Brain Pathology最新文献

{"title":"Resource availability for CNS tumor diagnostics in the Asian Oceanian region: A survey by the Asian Oceanian Society of Neuropathology committee for Adapting Diagnostic Approaches for Practical Taxonomy in Resource-Restrained Regions (AOSNP-ADAPTR)","authors":"Chitra Sarkar,&nbsp;Shilpa Rao,&nbsp;Vani Santosh,&nbsp;Maysa Al-Hussaini,&nbsp;Sung Hye Park,&nbsp;Tarik Tihan,&nbsp;Michael E. Buckland,&nbsp;Ho-Keung Ng,&nbsp;Takashi Komori","doi":"10.1111/bpa.13329","DOIUrl":"10.1111/bpa.13329","url":null,"abstract":"<p>The shift toward a histo-molecular approach in World Health Organization classification of central nervous system tumors (WHO CNS5) emphasizes the critical role of molecular testing, such as next-generation sequencing (NGS) and DNA methylation profiling, for accurate diagnosis. However, implementing these advanced techniques is particularly challenging in resource-constrained countries. To address this, the Asian Oceanian Society of Neuropathology committee for Adapting Diagnostic Approaches for Practical Taxonomy in Resource-Restrained Regions (AOSNP-ADAPTR) was initiated to help pathologists in resource-limited regions to implement WHO CNS5 diagnoses using simpler diagnostic tools, mainly immunohistochemistry. An online survey by this group assessed the in-house/local availability of diagnostic resources and outsourcing capabilities across the Asian Oceanian region, covering 19 countries. Of 318 responding centers, the availability of molecular techniques in-house/locally was limited in lower middle-income countries (LMICs), with 29% having fluorescence in situ hybridization, 10.7% Sanger sequencing, and only 9.4% NGS. DNA methylation was largely unavailable in-house/locally in of LMICs, while in the whole region, its availability stood at a meager 4.4%. Though outsourcing for all diagnostic tests was an easily accessible alternative, outsourcing for NGS and DNA methylation was uncommon because of the financial burden on patients being a significant obstacle. The survey categorized centers into five resource levels (RLs) based on the in-house/local access to diagnostic techniques, which highlighted the variability and disparity in diagnostic capabilities across the region. High-income countries had 80% of centers with advanced RL IV, V resources, in contrast to LMICs, where 70.5% of centers fell into RL I–III. This comprehensive evaluation emphasizes the need for tailored resource level guidelines, with the aim of improving diagnostic accuracy and treatment as well as advocating better healthcare infrastructure in resource-constrained areas. However, the survey's reliance on responses from better-resourced centers may underestimate challenges in lower-resource settings, stressing the need for broader outreach and support.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13329","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000543","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":"Fetal growth restriction adversely impacts trajectory of hippocampal neurodevelopment and function","authors":"Ingrid Dudink,&nbsp;Amy E. Sutherland,&nbsp;Margie Castillo-Melendez,&nbsp;Elham Ahmadzadeh,&nbsp;Tegan A. White,&nbsp;Atul Malhotra,&nbsp;Harold A. Coleman,&nbsp;Helena C. Parkington,&nbsp;Justin M. Dean,&nbsp;Yen Pham,&nbsp;Tamara Yawno,&nbsp;Tara Sepehrizadeh,&nbsp;Graham Jenkin,&nbsp;Emily J. Camm,&nbsp;Beth J. Allison,&nbsp;Suzanne L. Miller","doi":"10.1111/bpa.13330","DOIUrl":"10.1111/bpa.13330","url":null,"abstract":"<p>The last pregnancy trimester is critical for fetal brain development but is a vulnerable period if the pregnancy is compromised by fetal growth restriction (FGR). The impact of FGR on the maturational development of neuronal morphology is not known, however, studies in fetal sheep allow longitudinal analysis in a long gestation species. Here we compared hippocampal neuron dendritogenesis in FGR and control fetal sheep at three timepoints equivalent to the third trimester of pregnancy, complemented by magnetic resonance image for brain volume, and electrophysiology for synaptic function. We hypothesized that the trajectory of hippocampal neuronal dendrite outgrowth would be decreased in the growth-restricted fetus, with implications for hippocampal volume, connectivity, and function. In control animals, total dendrite length increased with advancing gestation, but not in FGR, resulting in a significantly reduced trajectory of dendrite outgrowth in FGR fetuses for total length, branching, and complexity. Ex vivo electrophysiology analysis shows that paired-pulse facilitation was reduced in FGR compared to controls for cornu ammonis 1 hippocampal outputs, reflecting synaptic dysfunction. Hippocampal brain-derived neurotrophic factor density decreased over late gestation in FGR fetuses but not in controls. This study reveals that FGR is associated with a significant deviation in the trajectory of dendrite outgrowth of hippocampal neurons. Where dendrite length significantly increased over the third trimester of pregnancy in control brains, there was no corresponding increase over time in FGR brains, and the trajectory of dendrite outgrowth in FGR offspring was significantly reduced compared to controls. Reduced hippocampal dendritogenesis in FGR offspring has severe implications for the development of hippocampal connectivity and long-term function.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13330","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944968","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":"Protective role of Angiogenin in muscle regeneration in amyotrophic lateral sclerosis: Diagnostic and therapeutic implications","authors":"Paola Fabbrizio,&nbsp;Sharada Baindoor,&nbsp;Cassandra Margotta,&nbsp;Junyi Su,&nbsp;Elena P. Morrissey,&nbsp;Ina Woods,&nbsp;Marion C. Hogg,&nbsp;Sara Vianello,&nbsp;Morten T. Venø,&nbsp;Jørgen Kjems,&nbsp;Gianni Sorarù,&nbsp;Caterina Bendotti,&nbsp;Jochen H. M. Prehn,&nbsp;Giovanni Nardo","doi":"10.1111/bpa.13328","DOIUrl":"10.1111/bpa.13328","url":null,"abstract":"<p>Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease with no effective treatments, in part caused by variations in progression and the absence of biomarkers. Mice carrying the SOD1G93A transgene with different genetic backgrounds show variable disease rates, reflecting the diversity of patients. While extensive research has been done on the involvement of the central nervous system, the role of skeletal muscle remains underexplored. We examined the impact of angiogenin, including its RNase activity, in skeletal muscles of ALS mouse models and in biopsies from ALS patients. Elevated levels of angiogenin were found in slowly progressing mice but not in rapidly progressing mice, correlating with increased muscle regeneration and vascularisation. In patients, higher levels of angiogenin in skeletal muscles correlated with milder disease. Mechanistically, angiogenin promotes muscle regeneration and vascularisation through satellite cell-endothelial interactions during myogenesis and angiogenesis. Furthermore, specific angiogenin-derived tiRNAs were upregulated in slowly progressing mice, suggesting their role in mediating the effects of angiogenin. These findings highlight angiogenin and its tiRNAs as potential prognostic markers and therapeutic targets for ALS, offering avenues for patient stratification and interventions to mitigate disease progression by promoting muscle regeneration.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13328","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892262","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":"","doi":"10.1111/bpa.13320","DOIUrl":"https://doi.org/10.1111/bpa.13320","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13320","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143118977","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":"Potentiating microglial efferocytosis by MFG-E8 improves survival and neurological outcome after successful cardiopulmonary resuscitation in mice","authors":"Kunxue Zhang,&nbsp;Yuzhen Zhang,&nbsp;Zhentong Li,&nbsp;Jiancong Chen,&nbsp;Yuan Chang,&nbsp;Yongchuan Li,&nbsp;Shuxin Zeng,&nbsp;Sifan Pan,&nbsp;Suyue Pan,&nbsp;Kaibin Huang","doi":"10.1111/bpa.13327","DOIUrl":"10.1111/bpa.13327","url":null,"abstract":"<p>Brain injury represents the leading cause of mortality and disability after cardiopulmonary resuscitation (CPR) from cardiac arrest (CA), in which the accumulation of dying cells aggravate tissue injury by releasing proinflammatory intracellular components. Microglia play an essential role in maintaining brain homeostasis via milk fat globule epidermal growth factor 8 (MFG-E8)-opsonized efferocytosis, the engulfment of dying cells and debris. This study investigates whether potentiating microglia efferocytosis by MFG-E8 provides neuroprotection after CA/CPR. After 8-minute asphyxial CA/CPR, male adult C57BL/6J mice were randomly assigned to receive recombinant mouse MFG-E8 (rmMFG-E8) or vehicle. We evaluated the survival and neurological deficits of mice, along with histological damages, phagocytosis index of dying cells, and microglia polarization. A transcriptome analysis was conducted to explore the downstream molecules modulated by MFG-E8. In mice resuscitated from CA, rmMFG-E8 administration significantly enhanced the efferocytosis of apoptotic cells by microglia, improved the survival and neurological function of mice, and attenuated neuropathological injuries. Additionally, rmMFG-E8 induced a prominent alteration in microglial gene expression and promoted a shift from a proinflammatory phenotype to an anti-inflammatory phenotype. Moreover, rmMFG-E8 treatment induced up-regulation of interferon regulatory factor 7 (IRF7), and IRF7 gene silencing largely reversed the neuroprotective effects of rmMFG-E8. This study demonstrates that rmMFG-E8 improves survival and neurological outcomes after CA/CPR by enhancing microglial efferocytosis and reshaping the inflammatory microenvironment in brain tissue. Potentiating MFG-E8 is a promising strategy to combat post-CA brain injury.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13327","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881326","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":"Extra-axial mass in a 72-year-old woman","authors":"S. Rima,&nbsp;B. N. Nandeesh,&nbsp;Mangalkumar Rachatte,&nbsp;Anil Pande","doi":"10.1111/bpa.13325","DOIUrl":"10.1111/bpa.13325","url":null,"abstract":"&lt;p&gt;A 72-year-old lady presented with complaints of slurring of speech, loss of appetite, sleep disturbance for the past 1 month. Magnetic resonance imaging brain showed a large extra-axial space occupying lesion noted along left frontal convexity, measuring 47 × 70 × 36 mm. The lesion was hyperintense on T2 and hypointense on T1 and showed diffusion restriction and contrast enhancement (Figure 1). Cerebrospinal fluid (CSF) cleft sign and buckling of adjacent white matter (anterior) and pial vessels were noted around the lesion. The lesion showed few prominent intralesional flow voids. The overall imaging features favored a meningioma. She underwent left frontoparietal craniotomy and Simpson's Grade II excision of lesion (Box 1).&lt;/p&gt;&lt;p&gt;Histopathological examination showed a meningothelial tumor composed of neoplastic meningothelial cells with mild nuclear anisonucleosis, arranged as whorls and syncytium. Embedded and admixed within this meningothelial neoplasm were deposits from an epithelial neoplasm comprising of tumor cells arranged in acini of varying sizes and papillae (Figure 2A,B and Box 1). These cells were polygonal with vesicular nuclei, visible nucleoli and moderate amounts of eosinophilic cytoplasm. Mitoses were noted within both the components, and atypical mitotic figures were seen in the epithelial component (Figure 2C). The mitotic activity in the meningothelial component was 1–2/10 high power fields. On immunohistochemistry, the meningioma component was positive for Vimentin, EMA (epithelial membrane antigen), and SSTR2A (somatostatin receptor 2A) (Figure 2D). The epithelial component was positive for EMA, CK (cytokeratin; Figure 2E) and CK7. TTF-1 (thyroid transcription factor) showed diffuse moderate to strong positivity in the epithelial component, indicating a primary carcinoma from lung or thyroid origin (Figure 2F). The tumor cells were negative for CK20. MIB1 labeling index was 5%–6% in the meningothelial component and 20%–25% in the epithelial component.&lt;/p&gt;&lt;p&gt;Metastatic adenocarcinoma, consistent with lung primary to transitional meningioma (CNS WHO grade 1).&lt;/p&gt;&lt;p&gt;This case is an example of tumor-to-tumor metastasis (TTM). Tumor-to-meningioma metastasis (TTMM) refers to a phenomenon where a tumor metastasizes to a meningioma, also known as intrameningioma metastasis. It is important to distinguish TTM from collision tumors. Collision tumors are tumors that grow adjacent to each other and infiltrates into one another. The first tumor-to-tumor phenomenon was reported in 1902 by Berent. The criteria for TTM proposed by L.V. Campbell are: at least two primary tumors must exist; the host tumor must be a true neoplasm; the metastatic focus must show established growth inside the host tumor, and not be of contiguous growth; the host tumor cannot be a lymph node involved in leukemia or lymphoma [&lt;span&gt;1&lt;/span&gt;]. The most common tumors associated with TTMM are breast carcinoma and lung carcinoma. Other tumors associated with TTMM","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 2","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13325","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876252","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":"Molecular profile of adult primary leptomeningeal gliomatosis aligns with glioblastoma, IDH-wildtype","authors":"Yi Zhu,&nbsp;Darin D. Carabenciov,&nbsp;Derek R. Johnson,&nbsp;Jorge A. Trejo-Lopez,&nbsp;Aivi T. Nguyen,&nbsp;Aditya Raghunathan,&nbsp;Giuseppe Lanzino,&nbsp;Cristiane M. Ida,&nbsp;Cinthya J. Zepeda-Mendoza,&nbsp;Surendra Dasari,&nbsp;Emilie Russler-Germain,&nbsp;Sonika Dahiya,&nbsp;Martha Quezado,&nbsp;Kenneth Aldape,&nbsp;Caterina Giannini","doi":"10.1111/bpa.13326","DOIUrl":"10.1111/bpa.13326","url":null,"abstract":"<p>Adult primary leptomeningeal gliomatosis (PLG) is a rare, rapidly progressive and fatal disease characterized by prominent leptomeningeal infiltration by a glial tumor without an identifiable parenchymal mass. The molecular profile of adult PLG has not been well-characterized. We report the clinical, pathological, and molecular findings of six adult PLG patients (five males and one female), median age 58 years. All cases exhibited pathological leptomeningeal enhancement at presentation. Leptomeningeal biopsy was diagnostic in five (of six) cases, revealing infiltration by an astrocytic glioma with mitotic activity, lacking microvascular proliferation or necrosis. One case was diagnosed at autopsy. All tumors were IDH-wildtype, with five harboring <i>TERT</i> promoter mutations. Additional mutations identified were <i>PTEN</i> in one case, <i>TP53</i> in two cases, and <i>NF1</i> in two cases. A chromosome profile with +7/−10 was found in four cases, whereas the remaining two showed either chromosome 7 or 7p gain only. Four cases showed chromosome 9p loss with <i>CDKN2A/B</i> homozygous deletion, one case showed hemizygous <i>CDKN2A/B</i> loss, and one case showed intact chromosome 9 and <i>CDK4/GLI1</i> amplification. DNA methylation profiling was performed in four cases and revealed a match to glioblastoma (GBM) family and mesenchymal typical class with high confidence scores in two cases; the other two cases showed only suggestive combined scores for GBM family and mesenchymal atypical class. The molecular profile of all cases closely aligned with that of adult-type GBM, IDH-wildtype, CNS WHO grade 4. All patients succumbed to the disease. In five cases with extensive leptomeningeal disease at diagnosis, the course was rapid, with median survival of 24 days following palliative care. Only one case, with relatively localized disease at diagnosis, received chemoradiation therapy and survived 535 days, raising the possibility that early diagnosis and timely treatment could improve outcome. A detailed list of previously reported cases is provided in a supplementary table.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13326","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845866","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":"Reply to letter by Melmed et al.","authors":"C. Villa,&nbsp;M. F. Birtolo,&nbsp;L. G. Perez-Rivas,&nbsp;A. Righi,&nbsp;G. Assié,&nbsp;B. Baussart,&nbsp;S. Asioli","doi":"10.1111/bpa.13324","DOIUrl":"10.1111/bpa.13324","url":null,"abstract":"&lt;p&gt;We would like to thank Professor Melmed and colleagues for commenting on our review recently published in Brain Pathology and highlighting areas for improvement.&lt;/p&gt;&lt;p&gt;This invited review is part of a Mini Symposium on the WHO Classification of Pituitary Tumors, covering an overview of the 5th Edition with comparison between CNS5 and ENDO5, a review on practical approaches of diagnosing PitNET/adenomas according to cell lineage, our review on grading and staging, an update on aggressive and metastatic PitNETs and a review on posterior pituitary and rare pituitary tumors. These manuscripts are available online [&lt;span&gt;1-4&lt;/span&gt;] before the publication in a special format, which will include an introduction to the issue covering also the PANOMEN consensus. In this respect, the letter to the Editor does not take into consideration the other manuscripts and is premature. The Editor and authors of the four reviews have taken great care in ensuring that content was accurate and that no overlap and repetitions occurred.&lt;/p&gt;&lt;p&gt;Our review on grading and staging of pituitary tumors included 112 references and priorities original studies providing new insights or proof of concept on well-characterized cohorts as well as systematic reviews. This approach was adopted to cite studies relevant to the focus of the manuscript and avoid unnecessary repetition and self-citation.&lt;/p&gt;&lt;p&gt;The clinical classification of pituitary neoplasms proposed by the PANOMEN workshop [&lt;span&gt;5&lt;/span&gt;] represents a promising and innovative approach that has the potential to be adopted widely once validated by independent prospective studies. We hope that the IARC-WHO working group will consider an integrated multidisciplinary classification that acknowledges the recently proposed workflows once thoroughly validated.&lt;/p&gt;&lt;p&gt;Currently, the only viable alternative to the WHO classification for a staging and/or classification system is the five-tiered prognostic classification [&lt;span&gt;6&lt;/span&gt;] that has already been tested by several independent cohorts on more than 3000 patients.&lt;/p&gt;&lt;p&gt;The low rate of histologically confirmed pituitary tumors as indicated in the Central Brain Tumor Registry of the United States (CBTRUS) statistical report [&lt;span&gt;7&lt;/span&gt;] does not account for the large number of pituitary tumors that are followed up and/or medically treated and therefore lack histopathologic confirmation. Indeed, as stated in the report and in the CBTRUS website: “The Central Brain Tumor Registry of the United States (CBTRUS) is a not-for-profit research corporation, recognized by the international research community as the premier resource for annual histology-specific statistical information for all primary brain and other CNS tumors in the United States.”&lt;/p&gt;&lt;p&gt;The change of nomenclature from adenoma to PitNET will favor the registration of adenohypophyseal tumors in NET/NEN Cancer Registries, allowing for the collection of more accurate epidemiological and follow-up data.&lt;/p&gt;&lt;p&gt;As ","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833901","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":"Neuropathological and cerebrospinal fluid correlates of choroid plexus inflammation in progressive multiple sclerosis","authors":"R. Magliozzi,&nbsp;S. Hametner,&nbsp;M. Mastantuono,&nbsp;A. Mensi,&nbsp;M. Karimian,&nbsp;L. Griffiths,&nbsp;L. M. Watkins,&nbsp;A. Poli,&nbsp;G. M. Berti,&nbsp;E. Barusolo,&nbsp;B. Bellini,&nbsp;S. Rossi,&nbsp;D. Gveric,&nbsp;J. A. Stratton,&nbsp;K. Akassoglou,&nbsp;S. Magon,&nbsp;R. Nicholas,&nbsp;R. Reynolds,&nbsp;O. W. Howell,&nbsp;S. Monaco","doi":"10.1111/bpa.13322","DOIUrl":"10.1111/bpa.13322","url":null,"abstract":"<p>Among the intrathecal inflammatory niches where compartmentalized inflammation persists and plays a pivotal role in progressive multiple sclerosis (MS), choroid plexus (CP) has recently received renewed attention. To better characterize the neuropathological/molecular correlates of CP in progressive MS and its potential link with other brain inflammatory compartments, such as perivascular spaces and leptomeninges, the levels, composition and phenotype of CP immune infiltration in lateral ventricles of the hippocampus were examined in 40 post-mortem pathologically confirmed MS and 10 healthy donors, using immunochemistry/immunofluorescence and in-situ sequencing. Significant inflammation was detected in the CP of 21 out of the 40 MS cases (52%). The degree of CP inflammation was found correlated with: number of CP macrophages (R: 0.878, <i>p =</i> 1.012 x 10^-13) and high frequency of innate immune cells expressing the markers MHC-class II, CD163, CD209, CD11c, TREM2 and TSPO; perivascular inflammation (R: 0.509, <i>p =</i> 7.921 x 10^-4), and less with meningeal inflammation (R: 0.365, <i>p =</i> 0.021); number of active lesions (R: 0.51, p: 3.524 x 10^-5). However, it did not significantly correlate with any clinical/demographic characteristics of the examined population. In-situ sequencing analysis of gene expression in the CP of 3 representative MS cases and 3 controls revealed regulation of inflammatory pathways mainly related to ‘type 2 immune response’, ‘defense to infections’, ‘antigen processing/presentation’. Analysis of 78 inflammatory molecules in paired post-mortem CSF, the levels of fibrinogen (R: 0.640, <i>p =</i> 8.752 x 10^-6), PDGF-bb (R: 0.470, <i>p =</i> 0.002), CXCL13 (R: 0.428, <i>p =</i> 0.006) and IL15 (R: 0.327, <i>p =</i> 0.040) were correlated with extent of CP inflammation. Elevated fibrinogen and complement deposition were found in CP and in underlying subependymal periventricular areas, according to “surface-in” gradient associated with concomitant prominent microglia activation. CP inflammation, predominantly characterized by innate immunity, represents another key determinant of intrathecal, compartmentalised inflammation persisting in progressive MS, which may be possibly activated by fibrinogen and influence periventricular pathology, even without substantial association with clinical features.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13322","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766340","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 5th Edition of the WHO Classification of Pituitary Tumors: Strengths and limitations","authors":"M. Beatriz Lopes","doi":"10.1111/bpa.13323","DOIUrl":"10.1111/bpa.13323","url":null,"abstract":"<p>The 5th Edition of the World Health Organization (WHO) Classification of Tumors of the Pituitary Gland, initially released as a chapter in Central Nervous System Tumors Book (CNS5) in 2021 [<span>1</span>] and then modified and revised in Endocrine and Neuroendocrine Tumors Book (ENDO5) (still online) in 2022 [<span>2</span>], has provided the community with a framework for classification of pituitary tumors. For the most common tumors involving the gland, the pituitary adenomas (now pituitary neuroendocrine tumors or PitNETs), the classification has endorsed the experience since ENDO4 of a cell lineage-based classification with description of distinct types and subtypes of tumors.</p><p>In this Mini-Symposium, four articles will discuss the strengths and weaknesses of the WHO pituitary tumors classification focusing on proposals for future classifications.</p><p>Goyal-Honavar and Chacko [<span>3</span>] discuss the challenges of a histopathological classification based solely on immunohistochemistry (IHC) of pituitary hormones and transcription factors. Some of the challenges include lack of criteria for positivity by IHC expression, costs and availability of antibodies worldwide, and precise diagnostic criteria for new tumor types/subtypes that have emerged since the widespread adaptation of the classification system, in particular the so-called multilineage tumors.</p><p>Villa et al. [<span>4</span>] analyze the several steps for grading and staging of PitNETs/adenomas and the challenges of fitting pituitary tumors in the overall scheme of grading/staging of other neuroendocrine neoplasms/tumors (NEN/NETs) as intended by the WHO classification. Most significantly, the authors comment on the need for clinical, biochemical, and radiological integration with the histopathology in a clinico-pathological classification of the tumors.</p><p>The discussion of aggressive PitNETs/adenomas is examined by Casar-Borota et al. [<span>5</span>] that dissect the clinical and pathological undertakings of diagnosing tumors that are beyond the so-called “benign adenoma,” including locally invasive, clinically aggressive, and metastatic tumors. The authors discuss the clinical, pathological, and molecular aspects of these more aggressive tumors and potential predictor factors for tumor recurrence and progression. They also provide a critical analysis of the controversial ICD-O coding system applied to PitNETs/adenomas in ENDO5.</p><p>Still focusing on the new WHO classification, Roncaroli and Giannini [<span>6</span>] discuss another group of pituitary tumors, the non-neuroendocrine tumors, focusing on the TTF-1 expressing tumors of the posterior pituitary and infundibulum, the newly described tumor with the proposed name of Primary Papillary Epithelial Tumor of the Sella (that also expresses nuclear TTF-1), and the rare sellar atypical teratoid/rhabdoid tumor (AT/RT). The authors describe in detail these entities clinical, pathological and molecular aspects,","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766345","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}