and choroid plexus.&lt;/p&gt;&lt;p&gt;Histological examination revealed a tumor composed of a mixture of diffuse infiltrates of medium-sized lymphocytes with rounded and angled nuclei and relatively abundant pale cytoplasm, and plasmacytoid cells with paracentric nuclei, wheel-like chromatin, and eosinophilic cytoplasm (Figure 2A, Box 1). A lymphoplasmacytic meningioma was suspected, and immunohistochemistry (IHC) was performed to confirm the diagnosis. The medium-sized lymphocytes mainly expressed CD20 (Figure 2B) and CD79a and were negative for CD5 (Figure 2C) and CD3; therefore, they could be assigned to the B-cell lineage, suggesting B-cell non-Hodgkin-lymphoma (B-NHL) accompanied by a physiological CD3, CD5 T-cell infiltrate. The B-lymphocytes and plasma cells also showed a monotypic expression of the immunoglobulin light chain kappa (kappa/lambda ratio: &gt;10/1, Figure 2D,E). Immunohistochemically, there was no evidence of aberrant expression of CD10, BCL6, CD23, CyclinD1, MUM1, EMA, or progesterone receptor and therefore, there was no evidence of B-CLL, mantle cell lymphoma, follicular lymphoma, or meningioma. The proliferation index (Ki-67) was low (~15%, Figure 2F), consistent with the diagnosis of indolent B-NHL.&lt;/p&gt;&lt;p&gt;Serum protein electrophoresis and immunofixation showed no serum immunoglobulin abnormalities. A sternal bone marrow biopsy was performed, with normal findings.&lt;/p&gt;&lt;p&gt;Primary intraventricular marginal zone B-cell lymphoma was diagnosed.&lt;/p&gt;&lt;p&gt;Extranodal marginal zone lymphoma (EMZL) is an indolent, small B-cell neoplasm that can be found in any extranodal location, but most frequently in the gastrointestinal tract (MALT lymphoma). [&lt;span&gt;1&lt;/span&gt;] In rare cases, MALT lymphomas may develop in tissues without mucosa, including the central nervous system. Ventricular invasion of a parenchymal primary CNS lymphoma occurs in up to 10.6% of cases, but an exclusively intraventricular form is very rare. [&lt;span&gt;1-3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;MALT lymphomas have the ability to mimic meningiomas on imaging, dural-based masses being the most common appearance. [&lt;span&gt;2&lt;/span&gt;] Despite the lack of mucosa in the brain tissue, it is suggested that intraventricular MALT lymphomas may be mistaken for meningiomas because arachnoid cap cells (contained within the choroid plexus) serve as a surrogate for mucosal epithel","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 3","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596259","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":"Sterol imbalances and cholesterol-24-hydroxylase dysregulation is linked to the underlying progression of multiple sclerosis","authors":"Lauren Griffiths,&nbsp;Kristen Hawkins,&nbsp;Eylan Yutuc,&nbsp;Roberto Angelini,&nbsp;Racheal Fosuah,&nbsp;Manuela Pacciarini,&nbsp;Alison Dickson,&nbsp;Neil Robertson,&nbsp;Laura Childs,&nbsp;Samantha Loveless,&nbsp;Emma Tallantyre,&nbsp;William J. Griffiths,&nbsp;Yuqin Wang,&nbsp;Owain W. Howell","doi":"10.1111/bpa.70001","DOIUrl":"10.1111/bpa.70001","url":null,"abstract":"<p>Disability worsening in multiple sclerosis (MS) is linked to neurodegeneration. Cholesterol homeostasis is essential for normal brain function. CYP46A1, crucial for brain cholesterol turnover and reduced in some neurodegenerative diseases, is a potential neuroprotective target. We hypothesized that CYP46A1 is downregulated in MS brains and linked to cholesterol dysbalance. Mass spectrometric analysis of sterols was performed from matched plasma and cerebrospinal fluid (CSF) in an all-female MS cohort (<i>n</i> = 32, mean age = 33). Disability status was recorded at baseline and follow-up. MS brain tissue samples (<i>n</i> = 11; 7 females; ages 38–67; 10 Secondary Progressive MS, 1 Primary Progressive MS; Disease Duration: 13–49 years) and control samples (<i>n</i> = 8; 3 females; ages 41–68) analysed for pathological regions using mass spectrometry and RNA expression using in-situ hybridization. Significant dysregulation in 25-hydroxycholesterol, 27-hydroxycholesterol and 3β-hydroxycholestenoic acid in CSF correlated with disability at baseline and follow-up in the patient population. In brain tissue, reduced cholesterol, 24S-hydroxycholesterol and 24S,25-epoxycholesterol were observed in white matter lesions (<i>p</i> &lt; 0.05), linked to CYP46A1 activity. CYP46A1 expression was enriched in neurons, with reductions in MS grey matter lesions and non-lesions compared to controls (<i>p</i> &lt; 0.01). Cholesterol metabolism is dysregulated in MS and is associated with reduced neuron-specific CYP46A1 expression. Modulating CYP46A1, a druggable target, may benefit progressive MS.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 5","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566189","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 6-year-old female with synchronous cerebellar and thalamic masses","authors":"Wenjun Luo,&nbsp;Cuiyun Sun,&nbsp;Zhendong Jiang,&nbsp;Rongju Zhang,&nbsp;Wengao Zhang,&nbsp;Shizhu Yu","doi":"10.1111/bpa.70005","DOIUrl":"10.1111/bpa.70005","url":null,"abstract":"&lt;p&gt;A 6-year-old girl was admitted to our hospital for sudden-onset headache with vomiting. Ataxia was observed via physical examination, and two well-defined lesions were identified via MRI, one in the left cerebellum, measuring approximately 42 mm× 37 mm in size, which was mainly T1-hyperintense, T2-hypointense (Figure 1), with T1-hypointense and T2-hyperintense in its inner and edge parts, and without enhancement in the center of T1-weighted postcontrast, and the other in the right thalamus, which was cystic, measuring 15 mm× 15 mm, with T2-hyperintense (Figure 1, inset) and T1-hypointense, both of which provided the first impressions of hemorrhagic lesions. The cerebellar lesion was excised for definitive diagnosis and symptom relief, whereas the thalamic lesion was left under close monitoring and eventually removed 5 months later after another episode of headache due to a volume increase confirmed by MRI in the patient's local hospital (Box 1).&lt;/p&gt;&lt;p&gt;Haematoxylin and eosin (H&amp;E) staining revealed that the cerebellar tumour was predominantly solid with medium cell density. The tumour cells were uniform, mainly with clear vacuolated cytoplasm and elongated processes. Oligodendroglial-like cells were observed in some areas (Figure 2A), and branching capillaries were scattered in the stroma, along with intratumoural hemorrhage and cystic alterations (Box 1). Mitoses were easily observed (5 mitoses per 10 HPF), but microvascular proliferation and palisading necrosis were absent. Immunohistochemical staining revealed that GFAP (Figure 2B), CD56 and H3K27me3 were diffusely positive; S-100 and p53 were mostly positive; and nearly half of the tumour cells were NeuN positive (Figure 2C), whereas OLIG2 was negative (Figure 2B, inset). Synaptophysin (SYN) and EMA immunoreactivities were notably present in a significant portion of the tumour cells in a paranuclear dot-like pattern (Figure 2D,E, inset). The Ki-67 labelling index was 15%.&lt;/p&gt;&lt;p&gt;During whole-exome high-throughput sequencing, two clinically relevant alterations, &lt;i&gt;EGFR&lt;/i&gt; amplification and &lt;i&gt;TP53&lt;/i&gt; mutation, were found. The paraffin-embedded tumour tissue was then subjected to a genome-wide DNA methylation assay via the Human Methylation 850K array platform. The methylation profile in version 12.8 of the publicly accessible Heidelberg classifier matched the methylation class ‘diffuse paediatric-type high-grade glioma (pHGG), H3-wild type and IDH-wild type’ RTK2 (pHGG RTK2), with a score &gt;0.9. MGMT promoter methylation was present. The copy number profile derived from the methylation array revealed changes consistent with EGFR amplification and gains of chromosomes 7, 8, 16, 14q and 17 p.&lt;/p&gt;&lt;p&gt;The thalamic lesion operation was performed at the patient's local hospital. The histopathological and immunohistochemical features of the thalamic lesion were consistent with the cerebellar lesion after careful comparison by two independent pathologists. Unfortunately, extensive bleeding ma","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555895","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 16-year-old female with an intrasellar mass","authors":"Yinbo Xiao,&nbsp;Can Yin,&nbsp;Junliang Lu,&nbsp;Shuangni Yu,&nbsp;Zhen Huo,&nbsp;Zhiyong Liang","doi":"10.1111/bpa.70002","DOIUrl":"10.1111/bpa.70002","url":null,"abstract":"&lt;p&gt;A 16-year-old girl presented to the clinic with a 2-year history of weight gain. In the last week, she had developed blepharoptosis and blurred vision, with headache and vomiting. She did not have a prior history of tumors. Physical examination showed a moon face, buffalo hump, and purpura. Laboratory findings showed elevated 24-hour urinary free cortisol (UFC) and plasma adrenocorticotropic hormone (ACTH). The low-dose dexamethasone suppression test failed to suppress cortisol production, but the high-dose test did. Magnetic resonance imaging (MRI) revealed a 15.9 × 10.1 × 12.8 mm&lt;sup&gt;3&lt;/sup&gt; sellar mass with heterogeneous T1 signal enhancement (Figure 1). It extended into the bilateral cavernous sinuses and the suprasellar cistern, impacting the optic chiasm. Surgery was pursued for a definitive diagnosis and tumor debulking (Box 1).&lt;/p&gt;&lt;p&gt;Histopathological examination revealed a biphasic tumor with a neuroendocrine and a mesenchymal component. The neuroendocrine component, with well-differentiated solid or glandular structures, showed positive staining for Synaptophysin (Syn), ACTH, and transcription factors T-PIT and INSM-1 but negative for PIT-1 and SF-1 (Figure 2). The mesenchymal component in the stromal background was composed of spindle or irregular cells with large nuclei and abundant eosinophilic cytoplasm. These tumor cells were positive for Desmin, MyoD1, and Myogenin (Figure 2). Unlike the neuroendocrine component, the mesenchymal component exhibited strong nuclear p53 positivity and loss of ATRX expression. Mitoses were frequent in the mesenchymal component (up to 8 per 10 HPF). The mitotic count was in keeping with the Ki67 labeling (the Ki67 index was significantly higher in the mesenchymal components [50%] compared with the epithelial cells [3%]). NGS testing identified several pathological mutations as follows: &lt;i&gt;DICER1&lt;/i&gt; (c.4860dup, p.Cys1621Leufs*31), &lt;i&gt;DICER1&lt;/i&gt; (c.5428G&gt;T, p.Asp1810Tyr), &lt;i&gt;TP53&lt;/i&gt; (c.740A&gt;T, p.N247I), &lt;i&gt;ATRX&lt;/i&gt; (c.594+1G&gt;T), and &lt;i&gt;PIK3CA&lt;/i&gt; copy-number gain.&lt;/p&gt;&lt;p&gt;Corticotrophin tumor/adenoma in association with primary intracranial sarcoma, DICER1-mutant.&lt;/p&gt;&lt;p&gt;This is a unique case of a young patient who presented with signs and symptoms of Cushing's disease and was diagnosed post-surgery as “corticotrophin tumor/adenoma associated with primary intracranial sarcoma, DICER1-mutant.” Primary intracranial sarcoma, DICER1-mutant (PIS-DICER1) is a rare molecularly defined entity. According to the 2021 World Health Organization (WHO) CNS tumor classification, it is defined as a primary intracranial sarcoma with distinctive morphology, typically showing immunophenotypic myogenic differentiation [&lt;span&gt;1&lt;/span&gt;]. DICER1 mutations are definite features, commonly along with TP53 mutations and ATRX inactivation. These tumors usually occur in young patients (median age at diagnosis as 6 years) and appear to be aggressive, notably at risk for DICER1 syndrome. Without appropriate genetic testing,","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 3","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555885","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":"Validation of target-enriched enzymatic methylation sequencing for brain tumor classification from formalin-fixed paraffin embedded-derived DNA","authors":"Quynh T. Tran,&nbsp;Sujuan Jia,&nbsp;Md. Zahangir Alom,&nbsp;Lu Wang,&nbsp;Charles G. Mullighan,&nbsp;Ruth G. Tatevossian,&nbsp;Brent A. Orr","doi":"10.1111/bpa.70000","DOIUrl":"10.1111/bpa.70000","url":null,"abstract":"<p>DNA methylation profiling by Illumina methylation array-based methods has revolutionized the molecular classification and diagnosis of brain tumors. A significant barrier to adopting these methods in a clinical environment is the requirement for specialized scanners, which results in high additional costs and a larger laboratory footprint. DNA sequencing-based alternatives are attractive because most clinical molecular pathology laboratories already use sequencers for other molecular assays. This study aimed to compare the utility of the newly developed sequencing-based enzymatic methyl sequencing (EM-seq) method paired with the Twist Human Methylome panel for brain tumor classification with standard Infinium Methylation BeadChip-based methods. We used DNA from fresh-frozen or formalin-fixed, paraffin-embedded (FFPE) brain cancer samples from 19 patients and 1 control sample to construct DNA libraries covering 3.98 million CpG sites. We developed and validated a bioinformatics pipeline to analyze target-enriched EM-seq (TEEM-seq) data in comparison with standard array-based methods for tumor classification and copy number profiling. We found high concordance between TEEM-seq and traditional methods, with high correlation coefficients (&gt;0.98) between FFPE replicates. We successfully classified tumor samples into the expected molecular classes with robust prediction scores (&gt;0.82). We observed that FFPE samples required a sequencing depth of at least 35x to achieve consistently high and reliable prediction scores. The TEEM-seq method has the potential to complement existing tumor classification methods and lower the barriers for the adoption of methylation profiling in routine clinical use.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 5","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522628","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":"Society News","authors":"Audrey Rousseau","doi":"10.1111/bpa.13333","DOIUrl":"https://doi.org/10.1111/bpa.13333","url":null,"abstract":"&lt;p&gt;&lt;b&gt;The ISN is looking for a group of young motivated neuropathologists&lt;/b&gt; to promote the specialty via the ISN website. If you are interested in participating, please contact Audrey Rousseau (&lt;span&gt;[email protected]&lt;/span&gt;) or Monika Hofer (&lt;span&gt;[email protected]&lt;/span&gt;).&lt;/p&gt;&lt;p&gt;&lt;b&gt;The International Congress of Neuropathology (ICN)&lt;/b&gt; will be held in Edinburgh, Scotland, in 2027 (ICN27). The Congress President will be Prof Colin Smith, and the ICN27 will be hosted by the British Neuropathological Society (BNS).&lt;/p&gt;&lt;p&gt;“On behalf of the British Neuropathological Society, I am delighted to extend a warm invitation to all our colleagues across the world to join us in Edinburgh for the International Congress of Neuropathology 2027. Edinburgh is an easily accessible center, surrounded by 1000 years of living history. We will develop a strong academic programme covering all aspects of neuropathology with world leading plenary speakers, supported by a social programme highlighting some of Edinburgh's historic charms. For those wishing to explore further, Edinburgh offers access to many of Scotland's highlights, be it touring the Highlands, sampling our famous whisky, or golfing on some of our picturesque courses. I do hope you will be able to join us for what I am sure will be a memorable meeting showcasing the best in international neuropathology.&lt;/p&gt;&lt;p&gt;Colin Smith.&lt;/p&gt;&lt;p&gt;Congress President ISN 2027”&lt;/p&gt;&lt;p&gt;Summary report for ICN23 Berlin (our most recent International Congress of Neuropathology, September 2023) now available in the Society's journal &lt;i&gt;Brain Pathology&lt;/i&gt; (see link: https://doi.org/10.1111/bpa.13249).&lt;/p&gt;&lt;p&gt;We are delighted to start the bidding process for holding the &lt;b&gt;2031 XXII International Congress of Neuropathology (ICN)&lt;/b&gt;. As you know, the 2027 XXI ICN Congress will be in Edinburgh and we now need to think ahead to 2031 and find a new home for our much-loved congress.&lt;/p&gt;&lt;p&gt;The Invitation Letter calling for bids and outlining the process can be found on the ISN website (www.intsocneuropathol.com). Please note that the deadline is the &lt;b&gt;March 1, 2025&lt;/b&gt;.&lt;/p&gt;&lt;p&gt;&lt;b&gt;&lt;i&gt;Brain Pathology has joined Wiley's Open Access&lt;/i&gt;&lt;/b&gt; portfolio as of January 2021. As a result, all submissions are subject to an Article Publication Charge (APC) if accepted and published in the journal. ISN members are eligible for a 10% discount of the Open Access APC. For more information on the fees, please click https://onlinelibrary.wiley.com/page/journal/17503639/article_publication_charges#:~:text=Brain%20Pathology%20is%20an%20Open,of%20CC%20license%20be%20used.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Free resource: digital microscopy platform for neurodegenerative diseases curated in Munich&lt;/b&gt;. Prof Jochen Herms and his team have been setting up a digital microscopy platform for neurodegenerative diseases in their department in Munich. Registration is free. ISN members and interested colleagues are invited to use this resource, which will be particularly useful for teaching and","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 2","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13333","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143438732","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":"An 11-year-old boy with a posterior fossa tumor","authors":"Gina Del Vecchio,&nbsp;Sabina Barresi,&nbsp;Sara Patrizi,&nbsp;Claudia D'Orazio,&nbsp;Silvia Genovese,&nbsp;Isabella Giovannoni,&nbsp;Chantal Tancredi,&nbsp;Anne Falcou,&nbsp;Angela Mastronuzzi,&nbsp;Giovanna Stefania Colafati,&nbsp;Andrea Carai,&nbsp;Viola Alesi,&nbsp;Evelina Miele,&nbsp;Rita Alaggio,&nbsp;Sabrina Rossi","doi":"10.1111/bpa.13332","DOIUrl":"https://doi.org/10.1111/bpa.13332","url":null,"abstract":"<p>An 11-year-old boy was referred to our institution from a resource-limited country with a history of hydrocephalus secondary to a posterior fossa tumor. Magnetic resonance imaging (MRI) revealed a large extra-axial neoplasm located at the tentorium, measuring 5.1 × 4.2 × 4.0 cm (Figure 1), causing marked distortion of the adjacent structures and transtentorial herniation. The lesion was strongly enhancing, associated with massive vasogenic edema. Microsurgical excision of the lesion was performed by a supracerebellar infratentorial approach, obtaining a gross total resection. After recovery, the boy returned to his country, where he has been followed with periodical computed tomography scans. He remains free of disease 58 months from surgery (Box 1).</p><p>The lesion consisted of epithelioid and rhabdoid cells arranged in a chordoid pattern within a myxoid stroma (Figure 2A) with foci of collagen deposition sometimes featuring amianthoid fibers (Figure 2B). Solid sheets of rhabdoid and epithelioid cells with focal clear cell changes were also present. Mitotic figures were infrequent (1/1.96 mm²). There was a sparse lymphoplasmocytic inflammatory infiltrate at the periphery. The possibility of a chordoid meningioma was first considered, and the expression of epithelial membrane antigen (EMA) seemed to support this hypothesis. However, given the rarity of this meningioma subtype and the lack of a specific marker, an extensive immunohistochemical panel was performed: the diffuse desmin expression, combined with focal CD99 and D2-40, prompted us to consider an intracranial mesenchymal tumor (IMT) with FET::CREB fusion (Figure 2C–E). RNA sequencing (Agilent) demonstrated the presence of a <i>SMARCA2::CREM</i> transcript (Figure 2F). No pathogenic/likely pathogenic variants were identified (TSO500). CGH/SNP array revealed only a mosaic 12p trisomy. Genome-wide DNA methylation profiling classified the lesion as meningioma (score 0.98), subclass 3 (score 0.93) according to the Heidelberg Brain Tumor Classifier v12.5. t-distributed stochastic neighbor embedding (t-SNE) analysis was performed using selected Deutsches Krebsforschungszentrum (German Cancer Research Center) (DFKZ) reference classes and two previously characterized IMT cases, both harboring an <i>EWSR1::CREM</i> fusion. The current case clustered with one of the IMT and was close to meningiomas, whereas the other IMT was near angiomatoid fibrous histiocytomas (Figure 2G).</p><p>IMT harboring a <i>SMARCA2::CREM</i> fusion.</p><p>We describe a rare example of a pediatric posterior fossa IMT with a <i>SMARCA2::CREM</i> fusion. A case with an identical fusion transcript has been reported in the parietal lobe of a 40-year-old man with a 15-year history of multiple recurrences of a “chordoid meningioma” [<span>1</span>]. These cases share a striking chordoid morphology. IMT generally shows two main patterns: (i) stellate/spindle cells and abundant myxoid stroma preferentially character","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 2","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13332","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143438731","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":"Peripheral blood-derived immune cell counts as prognostic indicators and their relationship with DNA methylation subclasses in glioblastoma patients","authors":"Benedikt Asey,&nbsp;Tobias F. Pantel,&nbsp;Malte Mohme,&nbsp;Yahya Zghaibeh,&nbsp;Lasse Dührsen,&nbsp;Dana Silverbush,&nbsp;Ulrich Schüller,&nbsp;Richard Drexler,&nbsp;Franz L. Ricklefs","doi":"10.1111/bpa.13334","DOIUrl":"10.1111/bpa.13334","url":null,"abstract":"<p>Glioblastomas are known for their immunosuppressive tumor microenvironment, which may explain the failure of most clinical trials in the past decade. Recent studies have emphasized the significance of stratifying glioblastoma patients to predict better therapeutic responses and survival outcomes. This study aims to investigate the prognostic relevance of peripheral immune cell counts sampled prior to surgery, with a special focus on methylation-based subclassification. Peripheral blood was sampled in patients with newly diagnosed (<i>n</i> = 176) and recurrent (<i>n</i> = 41) glioblastoma at the time of surgery and analyzed for neutrophils, monocytes, leukocytes, platelets, neutrophil–lymphocyte ratio, lymphocyte–monocyte ratio, and platelet–lymphocyte ratio. Peripheral immune cell counts were correlated with patients' survival after combined radiochemotherapy. In addition, 850 k genome-wide DNA methylation was assessed on tissue for defining tumor subclasses and performing cell-type deconvolution. In newly diagnosed glioblastoma, patients with higher peripheral neutrophil counts had an unfavorable overall survival (OS) (<i>p</i> = 0.01, median overall-survival (mOS) 17.0 vs. 10.0 months). At the time of first recurrence, a significant decrease of peripheral immune cell counts was observed, and elevated monocyte (<i>p</i> = 0.03), neutrophil (<i>p</i> = 0.04), and platelet (<i>p</i> = 0.01) counts were associated with poorer survival outcomes. DNA methylation subclass-stratified analysis revealed a significant survival influence of neutrophils (<i>p</i> = 0.007) and lymphocytes (<i>p</i> = 0.04) in the mesenchymal (MES) subclass. Integrating deconvolution of matched tumor tissue showed that platelets and monocytes were correlated with a more differentiated, tumor-progressive cell state, and peripheral immune cell counts were most accurately reflected in tissue of the MES subclass. This study illustrates a restricted prognostic significance of peripheral immune cell counts in newly diagnosed glioblastoma and a constrained representation in matched tumor tissue, but it demonstrates a more pertinent situation at the time of recurrence and after DNA methylation-based stratification.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13334","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122191","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":"Brain-derived textiloma post glioblastoma resection and application of oxidized regenerated cellulose: A pilot, bedside-to-bench, translational study","authors":"Joshua A. Kra,&nbsp;Christopher Markosian,&nbsp;Fenny H. F. Tang,&nbsp;Ada Baisre de León,&nbsp;Anupama Chundury,&nbsp;Pankaj K. Agarwalla,&nbsp;Daniela I. Staquicini,&nbsp;Renata Pasqualini,&nbsp;Wadih Arap","doi":"10.1111/bpa.13331","DOIUrl":"10.1111/bpa.13331","url":null,"abstract":"<p>Oxidized regenerated cellulose (ORC; marketed as Surgicel® and Tabotamp®) is routinely used as an intraoperative hemostatic agent. Rarely, residual ORC has been associated with a foreign body reaction generating cystic or granulomatous lesions (i.e., textilomas) at the surgical site. Here, we report a bedside-to-bench, translational report of an intracranial mass after neurosurgical resection of glioblastoma with ORC application. As part of patient care, we performed magnetic resonance imaging and histopathological analysis of the mass. We then performed in vitro studies to evaluate the effect of ORC on cytokine production and viability of BV-2 murine microglial cells by using quantitative PCR along with live cell microscopy and crystal violet staining, respectively. Magnetic resonance imaging demonstrated a recurrent mass pressing on the adjacent right ventricle, which was removed in a second surgery for diagnostic and therapeutic purposes. Unexpectedly, histopathological examination of the resected mass revealed abundant ORC arising from the site with inflammation, microglial activation, and collagenization. Mechanistically, we show an ORC-induced modest increase in inflammatory cytokines with a subsequent decrease in microglial cell viability. These findings suggest that ORC may mediate microglial immune response and viability, and serve to raise awareness and guide interpretation of post-treatment surveillance imaging findings in the instance of foreign body reaction.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13331","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000542","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}