Common Central Nervous System Tumors Research Articles

Pediatric-type low-grade gliomas in adolescents and young adults-challenges and emerging paradigms.

Pediatric-type low-grade glioma (PLGG) encompasses a heterogeneous group of WHO grade 1 or 2 tumors and is the most common central nervous system tumor found in children. PLGG extends beyond pediatrics, into adolescents and young adults (AYA, ages 15-40). PLGG represents 25% of all gliomas diagnosed in AYA with differences in tumor location and molecular alterations compared to children, resulting in improved outcome for AYAs. Long-term outcome is excellent, though patients may suffer significant morbidity depending on tumor location. There are differences in treatment practices with radiation used to treat PLGG in AYAs more often than in children. Most PLGG in AYA harbor an alteration in the RAS/MAPK pathway, with limited insight into response to targeted therapy in this age group. This review discusses the epidemiology, current therapeutic approaches, and challenges in the management of PLGG in AYA.

Glioblastoma: a comprehensive approach combining bibliometric analysis, Latent Dirichlet Allocation, and HJ-Biplot : Glioblastoma insights and trends: a 49-year bibliometric analysis.

Glioblastoma is a common and aggressive malignant central nervous system tumor in adults. This study aims to evaluate and analyze the scientific results, collaboration countries, main research topics, and topics over time reported about glioblastoma. A bibliometric analysis of glioblastoma publications was performed mainly using R and Multbiplot software for author, journal, and resume. Associated statistic methods Latent Dirichlet Allocation (LDA) and HJ-Biplot. Inclusion criteria were research articles from the PubMed database published in English between 1973 and December 2022. A total of 64,823 documents with an annual growth rate of 8.27% indicates a consistent increase in research output over time. The results for the number of citations and significant publications showed Cancer Res, J Neuro-Oncol, and Neuro-Oncology are the most influential journals in the field of glioblastoma. The countries that concentrated research were the tumor United States, China, Germany, and Italy. Finally, there has been a marked growth in studies on prognosis and patient survival, therapies, and treatments for glioblastoma. These findings reinforce the need for increased global resources to address glioblastoma, particularly in underdeveloped countries. Glioblastoma research's exponential growth reflects sustained interest in early diagnosis and patient survival.

COL8A1 is a potential prognostic biomarker associated with migration, proliferation, and tumor microenvironment in glioma

Glioblastoma (GBM) is a common primary central nervous system tumor. The molecular mechanisms of glioma are unknown, and the prognosis is poor. Therefore, exploring the underlying mechanisms and screening for new prognostic markers and therapeutic targets is crucial. We utilized the weighted gene co-expression network analysis (WGCNA), Differentially Expressed Genes (DEGs), and LASSO-COX analysis to identify three target genes. Next, we constructed and evaluated a prognostic model, screening out COL8A1 as a risk gene. Through a sequence of cellular functional experiments, in vivo studies, and RNA sequencing, we delved into exploring the functional effects and molecular mechanisms of COL8A1 on GBM cells. Finally, the correlation between COL8A1 and tumor immune cells and different inflammatory responses was analyzed. Immunohistochemistry experiments revealed the influence of COL8A1 on macrophage polarization. The COL8A1 expression level was associated with the grade, prognosis, and tumor microenvironment (TME) of glioma. Functional experiments showed that COL8A1 inhibited GBM cell apoptosis and promoted migration, invasion, and proliferation in vitro and in vivo. We also found that COL8A1 promotes the epithelial-mesenchymal transition process and may mediate the activation of the ERK pathway through SHC1. In addition, immune infiltration analysis showed that COL8A1 was closely associated with macrophages in glioma tissues, significantly suppressing the signaling of M1-like -type macrophages and enhancing the signaling of M2-like -type macrophages. COL8A1 was first found to be associated with prognosis, progression, and immune microenvironment of glioma and may serve as a new marker of prognosis and a therapeutic target.

Abstract LB200: Defining the mechanisms of cancer specific transcription factor, tGLI1

Abstract Glioblastoma (GBM) is the most common malignant central nervous system tumor in adults with a five-year survival rate of less than 7%. First identified in GBM, truncated GLI1 (tGLI1), an alternative splicing isoform of GLI1, has emerged as a cancer specific GLI1 variant as tGLI1 is highly expressed in both GBM cell lines and primary specimens but not in normal tissue. Despite an in-frame loss of 41 amino acids, the tGLI1 protein has retained all known GLI1 functional domains and appears to respond to sonic hedgehog in a similar manner as GLI1. However, tGLI1 operates as a gain of function transcription factor with the ability to bind to and activate genes unique from GLI1 to promote invasion, migration, angiogenesis, and stemness in both GBM and breast cancer. Despite the advancements in our understanding of tGLI1, a genome wide DNA binding pattern of tGLI1 has not been established and the mechanism by which tGLI1 gains access to these genes is unknown. To establish a more robust understanding of the differential DNA binding patterns of GLI1 and tGLI1, we carried out ChIP-sequencing (ChIP-seq) and found only 14% of GLI1 and tGLI1 binding sites are shared. These results suggest GLI1 and tGLI1 have even more unique binding pattens across the entire genome that previously thought. However, the underlying mechanism for why GLI1 and tGLI1 bind different regions of the genome remains elusive. To determine whether variations in protein interactions of GLI1 and tGLI1 contribute to the unique binding pattern of tGLI1, we carried out immunoprecipitation (IP) followed by mass spectrometry (mass spec). Results identified 45 GLI1 associated proteins and 52 tGLI1 associated proteins with only a 29% overlap between the two. Furthermore, gene ontology analysis revealed 43% of the tGLI1-specific associated proteins are involved in processes related to RNA binding, processing, and metabolism. From these RNA-related proteins, we validated an interaction between tGLI1 and the protein NONO. NONO, which can bind both RNA and DNA, is involved in a range of molecular processes including paraspeckle formation and transcriptional regulation. In GBM, high NONO expression correlated with poor patient outcomes and the mesenchymal subtype. Interestingly, we observed that NONO, along with another essential paraspeckle component, SFPQ, had a greater interaction with tGLI1 compared to GLI1. Furthermore, co-expressing NONO with tGLI1 significantly increased clonogenic growth as well as CD44 gene transactivation using a luciferase reporter, suggesting it may play a role in tGLI1-driven stem-like properties. Furthermore, co-expression of NONO and tGLI1 increased the nuclear localization of both proteins. Together, these results show NONO may enhance tGLI1 nuclear localization, transcriptional activity, and exacerbate tGLI1-driven phenotypes. These effects of NONO could also contribute to the differential binding pattern between GLI1 and tGLI1. Citation Format: Haddie DeHart, Nolan Gregg, Richard Carpenter. Defining the mechanisms of cancer specific transcription factor, tGLI1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB200.

Molecular characterization and survival analysis of a cohort of glioblastoma, IDH-wildtype

Glioblastoma, IDH-wild type, the most common malignant primary central nervous system tumor, represents a formidable challenge in clinical management due to its poor prognosis and limited therapeutic responses. With an evolving understanding of its underlying biology, there is an urgent need to identify prognostic molecular groups that can be subject to targeted therapy. This study established a cohort of 124 sequential glioblastomas from a tertiary hospital and aimed to find correlations between molecular features and survival outcomes. Comprehensive molecular characterization of the cohort revealed prevalent alterations as previously described, such as TERT promoter mutations and involvement of the PI3K-Akt-mTOR, CK4/6-CDKN2A/B-RB1, and p14ARF-MDM2-MDM4-p53 pathways. MGMT promoter methylation is a significant predictor of improved overall survival, aligned with previous data. Conversely, age showed a marginal association with higher mortality. Multivariate analysis to account for the effect of MGMT promoter methylation and age showed that, in contrast to other published series, this cohort demonstrated improved survival for tumors harboring PTEN mutations, and that there was no observed difference for most other molecular alterations, including EGFR amplification, RB1 loss, or the coexistence of EGFR amplification and deletion/exon skipping (EGFRvIII). Despite limitations in sample size, this study contributes data to the molecular landscape of glioblastomas, prompting further investigations to examine these findings more closely in larger cohorts.

341 Racial Disparities in Incidence, Treatment, and Survival in Adult Brain Metastases: A 10-Year National Database Analysis

INTRODUCTION: Brain metastases are the most common central nervous system tumors in the United States. It is imperative to understand how prognosis and survival varies demographically to ensure equitable care for vulnerable populations and reduce financial burdens on the healthcare system. METHODS: Using the Surveillance, Epidemiology, and End Result Program (SEER) database, adults with non-primary brain metastases between 2010 and 2019 were identified. The primary outcome measure was all-cause mortality within 5 years. Chi-squared tests of independence and one way analyses of variance were used to compare group differences between White, Black, Asian/Pacific Islander (A/PI), and American Indian/Alaskan Native patients. A Cox proportional hazards model was developed to evaluate the risk of death within 5 years. RESULTS: A total of 65,154 patient records were identified following exclusion based on age (>84 years or <18 years), missing race data, and missing survival data. The incidence of brain metastases increased from 2.53 per 100,000 adults in 2010 to 2.71 per 100,000 in 2019. A/PI patients had the highest population-adjusted incidence, highest population proportion of high income, the longest time from diagnosis to treatment, lowest rate of radiation refusal, and highest rate of chemotherapy treatment. Subsequently, A/PI patients had the highest 5-year survival rate compared to White and Black patients (9.05% vs. 4.15% vs. 3.23% respectively, p < 0.001). Chemotherapy (OR = 0.44) and surgery (OR = 0.51) were the strongest protective factors against death while being widowed (OR = 1.15) and having primary lung cancer (OR = 1.14) strongest risk factors. CONCLUSIONS: A/PI patients also have a significant survival advantage compared to White, Black, and AI/AN patients, potentially due to higher rates of radiation and chemotherapy treatment. Patients of other races are recommended treatment at lower rates than A/PI patients, suggesting a discrepancy in services offered to these patients.

204 Laster Interstitial Thermal Therapy for Primary and Recurrent Meningioma: A Prospective and Retrospective Multi-institutional Study

INTRODUCTION: Meningiomas are a common central nervous system tumor, and a subset are aggressive lesions resistant to standard therapies. Laser interstitial thermal therapy (LITT) has been successfully applied to other brain tumors, but its role in meningioma treatment is understudied. METHODS: Eight United States-based hospitals enrolled patients with meningioma in the prospective multicenter registry and pooled additional retrospective enrollments for this cohort study. Demographics, procedural, safety, and outcomes data were collected and analyzed using standard statistical methods. RESULTS: Twenty adult patients (12 prospective, 8 retrospective) with LITT-targeted meningiomas were accrued. Patients underwent LITT for primary (6 patients) and recurrent tumors (14 patients, ranging from 1st to 12th recurrence). Twenty percent of patients (4/20) had exhausted all other treatment options. Median length of follow-up was 1.3 years. One-third of primary (2/6) and one-half of recurrent meningiomas (7/14) recurred during follow-up. Of those with grading information, grade 2 meningiomas were most common (9/18), followed by Grade 1(5/18), and Grade 3 (4/18). Sixty percent (60%) of patients (12/20) had convexity meningiomas treated with LITT. 2 patients (10%) had post-procedural complications, of which one resolved. One-year estimated local control (LC), progression-free survival, and overall survival were 55.3%, 48.4%, and 86.3%, respectively. In the 10 patients who had 91% ablative coverage, 1-year estimated LC was 64.8%. High grade (Grades 2 and 3) patients (n = 13) treated with LITT had a 1-year LC of 46.3%. CONCLUSIONS: This cohort represents the largest series of patients with meningioma undergoing LITT and supports the safety of the procedure in this tumor type. LITT can offer a much-needed treatment option, especially for those with multiply recurrent meningiomas and where heavy pretreatment limits remaining treatment options. LITT should be considered in the armamentarium of treatment options for meningiomas.

1235 Using Supervised Machine Learning to Validate a Novel Scoring System for the Prediction of Disease Remission of Functional Adenomas Following Transsphenoidal Resection

INTRODUCTION: Functional pituitary adenomas are common primary central nervous system tumors with potent systemic endocrinological effects. Postoperatively, remission rates range from 65-98%. METHODS: 392 adult patients who underwent primary resection of a functional pituitary adenoma at the three Mayo Clinic between 2006-2022 were retrospectively reviewed. Multivariate logistic regression was performed to identify variables predictive of disease remission. Variables found statistically significant on multivariate analysis were incorporated into our proposed pituitary-SCHEME score. Machine learning models were implemented to compare the accuracy of the pituitary-SCHEME score against the multivariate models. After training (314 patients) and cross-validation of the machine learning models, an independent testing set of 78 patients was performed. SPSS V27 and R4.2.1 were used for statistical analyses. RESULTS: 261 (66.6%) patients achieved post-operative biochemical remission. On multivariate analysis gross-total resection and Knosp-Grade 0,I,II adenomas were predictive of disease remission following resection, while macroadenomas (adenoma > 10mm), male sex, mammosomatotroph and Mixed Growth-Hormone + Prolactin adenomas were predictive of continued disease. In machine learning models, without Pituitary-SCHEME score, the K-Nearest Neighbors (KNN) model achieved the highest accuracy at 75.6% followed by Naive Bayes model. An increase in model sensitivity was achieved with inclusion of Pituitary-SCHEME score with the Linear-Discriminant-Analysis (LDA) model achieving the highest accuracy at 86.9%, followed by the Classification and Regression Trees (CART) model. The random forest model had the largest AUC-ROC among models with and without pituitary-SCHEME score. Model prediction accuracy (with vs. without pituitary-SCHEME score) were found to be statistically different based on Wilcoxon rank sum testing (p < 0.0001). CONCLUSIONS: The novel pituitary-SCHEME score, which incorporates perioperative and endocrinological measures, has promise as a clinical tool to predict patient outcomes following surgical resection of functional adenomas.

Dexamethasone in Patients with Glioblastoma: A Systematic Review and Meta-Analysis.

Glioblastomas are the most common primary central nervous system (CNS) tumors. Although modern management strategies have modestly improved overall survival, the prognosis remains dismal, with treatment side effects often impinging on the clinical course. Glioblastomas cause neurological dysfunction by infiltrating CNS tissue and via perifocal oedema formation. The administration of steroids such as dexamethasone is thought to alleviate symptoms by reducing oedema. However, despite its widespread use, the evidence for the administration of dexamethasone is limited and conflicting. Therefore, we aimed to review the current evidence concerning the use and outcomes of dexamethasone in patients with glioblastoma. We performed a systematic review and meta-analysis according to the PRISMA-P guidelines. We performed a restricted search using the keywords "Dexamethasone" and "Glioblastoma" on PubMed, Web of Science, Cochrane Library, and Academic Search Premier. We included studies reporting on overall survival (OS) and progression-free survival (PFS) in glioblastoma patients receiving higher or lower dexamethasone doses. The risk of bias was assessed using ROBINS-I. We performed a meta-analysis using a random effects model for OS and PFS. Twenty-two retrospective studies were included. Higher doses of dexamethasone were associated with poorer OS (hazard ratio 1.62, confidence interval 1.40-1.88) and PFS (1.49, 1.23-1.81). OS remained worse even when studies corrected for clinical status (1.52, 1.38-1.67). Despite the widespread use of dexamethasone in glioblastoma patients, its use is correlated with worse long-term outcomes. Consequently, Dexamethasone administration should be restricted to selected symptomatic patients. Future prospective studies are crucial to confirm these findings.

302 Targeted Inhibition of the Epigenetically Activated miR-483-5p IGF-2 Pathway as a Novel Therapeutic Strategy for Meningioma

INTRODUCTION: Meningioma is the most common primary central nervous system tumor. These are usually treated by surgical resection with curative intent, however gross total resection is not always feasible and there are many cases of recurrent and refractory disease despite adjuvant radiotherapy. Presently, there is no effective pharmacotherapeutic options for these tumors. METHODS: Small RNA sequencing was performed on meningioma tumor samples to study grade-dependent changes in microRNA expression. Gene expression was analyzed by chromatin marks, qRT-PCR and western blot. miRNA modulation, anti-IGF-2 neutralizing antibodies, and inhibitors against IGF1R were evaluated in a tumor-derived primary cultures of meningioma cells. RESULTS: Meningioma tumor samples showed high, grade-dependent expression of miR-483-5p, associated with high mRNA and protein expression of its host gene IGF-2. Inhibition of miR-483-5p reduced the growth of cultured meningioma cells, whereas a miR-483 mimic increased cell proliferation. Similarly, inhibition of this pathway with anti-IGF-2 neutralizing antibodies reduced meningioma cell proliferation. Small molecule tyrosine kinase inhibitor blockade of the IGF-2 receptor (IGF1R) resulted in rapid loss of viability of cultured meningioma tumor-derived cells, suggesting that autocrine IGF-2 feedback is obligatory for meningioma tumor cell survival and growth. The observed IGF1R-inhibitory IC50 for GSK1838705A and Ceritinib in cell-based assays along with the available pharmacokinetics data predicted that effective drug concentration could be achieved in vivo as a new medical treatment of meningioma. CONCLUSIONS: Meningioma cell growth is critically dependent on autocrine miR-483/IGF-2 stimulation and the IGF-2 pathway provides a new feasible meningioma treatment target.

Abstract 1174: Incorporation of multisector analysis into the design of personalized DNA vaccines for patients with newly diagnosed glioblastoma

Abstract Glioblastoma (GBM) is the most common malignant central nervous system (CNS) tumor in adults. Despite multimodality treatment including surgery, radiation, and chemotherapy, patients with GBM have a median survival of less than 2 years. Recent clinical trials have reported promising results using cancer vaccines to stimulate a tumor-directed immune response in several histologies. The majority of trials targeted tumor neoantigens derived from a single tumor sample, which limits the antigen pool in spatially heterogeneous cancers like GBM. Our group previously implemented multisector sequencing into the design of personalized peptide vaccines to increase the candidate pool of targetable neoantigens (NCT03422094). Although the peptide vaccine treatment was successful in stimulating an effector T cell response, it was limited by a long turnaround time from vaccine design to administration and a low peptide production rate. Therefore, we incorporated multisector sampling into the design of a personalized DNA-based GBM vaccine (NCT04015700). An average of 33% of the candidate targetable neoantigens were spatially restricted to a single sampled region, which would have been missed without multisector sequencing. DNA-based vaccines are potentially advantageous over peptide-based vaccines because they enable a higher neoantigen payload and faster manufacturing time with potent immunogenicity. Here, we report the results from 9 subjects enrolled onto the study. Spatially distinct tumor regions were subjected to whole exome sequencing (WES) and RNA-sequencing (RNA-seq), data from which were used to identify neoantigens through the pVACseq algorithm (http://pvactools.org). An average of 32 neoantigens were included in each DNA vaccine, compared to an average of only 9 for the peptide vaccine, and the turnaround time from date of surgery to administration of the DNA vaccine was about half the time. Three subjects had radiographic evidence of tumor progression prior to vaccination, highlighting the aggressive nature of GBM and the need for short manufacturing timeframes. PBMCs pre- and post-DNA vaccination were collected from 7/9 subjects. All subjects presented detectable responses and 6/7 tested revealed a sustained increment in T cell reactivity against tumor neoantigens post-treatment by IFN-γ ELISpot. Intracellular staining showed a neoantigen-specific antitumor CD8/CD4 T cell cytolytic (CD69+, CD107a+) and proliferative (Ki67+) profile. Post-vaccination tumor resections were performed for 2 subjects who also were treated with PD1 blockade upon progression, providing an opportunity to explore vaccine-induced changes in the tumor microenvironment. Herein, we demonstrate the advantages of incorporating multisector sequencing into the development of DNA-based GBM vaccines and provide insights into the resulting immune responses. Citation Format: Elizabeth A. Garfinkle, Katherine E. Miller, Alexandra J. Livingstone, Renzo Perales-Linares, Neil Cooch, Alfredo Perales-Puchalt, Sarah Rochestie, Joann Peters, Niranjan Y. Sardesai, William E. Gillanders, Elaine R. Mardis, Gavin P. Dunn, Tanner M. Johanns. Incorporation of multisector analysis into the design of personalized DNA vaccines for patients with newly diagnosed glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1174.

Retrospective study of CNS tumors in a tertiary care centre in Western Odisha - A 4 year study

Central nervous system (CNS) tumors comprise nearly 3% of all malignancies world-wide whereas in India it accounts for about 2%. In recent years there has been an increase in CNS tumors with new potential risk factors being observed. The aim of the present study is to highlight the histopathological spectrum of brain tumors in a single tertiary care centre in Western Odisha.This retrospective histopathological analysis of CNS tumors was conducted in the Department of Pathology, VIMSAR, Burla, Odisha, India from October 2016 to September 2020. In the span of 4 years, a total of 94 neurosurgical biopsies were studied. Histopathological examination of routinely processed tissue and hematoxylin and eosin (H&E) stained sections of corresponding cases were thoroughly examined. Immunohistochemistry (IHC) was done whenever required. Thereafter an approach was made to diagnose the cases, based on WHO classification system of 2016.A wide range of histopathological spectrum of CNS tumors was observed and was classified according to the WHO classification system of 2016. The primary CNS tumors were graded from Grade I to Grade IV. The most common CNS tumor in our study we found to be Astrocytic tumors (21 cases, 22.34%) followed by Schwannoma (19 cases, 20.21%) and meningiomas (18 cases, 19.14%). The incidence was more among males (59.51%) as compared to females (40.4%). This study provides an information regarding the prevalence of disease in Western Odisha. Use of modern imaging technique helps to a major extent in making a provisional.

Liquid Biopsy for Glioma Using Cell-Free DNA in Cerebrospinal Fluid.

Glioma is one of the most common primary central nervous system (CNS) tumors, and its molecular diagnosis is crucial. However, surgical resection or biopsy is risky when the tumor is located deep in the brain or brainstem. In such cases, a minimally invasive approach to liquid biopsy is beneficial. Cell-free DNA (cfDNA), which directly reflects tumor-specific genetic changes, has attracted attention as a target for liquid biopsy, and blood-based cfDNA monitoring has been demonstrated for other extra-cranial cancers. However, it is still challenging to fully detect CNS tumors derived from cfDNA in the blood, including gliomas, because of the unique structure of the blood-brain barrier. Alternatively, cerebrospinal fluid (CSF) is an ideal source of cfDNA and is expected to contribute significantly to the liquid biopsy of gliomas. Several successful studies have been conducted to detect tumor-specific genetic alterations in cfDNA from CSF using digital PCR and/or next-generation sequencing. This review summarizes the current status of CSF-based cfDNA-targeted liquid biopsy for gliomas. It highlights how the approaches differ from liquid biopsies of other extra-cranial cancers and discusses the current issues and prospects.

Pediatric spinal ependymoma with chromothripsis of chromosome 6: a case report and review of the literature

BackgroundEpendymomas are the third most common central nervous system tumor in the pediatric population; however, spinal ependymomas in children are rare. Ependymomas affecting the spinal cord most frequently occur in adults of 20–40 years of age. The current World Health Organization classification system for ependymomas is now composed of ten different entities based on histopathology, location, and molecular studies, with evidence that the new classification system more accurately predicts clinical outcomes.Case presentationWe present the case of a 16-year-old Caucasian female patient with a history of type 2 neurofibromatosis with multiple schwannomas, meningioma, and spinal ependymoma. Chromosome analysis of the harvested spinal ependymoma tumor sample revealed a 46,XX,−6,+7,−22,+mar[16]/46,XX[4] karyotype. Subsequent OncoScan microarray analysis of the formalin-fixed paraffin-embedded tumor sample confirmed + 7, −22 and clarified that the marker chromosome represents chromothripsis of the entire chromosome 6 with more than 100 breakpoints. Fluorescent in situ hybridization and microarray analysis showed no evidence of MYCN amplification. The final integrated pathology diagnosis was spinal ependymoma (central nervous system World Health Organization grade 2 with no MYCN amplification.ConclusionThis case adds to the existing literature of pediatric patients with spinal ependymomas and expands the cytogenetic findings that may be seen in patients with this tumor type. This case also highlights the value of cytogenetics and microarray analysis in solid tumors to provide a more accurate molecular diagnosis.

Terson’s Syndrome due to Ependymoma: A Rare Case Report

Abstract
 Introduction : Terson's syndrome is often associated with subarachnoid hemorrhage. Other reported causes, include trauma, tumors, hypertension, perioperative and postoperative intracranial hemorrhage, or increased intracranial pressure. This case demonstrates a unique pathogenesis of Terson's syndrome.
 Case Illustration : A 14-year-old boy presented with the blurred vision on both eyes 3 weeks ago, accompanied with nausea, vomiting, and headache, with normal blood pressure measurement (126/80mmHg). He also had a history of head injury. His visual acuity was 6/20 uncorrected with pinhole on both eyes. Both intraocular pressures within normal limits. The anterior segment showed bilateral mid-dilated reactive pupil. Funduscopy revealed bilateral papilledema with peripapillary hemorrhage, similar to retinal vein occlusion, which is suggestive with Terson’s Syndrome. Magnetic Resonance Imaging (MRI) scan showed an ependymoma mass. We consulted this case with Pediatric Neurosurgeon, who planned for ventriculoperitoneal shunt with craniotomy tumor removal.
 Discussion : Terson's syndrome now defined as any intraocular hemorrhage associated with intracranial hemorrhage or elevated intracranial pressures. In this case, the etiology was thought to be increased intracranial pressure, which may be caused by ependymoma. Ependymoma is one of the most common central nervous system tumors in children. Intraocular hemorrhage in Terson’s syndrome is often self-limiting, but ependymoma needs neurosurgical intervention, which has lower survival rates for children with posterior fossa tumors.
 Conclusion : There are still controversies regarding the pathogenesis of Terson's syndrome. Not the occlusion, but the compression of the central retinal vein, by the increased pressure of cerebrospinal fluid due to high intracranial pressure, which increases the retinal venous pressure and causes retinal hemorrhage.

Etomidate inhibits tumor growth of glioblastoma by regulating M1 macrophage polarization.

Glioblastoma (GBM) is a common primary central nervous system tumor. Although the multimodal integrated treatment for GBM has made great progress in recent years, the overall survival time of GBM is still short. Thus, novel treatments for GBM are worth further investigation and exploration. This study aimed to investigate the effects of etomidate on GBM tumor growth and the underlying mechanism. A xenograft tumor model was established and treated with etomidate to assess tumor growth. Immunohistochemistry (IHC) assay evaluated the positive rate of Ki67 cells in tumor tissues. Cell counting kit (CCK)-8 and EdU assays accessed the cell viability and proliferation. Immunofluorescence (IF) staining detected the distribution of macrophage markers in tumor tissues. The percentages of M1- and M2-like macrophages in tumor-associated macrophages (TAMs) and co-culture system (macrophages and GBM cells) were detected using flow cytometry. Macrophage polarization-related genes were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Etomidate treatment inhibited the tumor growth, and increased the CD86+ cells but decreased the CD206+ cells in TAMs. The gene expression of M1 markers was increased in TAMs of etomidate-treated mice, whereas that of M2 markers was decreased. Moreover, etomidate treatment increased the number of CD86+ M1-like macrophages co-cultured with tumor cells but decreased that of CD206+ M2-like macrophages, with the upregulation of M1 markers and downregulation of M2 markers. Etomidate inhibited GBM tumor growth by promoting M1 macrophage polarization, suggesting a new insight into the clinical treatment of GBM.

Liquid biopsy evaluation of circulating tumor DNA, miRNAs, and cytokines in meningioma patients.

Liquid biopsy is a non-invasive method used to detect cancer and monitor treatment responses by analyzing blood or other bodily fluids for cancer biomarkers. Meningiomas are the most common primary central nervous system tumors, and biomarkers play a crucial role in their diagnosis, prognosis, and treatment monitoring. The World Health Organization (WHO) classifies meningiomas based on tumor grades and molecular alterations in genes such as in NF2, AKT1, TRAF7, SMO, PIK3CA, KLF4, SMARCE1, BAP1, H3K27me3, TERT promoter, and CDKN2A/B. Liquid biopsy, specifically cell-free DNA (cfDNA) analysis, has shown potential for monitoring meningiomas as it can detect ctDNA release in the blood, unaffected by the blood-brain barrier. MicroRNAs (miRNAs) have also been found to be deregulated in various cancers, including meningiomas, presenting potential as diagnostic biomarkers. Additionally, studying cytokines in the tumor microenvironment may aid in establishing prognostic or diagnostic panels for meningiomas. In the present study we analyzed the DNA coming from both the plasma and tumor samples, in addition to analyze miRNA-21 and cytokines in the plasma of 28 meningioma patients. Our findings indicate that the detection of ctDNA in the plasma of meningioma patients is feasible. However, it's important to note that certain challenges persist when comparing plasma DNA analysis to that of tumor tissues. In our study, we observed a paired identification of mutations in only one patient, highlighting the complexities involved. Furthermore, we successfully identified miR-21 and cytokines in the plasma samples. Notably, our analysis of Interleukin 6 (IL-6) unveiled higher expression in the clear cell subtype compared to the other types. Despite the ongoing research, the clinical implementation of liquid biopsy in meningiomas remains somewhat limited. Nevertheless, our promising results underscore the need for further investigation.

Intraoperative Touch Imprint Cytology of Brain Neoplasms: A Useful High-Diagnostic Tool in 93 Consecutive Cases; Differential Diagnoses, Pitfalls, and Traps.

Intraoperative cytological examination of central nervous system (CNS) lesions was first introduced in 1920 by Eisenhardt and Cushing for rapid evaluation of neurosurgical specimens and to guide surgical treatment. It is recognized that this method not only confirms the adequacy of biopsy in CNS samples but also indicates the presence and preliminary diagnosis of lesional tissue. A total of 93 patients who underwent touch imprint cytology (TIC) for CNS tumors or lesions between 2018 and 2023 were included in the study. All cases were correlated with the final histopathological diagnosis, and pitfalls and difficulties encountered with discrepancies were noted. The most common primary CNS tumors were gliomas and meningiomas, while secondary (metastatic) tumors were predominantly lung, breast, and gastrointestinal system carcinomas. Sensitivity, specificity, positive predictive value, and negative predictive value for diagnosis with TIC were 94.1%, 100%, and 61.5%, respectively. Final histopathological diagnosis by TIC was made in 88 cases (94.6%) and the discrepancy was found in 5 cases (5.37%). Three of the five discrepancies (3.2%) were haematolymphoid malignancies (two lymphomas and one plasma cell neoplasia), one glioblastoma, and one hemangioblastoma case. TIC is a fast, safe, and inexpensive diagnostic tool used during intraoperative neuropathology consultation. Awareness of the pitfalls of using this method during intraoperative consultation will enable high-diagnostic accuracy.

Impact of molecular genetic profle of meningiomas on the clinical course and recurrence using combined modality treatment

Introduction. Meningioma is one of the most common central nervous system tumors, accounting for 39.7 % of all primary brain tumors. The tumor originates from arachnoid meningothelial cells and is characterized by a wide range of histological types classified into 15 subtypes. The histological classification of meningiomas allows us to predict meningioma behavior and the risk of disease recurrence, as well as to define treatment strategies. However, clinical outcomes in histological subgroups of patients are often inconsistent with the histological grade of malignancy. Thus, a more reliable method is needed both to determine the histological subtype of the tumor and to predict the clinical course of the disease with the potential for targeted treatment.The purpose of the study was to summarize the available data on the effect of results of the genomic and proteomic tumor analysis on carcinogenesis with the relationship between the mutational changes and noninvasive diagnosis, treatment and the course of the disease.Material and Methods. Literature search was carried out in the PubMed, Elibrary system, publications were included mainly from 2010 to 2023. with the identification of articles by the keyword “genetic analysis of meningiomas” and synonyms. 550 articles were found, of which 55 were used to write a literature review.Conclusion. The study of the molecular genetic profile of meningiomas will improve the classification and establish a correlation with MRI data, the course of the disease and prognosis.

CSF cytology of common primary CNS neoplasms categorized by CNS WHO 2021.

The detection of neoplastic cells in cerebral spinal fluid (CSF) is pivotal for the management of patients with central nervous system (CNS) tumours. This article delves into the CSF cytological characteristics of common CNS neoplasms, aligning with the 2021 World Health Organization (WHO) classification of CNS tumours. A retrospective review of CSF specimens positive for primary CNS neoplasms was performed at three tertiary medical centres. Only cases that had histopathologic confirmation and/or molecular workup were included. Common primary CNS neoplasms seen in CSF cytology specimens include medulloblastoma, (non-WNT/non-SHH as well as SHH-activated and TP53 mutant), pineoblastoma, atypical teratoid/rhabdoid tumour (AT/RT), IDH-wildtype glioblastoma, and primary diffuse large B-cell lymphoma of the CNS. Ependymomas and germinomas can also have CSF involvement but are less common. Although the typical histologic architecture of these tumours may not be preserved in the CSF, unique cytomorphologic features such as nuclear moulding, nuclear pleomorphism, rhabdoid cells, prominent nucleoli and rosette formation can still be appreciated. Adopting the updated terminology and correlating cytologic observations with molecular findings will streamline the diagnostic process, reducing the complexities and ambiguities pathologists often encounter when analysing CSF specimens for potential primary CNS neoplasms.