Brain Pathology最新文献

{"title":"Molecular profile of adult primary leptomeningeal gliomatosis aligns with glioblastoma, IDH-wildtype.","authors":"Yi Zhu, Darin D Carabenciov, Derek R Johnson, Jorge A Trejo-Lopez, Aivi T Nguyen, Aditya Raghunathan, Giuseppe Lanzino, Cristiane M Ida, Cinthya J Zepeda-Mendoza, Surendra Dasari, Emilie Russler-Germain, Sonika Dahiya, Martha Quezado, Kenneth Aldape, Caterina Giannini","doi":"10.1111/bpa.13326","DOIUrl":"https://doi.org/10.1111/bpa.13326","url":null,"abstract":"<p><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 TERT promoter mutations. Additional mutations identified were PTEN in one case, TP53 in two cases, and NF1 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 CDKN2A/B homozygous deletion, one case showed hemizygous CDKN2A/B loss, and one case showed intact chromosome 9 and CDK4/GLI1 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":" ","pages":"e13326"},"PeriodicalIF":5.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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, S Hametner, M Mastantuono, A Mensi, M Karimian, L Griffiths, L M Watkins, A Poli, G M Berti, E Barusolo, B Bellini, S Rossi, D Gveric, J A Stratton, K Akassoglou, S Magon, R Nicholas, R Reynolds, O W Howell, S Monaco","doi":"10.1111/bpa.13322","DOIUrl":"https://doi.org/10.1111/bpa.13322","url":null,"abstract":"<p><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, p = 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, p = 7.921 x 10^-4), and less with meningeal inflammation (R: 0.365, p = 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, p = 8.752 x 10^-6), PDGF-bb (R: 0.470, p = 0.002), CXCL13 (R: 0.428, p = 0.006) and IL15 (R: 0.327, p = 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":" ","pages":"e13322"},"PeriodicalIF":5.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"&lt;p&gt;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 [&lt;span&gt;1&lt;/span&gt;] and then modified and revised in Endocrine and Neuroendocrine Tumors Book (ENDO5) (still online) in 2022 [&lt;span&gt;2&lt;/span&gt;], 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.&lt;/p&gt;&lt;p&gt;In this Mini-Symposium, four articles will discuss the strengths and weaknesses of the WHO pituitary tumors classification focusing on proposals for future classifications.&lt;/p&gt;&lt;p&gt;Goyal-Honavar and Chacko [&lt;span&gt;3&lt;/span&gt;] 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.&lt;/p&gt;&lt;p&gt;Villa et al. [&lt;span&gt;4&lt;/span&gt;] 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.&lt;/p&gt;&lt;p&gt;The discussion of aggressive PitNETs/adenomas is examined by Casar-Borota et al. [&lt;span&gt;5&lt;/span&gt;] 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.&lt;/p&gt;&lt;p&gt;Still focusing on the new WHO classification, Roncaroli and Giannini [&lt;span&gt;6&lt;/span&gt;] 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}

{"title":"A broader outlook is required to stage and classify pituitary neoplasms for patient care","authors":"Shlomo Melmed,&nbsp;Maria Fleseriu,&nbsp;John A. H. Wass,&nbsp;Ken K. Y. Ho","doi":"10.1111/bpa.13321","DOIUrl":"10.1111/bpa.13321","url":null,"abstract":"&lt;p&gt;Synthesis of the current literature in a robust review is important for advancing science as it provides updated objective evidence-based information to the reader [&lt;span&gt;1&lt;/span&gt;]. Strong and fair reviews should serve as a credible resource for the reader, marshaling strengths and weaknesses of available evidence on a particular topic. Evidence sources should include all relevant current literature, particularly publications in high-impact journals. The review should thus offer a balanced appraisal of areas of agreement and controversy, highlight unanswered questions, and present opportunities for future research.&lt;/p&gt;&lt;p&gt;Regrettably, the Invited Review from Villa et al. [&lt;span&gt;2&lt;/span&gt;] on the grading and staging system for pituitary neuroendocrine tumors (PitNETs) based on the WHO Classification of Endocrine and Neuroendocrine Tumors falls short of these criteria for a fair and balanced review. The authors contend that the review “illustrates the main issues involved in establishing a grading and a staging system, as well as alternative systems.” However, it does not mention a body of recent literature devoted to the WHO's controversial classification of pituitary adenomas as PitNETs [&lt;span&gt;3, 4&lt;/span&gt;]. They advocate using a histo-molecular approach but do not address a consensus recommendation from the international multidisciplinary PANOMEN Workshop for a comprehensive pituitary adenoma classification embodying histo-molecular markers [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Unambiguous communication of medical advances to the scientist and practitioner should aim to enhance clinical care. However, the utility of new classification proposals may be impaired by subjective opinions when not subjected to informed peer review, and may harm the foundation of medical communication. Impartial criteria should be applied as objective determinants of a new classification. These may include interdisciplinary clinical relevance, as well as universal physician and patient acceptance.&lt;/p&gt;&lt;p&gt;The PANOMEN classification was proposed by members of professional societies representing clinical disciplines who care for patients with these lesions, including the Endocrine Society, Pituitary Society, European Society of Endocrinology, International Society of Pituitary Surgeons, American Association of Clinical Endocrinology, and US and Canadian Academy of Pathology, and endorsed by patient support organizations [&lt;span&gt;5&lt;/span&gt;]. Scientific peer-reviewed evidence was collected and underwent robust multidisciplinary analysis and discussion prior to peer review and publication. These elements are glaringly lacking in the formulation of the WHO classification. Indeed, a recent Commentary [&lt;span&gt;6&lt;/span&gt;] highlights the need for this type of multidisciplinary approach and points to flaws in the WHO classification that could engender patient mismanagement through misuse of inappropriate nomenclature in the clinic.&lt;/p&gt;&lt;p&gt;Unlike the histology-based WHO classification, the PANOMEN class","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692627","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":"Clinico-sero-pathological characteristics of anti-Ha antisynthetase syndrome","authors":"Bing Zhao,&nbsp;Ying Hou,&nbsp;Kai Shao,&nbsp;XiaoTian Ma,&nbsp;YaPing Yan,&nbsp;Jian-Qiang Lu,&nbsp;Wei Li,&nbsp;ChuanZhu Yan,&nbsp;LiNing Zhang,&nbsp;TingJun Dai","doi":"10.1111/bpa.13319","DOIUrl":"10.1111/bpa.13319","url":null,"abstract":"<p>To define the clinical, serological, and muscle histopathological characteristics, as well as treatment outcomes, of patients with anti-Ha antibody. We performed a retrospective analysis of clinical, serological, and pathological data and long-term treatment outcomes of anti-Ha patients between January 2005 and July 2023 at our center. Anti-Ha antibody was identified by immunoblot and reconfirmed by immunoprecipitation. Of the 570 patients with idiopathic inflammatory myopathies, 17 (3.0%) were found to be anti-Ha positive, of whom 5 (29.4%) were also positive for another myositis-specific antibody (MSA). All patients with anti-Ha antibody as the single MSA (12/17, 70.6%) had clinical and histopathological evidence of muscle damage. Skin lesions were identified in nine of them (75%), while both interstitial lung disease and Raynaud's phenomenon were only seen in four patients. A necrotizing myopathy without a perifascicular pattern was the most common pathological manifestation (50%). Perifascicular necrosis (PFN) and myofiber major histocompatibility complex class-II expression were observed only in one and four patients, respectively. Muscle weakness relapse was reported in five patients, and skin rashes worsening were observed in one patient. Most of the anti-Ha patients (66.7%) finally achieved a favorable outcome at last follow-up. Anti-Ha antibody might not be as rare as previously thought and may coexist with other MSAs. Muscle damage is the most common manifestation in anti-Ha patients, while extra-muscular symptoms except for the cutaneous manifestations are unusual. The histopathological features varied with a predominance of necrotizing myopathy without PFN. These patients often finally had favorable outcomes, although relapses often occur.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 3","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13319","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667324","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 prevalence of chronic traumatic encephalopathy in a historical epilepsy post-mortem collection","authors":"Maritchka Ryniejska,&nbsp;Hanaa El-Hachami,&nbsp;Alicja Mrzyglod,&nbsp;Joan Liu,&nbsp;Maria Thom","doi":"10.1111/bpa.13317","DOIUrl":"10.1111/bpa.13317","url":null,"abstract":"<p>Previous post-mortem epilepsy series showed phosphorylated tau (pTau) accumulation in relation to traumatic brain injury (TBI) rather than driven by seizure frequency. The Corsellis Epilepsy Collection, established in the mid-20th century, represents brain samples collected from patients living with a range of epilepsies from the 1880s to 1990s. Our aim was to interrogate this historical archive to explore relationships between epilepsy, trauma and tau pathology. AT8 immunohistochemistry for pTau was carried out in 102 cases (55% male, with mean age at death of 62 years) on frontal, temporal, amygdala, hippocampal and lesional cortical regions and evaluated using current NINDS criteria for chronic traumatic encephalopathy (CTE) and Braak staging with beta-amyloid, AT8-GFAP and other pTau markers (CP13, PHF1, AT100, AT180) in selected cases. CTE-neuropathologic change (CTE-NC) was identified in 15.7% and was associated with the presence of astroglial tau, a younger age of onset of epilepsy, evidence of TBI and institutionalisation for epilepsy compared to cases without CTE-NC, but not for seizure type or frequency. Memory impairment was noted in 43% of cases with CTE-NC, and a significantly younger age of death; more frequent reports of sudden and unexpected death (<i>p</i> &lt;0.05–0.001) were noted in cases with CTE-NC. In contrast, a higher Braak stage was associated with late-onset epilepsy and cognitive decline. Of note, 9% of cases showed no pTau, including cases with long epilepsy duration, poor seizure control and a history of prior TBI. In summary, this cohort includes patients with more severe and diverse forms of epilepsy, with CTE-NC observed more frequently than reported in non-epilepsy community-based studies (0%–8%) but lower than published series from contact sports participants (32%–87%). Although the literature does not report increased epilepsy occurring in CTE syndrome, our findings support an increased risk of CTE in epilepsy syndromes, likely primarily related to increased TBI.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 3","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13317","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615258","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":"Altered immune response is associated with sex difference in vulnerability to Alzheimer's disease in human prefrontal cortex","authors":"Huiying Wen,&nbsp;Youzhe He,&nbsp;Yuanchun Tang,&nbsp;Langjian Zhu,&nbsp;Quyuan Tao,&nbsp;Bufan Jin,&nbsp;Ting Luo,&nbsp;Yujie Peng,&nbsp;Yanrong Wei,&nbsp;Junjie Lei,&nbsp;Lifang Wang,&nbsp;Fan Wang,&nbsp;Fei Ling,&nbsp;Yue Gao,&nbsp;Lei Han","doi":"10.1111/bpa.13318","DOIUrl":"10.1111/bpa.13318","url":null,"abstract":"<p>Alzheimer's disease (AD) is a neurodegenerative disorder with a higher risk incidence in females than in males, and there are also differences in AD pathophysiology between sexes. The role of sex in the pathogenesis of AD may be crucial, yet the cellular and molecular basis remains unclear. Here, we performed a comprehensive analysis using four public transcriptome datasets of AD patients and age-matched control individuals in prefrontal cortex, including bulk transcriptome (295 females and 402 males) and single-nucleus RNA sequencing (snRNA-seq) data (224 females and 219 males). We found that the transcriptomic profile in female control was similar to those in AD. To characterize the key features associated with both the pathogenesis of AD and sex difference, we identified a co-expressed gene module that positively correlated with AD, sex, and aging, and was also enriched with immune-associated pathways. Using snRNA-seq datasets, we found that microglia (MG), a resident immune cell in the brain, demonstrated substantial differences in several aspects between sexes, such as an elevated proportion of activated MG, altered transcriptomic profile and cell–cell interaction between MG and other brain cell types in female control. Additionally, genes upregulated in female MG, such as <i>TLR2</i>, <i>MERTK</i>, <i>SPP1</i>, <i>SLA</i>, <i>ACSL1</i>, and <i>FKBP5</i>, had high confidence to be identified as biomarkers to distinguish AD status, and these genes also interacted with some approved drugs for treatment of AD. These findings underscore the altered immune response in female is associated with sex difference in susceptibility to AD, and the necessity of considering sex factors when developing AD biomarkers and therapeutic strategies, providing a scientific basis for further in-depth studies on sex differences in AD.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 3","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574909","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 pineal region mass in a 55-year-old female","authors":"Aaron McConeghey,&nbsp;Zied Abdullaev,&nbsp;Kenneth Aldape,&nbsp;Steven A. Moore,&nbsp;Osorio Lopes Abath Neto","doi":"10.1111/bpa.13315","DOIUrl":"10.1111/bpa.13315","url":null,"abstract":"&lt;p&gt;A 55-year-old female with headache was found on magnetic resonance imaging to have a 2.6 cm contrast enhancing, diffusion restricted pineal mass (Figure 1). Three months later, she presented to the emergency department with confusion, imbalance, headaches, body aches, fatigue, and elevated blood pressure. Physical exam showed bitemporal hemianopsia and a left fourth nerve paresis. Computed tomography imaging at that time revealed enlargement of the mass with peripheral calcification associated with ventriculomegaly and diffuse sulcal effacement, consistent with obstructive hydrocephalus (Figure 1 inset). Urgent external ventricular drain placement was performed resulting in improvement of symptoms. A surgical resection was then pursued. Intraoperatively, the mass showed evidence of prior hemorrhage and was noted to encase internal cerebral veins and the vein of Galen, preventing gross total resection. After a final diagnosis was reached, adjuvant treatment was planned with concurrent radiation therapy and chemotherapy with temozolomide. The patient is currently doing well at an early 3-month follow-up.&lt;/p&gt;&lt;p&gt;H&amp;E-stained sections revealed a markedly hypercellular tumor composed of small cells with high nuclear–cytoplasmic ratios, pleomorphic nuclei, abundant apoptotic bodies, focal areas of necrosis, and mitotic figures (Box 1, Figure 2A,B). Rosettes were not apparent. The immunophenotype of the neoplastic cells was consistent with an embryonal neoplasm: diffuse strong positivity for synaptophysin (Figure 2C), focal positivity for chromogranin A and neurofilament (not shown), and negative staining for OLIG2 (Figure 2C inset) and SALL4 (not shown). There was retained nuclear expression of INI-1 and BRG-1 (not shown). Ki-67 showed an elevated proliferative index (approximately 40%, Figure 2D).&lt;/p&gt;&lt;p&gt;DNA methylation profiling (Illumina MethylationEPIC) was performed and resulted in consensus matches in Heidelberg v12b6 and Bethesda v2 classifiers to the &lt;i&gt;pineoblastoma&lt;/i&gt;, &lt;i&gt;miRNA pathway altered&lt;/i&gt;, &lt;i&gt;group 1A&lt;/i&gt; methylation class with high confidence scores (greater than 0.9). Dimensionality reduction with Uniform Manifold Approximation and Projection (UMAP) placed the sample in the pineoblastoma family (Figure 2E). Copy number variation analysis derived from methylation data revealed an unbalanced genome, with numerous chromosomal gains and losses (Figure 2F), including gains of chromosomes 7 and 18, and losses of chromosomes 2, 3, 5, 6, 9, 16, and 20.&lt;/p&gt;&lt;p&gt;Pineoblastoma, CNS WHO grade 4; DNA methylation profile matching miRNA pathway altered, group 1A methylation class.&lt;/p&gt;&lt;p&gt;This case is an unusual example of a pineoblastoma (PB) arising in an adult. For this age group and location, pineal parenchymal tumors of intermediate differentiation (PPTIDs) and pineocytomas are much more common, but in contrast to this case show an overall more uniform and well-differentiated cellular morphology [&lt;span&gt;1&lt;/span&gt;]. Atypical teratoid/rhabdoid ","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567582","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":"Somatostatin receptors in pituitary somatotroph adenomas as predictors of response to somatostatin receptor ligands: A pathologist's perspective","authors":"Laura Botelho,&nbsp;Rômulo Sperduto Dezonne,&nbsp;Luiz Eduardo Wildemberg,&nbsp;Renan Lyra Miranda,&nbsp;Mônica R. Gadelha,&nbsp;Felipe Andreiuolo","doi":"10.1111/bpa.13313","DOIUrl":"10.1111/bpa.13313","url":null,"abstract":"<p>There are five subtypes of somatostatin receptors (SST1-5), which are expressed in several types of solid neoplasms, neuroendocrine tumors, and pituitary adenomas. Most commonly, SST2 and SST5, are of interest regarding diagnostic, treatment, and prognostic purposes. In this article the basic biological characteristics of SST are briefly reviewed, and focus given to the immunohistochemical evaluation of SST2 and SST5 in growth hormone (GH)-secreting pituitary tumors, and their quantification as predictors of response to treatment with somatostatin receptor ligands (SRL), the mainstay of the pharmacological therapy available for these tumors. Although many different scoring systems for SST2 immunohistochemistry showing correlation with SRL response have been reported, among which the immunoreactivity score (IRS) has been the most consistently used, a universally validated immunohistochemical technique and scoring scheme is lacking. Efforts should be made on collaborative multicenter studies aiming at validating homogeneous immunostaining protocols and a scoring system for SST2 and SST5 expression, to help clinicians to define the optimal therapeutic strategy for the patients with somatotroph tumors.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543849","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}