Brain Pathology最新文献

{"title":"Comparison of automated and manual approaches for microglial quantification and classification: A focus on the HALO digital pathology platform.","authors":"Laura M Carr, Bianca Guglietti, Ing Chee Wee, Ian F Musgrave, Sanam Mustafa, Frances Corrigan, Lyndsey E Collins-Praino","doi":"10.1111/bpa.70036","DOIUrl":"10.1111/bpa.70036","url":null,"abstract":"<p><p>Phenotypic changes in microglia have been linked to multiple neurological conditions, such as dementia, Parkinson's disease, stroke and traumatic brain injury. Consistent identification and classification of microglia is essential in understanding potential links with neurological diseases. Currently, there are several ways by which the microglial population and morphology are assessed, including manually or using open-source image analysis platforms, such as ImageJ. A microglial classification module for the HALO digital pathology platform has been developed for this purpose but has not yet been validated within the literature. The current study therefore conducted a comparison of the performance of this HALO module to manual microglial analysis and to automated analysis via ImageJ using both human and rat brain tissue. In 5 μm thick human tissue, total and activated microglia/mm² counted by HALO showed strong positive correlations with both manual and ImageJ counts. HALO did not differ from the other methods for total microglia counts; however, Halo did differ from both manual and ImageJ methods in the number of activated microglia detected within the substantia nigra. In 20 μm rat tissue, total counts derived from HALO showed moderate positive correlations with both manual and ImageJ counting; however, activated counts on Halo were not positively correlated with any method. To our knowledge, this is the first study to systematically compare the Halo module to other common methods of microglia analysis. When applied to 5 μm tissue, the Halo module is comparable to manual counting and to automated analysis on ImageJ. However, when analyzing thicker tissue, Halo struggles to perform in line with these other methods, particularly for counts of activated microglia, likely due to increased cell density and the morphological complexity of microglia. These results highlight the importance of carefully tailoring image analysis parameters on automated counting methods to suit the needs of the tissue.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70036"},"PeriodicalIF":6.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871570","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":"SOCIETY NEWS","authors":"Audrey Rousseau","doi":"10.1111/bpa.70031","DOIUrl":"10.1111/bpa.70031","url":null,"abstract":"<p><b>The ISN is looking for a group of young motivated neuropathologists</b> to promote the specialty via the ISN website. If you are interested in participating, please contact Audrey Rousseau (<span>[email protected]</span>) or Monika Hofer (<span>[email protected]</span>).</p><p><b>The International Congress of Neuropathology (ICN)</b> 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).</p><p>“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 centre, 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.</p><p>Colin Smith</p><p>Congress President ISN 2027”</p><p>Summary report for ICN23 Berlin (our most recent International Congress of Neuropathology, September 2023) now available in the Society's journal Brain Pathology (see link: https://doi.org/10.1111/bpa.13249).</p><p>We are delighted to start the bidding process for holding the <b>2031 XXII International Congress of Neuropathology (ICN)</b>. 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.</p><p>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 <b>31st August 2025</b>.</p><p>The <b>7th Quadrennial Meeting of the World Federation of Neuro-Oncology Societies</b> will be held in conjunction with the 30th Annual Meeting &amp; Education Day of the Society for Neuro-Oncology <b>November 19-23, 2025</b> in Honolulu, Hawaii.</p><p><b><i>Brain Pathology has joined Wiley's Open Access</i></b> 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 off the Open Access APC. For more information on the fees, please click here.</p><p><b><i>Free resource: digital microscopy platform for neurodegenerative diseases curated in Munich</i></b>. 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 int","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 5","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783530","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":"The physiological and pathological effects of sphingolipid metabolism and signaling in the central nervous system.","authors":"Tian Li, Haoying He, Ejuan Zhang, Fengjiao Hu, Zhuo Wang, Jian Xu, Mengliu Zeng, Biwen Peng","doi":"10.1111/bpa.70033","DOIUrl":"https://doi.org/10.1111/bpa.70033","url":null,"abstract":"<p><p>Sphingolipids are essential, complex lipids that are abundant in the cell membranes of eukaryotic cells, particularly concentrated in the myelin and neuronal membranes of the central nervous system (CNS). These lipids are crucial components of the cell membrane, affecting their structure and fluidity, and thus regulating various biological processes, including signal transduction, cell differentiation, apoptosis, and autophagy. The metabolic pathways of sphingolipids are highly complex and conserved, and this metabolic process can produce multiple metabolites. Metabolites such as ceramide (Cer) and sphingosine-1-phosphate (S1P) are vital in CNS signaling, affecting neurodevelopment, myelination, and synaptic plasticity. Thus, disruption of sphingolipid metabolism is closely related to neurological disorders. This article provides the latest studies concerning the known features of sphingolipid and sphingolipid metabolism, highlighting its physiological and pathological roles in the CNS.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70033"},"PeriodicalIF":6.2,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759241","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":"Dysregulation of the endosomal sorting complex III is linked to neurodegeneration in progressive multiple sclerosis.","authors":"Carmen Picon, Robertas Aleksynas, Marcelina Wojewska, Francesco de Virgiliis, Doron Merkler, Richard Reynolds","doi":"10.1111/bpa.70034","DOIUrl":"https://doi.org/10.1111/bpa.70034","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic neuroinflammatory disease that progresses to a stage marked by irreversible neurological decline and widespread neurodegeneration. Necroptosis, a regulated form of cell death primarily triggered by tumor necrosis factor (TNF), has been implicated in neuronal loss in progressive MS. The Endosomal Sorting Complex Required for Transport (ESCRT) machinery, essential for plasma membrane repair and vesicle trafficking, is known to counteract necroptosis in non-neural cells. In this study, we investigated whether ESCRT dysfunction contributes to neurodegeneration in the MS cortex. We identified a significant dysregulation of ESCRT-III complex components, particularly VPS4B and CHMP2A, in neurons of MS cortical grey matter. This dysregulation correlated with reduced neuronal density and increased meningeal inflammation. Notably, both demyelinated and normal-appearing grey matter showed decreased VPS4B, while CHMP2A loss was more restricted to areas of demyelination. These findings suggest that impaired ESCRT-III function may increase neuronal vulnerability to necroptosis and contribute to disease progression in MS. Our results highlight a novel pathway linking neuroinflammation, ESCRT dysfunction, and neuronal death, with potential therapeutic implications for neuroprotection in progressive MS.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70034"},"PeriodicalIF":5.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706408","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":"Dendritic location of dystrophic neurites in FTLD-TDP type C with annexinopathy.","authors":"Allegra Kawles, Antonia Zouridakis, Caroline Nelson, Rachel Keszycki, Grace Minogue, Alyssa Macomber, Pouya Jamshidi, Rudolph J Castellani, Changiz Geula, Tamar Gefen, M-Marsel Mesulam","doi":"10.1111/bpa.70032","DOIUrl":"10.1111/bpa.70032","url":null,"abstract":"<p><p>The type C variant (TDP-C) of FTLD-TDP exhibits unique features, not shared by types A and B, namely the invariable and frequently asymmetric predilection for the anterior temporal lobes (ATL). Depending on the direction of hemispheric asymmetry, the associated clinical features include word comprehension impairment, associative agnosia, and behavioral abnormalities. Current research on TDP-C aims to explore the factors that underlie the selective targeting of the ATL and, more specifically, the cellular details that undermine the behavioral and cognitive functions of this region. Abnormal TDP-C neurites have recently been shown to represent heterodimers with annexin A11 (ANXA11). This feature, not shared by TDP-A or -B, may explain the unique predilection of TDP-C for the ATL. To further explore the subcellular distribution of the pathology, paraffin-embedded sections were stained using fluorescent antibodies for the dendritic marker MAP2 and phosphorylated TDP-43 (pTDP) or ANXA11. Results indicated that approximately half of pTDP/ANXA11 neurites co-localized with MAP2. The actual overlap during life may be much higher but decreased at autopsy through dendritic loss due to prolonged neurodegeneration. The potentially selective and progressive dendritic pathology of TDP-C, quite unique among neurodegenerative entities, may underlie the distinctive perturbation of cortical integrative computations.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70032"},"PeriodicalIF":6.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697701","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":"Intraventricular mass in a 49-year-old male.","authors":"Connor R Zuraski, Donald P Pizzo, Jessica D Schulte, Vanessa S Goodwill","doi":"10.1111/bpa.70030","DOIUrl":"https://doi.org/10.1111/bpa.70030","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70030"},"PeriodicalIF":5.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559269","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":"Pediatric brain tumor classification using digital pathology and deep learning: Evaluation of SOTA methods on a multi-center Swedish cohort.","authors":"Iulian Emil Tampu, Per Nyman, Christoforos Spyretos, Ida Blystad, Alia Shamikh, Gabriela Prochazka, Teresita Díaz de Ståhl, Johanna Sandgren, Peter Lundberg, Neda Haj-Hosseini","doi":"10.1111/bpa.70029","DOIUrl":"https://doi.org/10.1111/bpa.70029","url":null,"abstract":"<p><p>Brain tumors are the most common solid tumors in children and young adults, but the scarcity of large histopathology datasets has limited the application of computational pathology in this group. This study implements two weakly supervised multiple-instance learning (MIL) approaches on patch features obtained from state-of-the-art histology-specific foundation models to classify pediatric brain tumors in hematoxylin and eosin whole slide images (WSIs) from a multi-center Swedish cohort. WSIs from 540 subjects (age 8.5 ± 4.9 years) diagnosed with brain tumors were gathered from the six Swedish university hospitals. Instance (patch)-level features were obtained from WSIs using three pre-trained feature extractors: ResNet50, UNI, and CONCH. Instances were aggregated using attention-based MIL (ABMIL) or clustering-constrained attention MIL (CLAM) for patient-level classification. Models were evaluated on three classification tasks based on the hierarchical classification of pediatric brain tumors: tumor category, family, and type. Model generalization was assessed by training on data from two of the centers and testing on data from four other centers. Model interpretability was evaluated through attention mapping. The highest classification performance was achieved using UNI features and ABMIL aggregation, with Matthew's correlation coefficient of 0.76 ± 0.04, 0.63 ± 0.04, and 0.60 ± 0.05 for tumor category, family, and type classification, respectively. When evaluating generalization, models utilizing UNI and CONCH features outperformed those using ResNet50. However, the drop in performance from the in-site to out-of-site testing was similar across feature extractors. These results show the potential of state-of-the-art computational pathology methods in diagnosing pediatric brain tumors at different hierarchical levels with fair generalizability on a multi-center national dataset.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70029"},"PeriodicalIF":5.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526500","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":"Multi-pronged analysis of pediatric low-grade glioma and ganglioglioma reveals a unique tumor microenvironment associated with BRAF alterations","authors":"Shadi Zahedi,&nbsp;Kent Riemondy,&nbsp;Tian Liu,&nbsp;Andrea M. Griesinger,&nbsp;Andrew M. Donson,&nbsp;April A. Apfelbaum,&nbsp;Rui Fu,&nbsp;Julian Grandvallet Contreras,&nbsp;Michele Crespo,&nbsp;John DeSisto,&nbsp;Madeline M. Groat,&nbsp;Emil Bratbak,&nbsp;Adam Green,&nbsp;Todd C. Hankinson,&nbsp;Michael Handler,&nbsp;Rajeev Vibhakar,&nbsp;Nicholas Willard,&nbsp;Nicholas K. Foreman,&nbsp;Tzu Phang,&nbsp;Jean Mulcahy Levy","doi":"10.1111/bpa.70023","DOIUrl":"10.1111/bpa.70023","url":null,"abstract":"<p>Pediatric low-grade gliomas (pLGG) comprise 35% of all brain tumors. Despite favorable survival, patients experience significant morbidity from disease and treatments. A deeper understanding of pLGG biology is essential to identify novel, more effective, and less toxic therapies. We utilized single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and cytokine analyses to characterize and understand tumor and immune cell heterogeneity of pilocytic astrocytoma (PA) and ganglioglioma (GG). scRNA-seq revealed tumor and immune cells within the tumor microenvironment (TME). Tumor cell subsets include both progenitor and mature cell populations. Immune cells included myeloid and lymphocytic cells. There was a significant difference between the prevalence of two major myeloid subclusters between PA and GG. Bulk and single-cell cytokine analyses evaluated the immune cell signaling cascade with distinct immune phenotypes among tumor samples. <i>KIAA1549-BRAF</i> tumors appeared more immunogenic, secreting higher levels of immune cell activators and chemokines, compared to <i>BRAF V600E</i> tumors. Spatial transcriptomics revealed the differential gene expression of these chemokines and their location within the TME. A multi-pronged analysis demonstrated the complexity of the PA and GG TME and differences between genetic drivers that may influence their response to immunotherapy. Further investigation of immune cell infiltration and tumor-immune interactions is warranted.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526499","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 posterior fossa mass in a 4-year-old female","authors":"Vy Huynh,&nbsp;M. Adelita Vizcaino,&nbsp;Jonathan D. Schwartz,&nbsp;J. Zachary Wilson,&nbsp;David J. Daniels,&nbsp;Julie B. Guerin,&nbsp;Benjamin R. Kipp,&nbsp;Brent A. Orr,&nbsp;Kenneth Aldape,&nbsp;Yi Zhu","doi":"10.1111/bpa.70028","DOIUrl":"10.1111/bpa.70028","url":null,"abstract":"&lt;p&gt;A 4-year-old female presented to the emergency department with persistent headaches, vomiting, and balance difficulties for 1 month. Neurological examination revealed significant ataxia and anisocoria. A posterior fossa heterogeneous mass with calcifications centered in the fourth ventricle was found, measuring approximately 5.0 × 4.7 × 4.2 cm (Figure 1). It was associated with severe supratentorial hydrocephalus. There was no evidence of spinal dissemination. She underwent placement of a right frontal external ventricular drain followed by suboccipital craniotomy and resection of the mass, with subsequent chemoradiation.&lt;/p&gt;&lt;p&gt;Histologic sections revealed a high-grade neoplasm with complex morphology. Some areas showed definite embryonal morphology with densely packed small cells with high nuclear/cytoplasmic ratio and brisk mitotic activity (Box 1, Figure 2A). The majority of the remaining tumor showed a mixture of haphazardly arranged spindled cell bundles with abundant eosinophilic cytoplasm and striations, typical of skeletal muscle differentiation (Figure 2B), and relatively mature neurons within a neuropil matrix, indicative of advanced neuronal differentiation (Figure 2C).&lt;/p&gt;&lt;p&gt;By immunohistochemistry (IHC), synaptophysin was positive in the embryonal component and areas with neuronal differentiation. Positive YAP1 stain was present and limited to the tumor cells with feature of skeletal muscle (Figure 2D). GAB1 stain was negative (Figure 2E), and beta-catenin expression was cytoplasmic (Figure 2F). Desmin, myogenin, and MyoD1 showed positivity in regions of skeletal muscle differentiation (Figure 2G,H). GFAP staining was largely confined to reactive astrocytes, while OLIG2 was negative. INI1 and BRG1 expressions were retained in the tumor cells. The IHC profile confirmed the morphological impression of medullomyoblastoma [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Chromosomal microarray and a Neuro-Oncology targeted next generation sequencing (NGS) panel were performed. The tumor showed partial gain of 1q and gain of chromosome 8, and harbored &lt;i&gt;KBTBD4&lt;/i&gt; (p.R313_W315delinsGSATMR) and &lt;i&gt;SMARCA4&lt;/i&gt; (p.R1189Q) pathogenic mutations. Two variants of uncertain significance (VUS) on &lt;i&gt;PDGFRA&lt;/i&gt; (p.R293H) and &lt;i&gt;NTRK1&lt;/i&gt; (p.V321M) were also present. These findings were most consistent with a non-WNT/non-SHH group 3/ group 4 medulloblastoma, favoring subgroup 2 [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Whole-genome methylation analysis performed at the Pathology Laboratory, National Cancer Institute using the Bethesda version 2 classifier yielded a “no match” result but suggested that the tumor belonged to the medulloblastoma family (Confidence Score [CS] = 0.909). Dimensionality reduction using UMAP (uniform manifold approximation and projection) positioned the tumor within a region enriched with medulloblastomas group 3/group 4, subgroup 2 (Figure 2I). Using the St. Jude methylation classifier, the tumor matched to group 3/group 4 medulloblastoma, subgroup 2, with high ","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483214","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 young man with multifocal brainstem leptomeningeal disease","authors":"Burana Khiankaew,&nbsp;Pornphan Sae-Sim,&nbsp;Pichet Termsarasab,&nbsp;Oranan Tritanon,&nbsp;Theeraphol Panyaping,&nbsp;Paisarn Boonsakan,&nbsp;Vichan Peonim,&nbsp;Virawudh Soontornniyomkij","doi":"10.1111/bpa.70026","DOIUrl":"10.1111/bpa.70026","url":null,"abstract":"&lt;p&gt;A 19-year-old man presented with right eye ptosis, horizontal binocular diplopia, and right facial paresthesia. Neurological examination was consistent with right third, fourth, fifth, and sixth cranial neuropathies. Head MR imaging revealed multifocal leptomeningeal enhancement along bilateral cranial nerves and an enhancing mass at the right-sided prepontine cistern (Figure 1A). Chest and abdominal CT scans showed no significant abnormalities.&lt;/p&gt;&lt;p&gt;Three months later, he developed progressive bilateral lower extremity weakness. Spine MR imaging revealed diffuse leptomeningeal enhancement of the spinal cord and cauda equina, and enhancing intramedullary lesions at dorsal T4 and right-sided T10 thoracic levels (Figure 1B). Follow-up head MR imaging showed progressive leptomeningeal enhancement and newly developed ependymal enhancement in the fourth ventricle, frontal horns of bilateral lateral ventricles, and septum pellucidum.&lt;/p&gt;&lt;p&gt;An initial biopsy from the prepontine mass showed lymphohistiocytic proliferation with atypical cells, which, alongside immunohistochemical (IHC) testing, favored a benign histiocytic lesion. A bone marrow biopsy was negative for malignancy. Some cerebrospinal fluid (CSF) analyses revealed atypical mononuclear cells. A subsequent biopsy via L2 lumbar laminectomy showed lymphohistiocytic proliferation, comprising atypical histiocytes (positive for CD163 and CD68/PG-M1; negative for S100, CD1a, and ALK/ALK1/D5F3), together with Ki-67-positive atypical cells, small CD3-positive T cells, and small CD20-positive B cells (Figure 2A). In-situ hybridization (ISH) for Epstein–Barr virus early RNA (EBER) was negative.&lt;/p&gt;&lt;p&gt;Given the relentless clinical and radiological progression, a tentative diagnosis of malignant histiocytosis was made. The patient had been treated with multiple courses of high-dose methotrexate-based chemotherapy but showed negligible neurological improvement. He subsequently developed the neurogenic bladder with recurrent urinary tract infections and later obstructive hydrocephalus. Eventually, he received comfort care and died 33 months after the initial presentation.&lt;/p&gt;&lt;p&gt;At autopsy, the central nervous system (CNS) showed an infiltrative neoplasm extensively involving the craniospinal leptomeninges and ventricular system and invading the cranial nerves, spinal nerve roots, cauda equina, subpial brain/spinal cord parenchyma, and subependymal brain parenchyma (Box 1, Figure 2B). The non-cohesive large neoplastic cells had pleomorphic vesicular/hyperchromatic nuclei, prominent nucleoli, and abundant pale-eosinophilic cytoplasm (Figure 2C). There was high mitotic activity, multinucleated cell formation, hemophagocytic activity, apoptosis, and focal necrosis.&lt;/p&gt;&lt;p&gt;On IHC testing, most of the neoplastic cells were positive for CD163 (Figure 2D) and CD68/PG-M1 (Figure 2E). The neoplastic cells were negative for lysozyme, myeloperoxidase, CD1a, CD3, CD4, CD20, CD21, CD30, CD45/LCA, CD123, ALK/ALK1/D5F3,","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367828","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}