Non-glial Tumors Research Articles

Clinical Presentation, Treatment, and Outcomes of Pediatric Brain Tumors: A 5-Year Single-Center Experience in Istanbul

Background: Brain tumors are the most common solid tumors in childhood. With the help of increased clinical awareness, improvements in imaging methods, and the identification of molecular characteristics, advances have been made in both diagnosis and treatment. Objectives: In our study, we aimed to discuss the childhood brain tumor cases followed in our clinic, along with their clinical and epidemiological features and treatment outcomes. Methods: The study group comprised children younger than 18 years old who were followed in the Pediatric Hematology and Oncology Clinic of Istanbul Medical Faculty and diagnosed with a brain tumor over the past 5 years (2018 - 2023). Symptoms, age at diagnosis, treatment options (surgery, radiotherapy, chemotherapy), and side effects were reviewed retrospectively. Results: Thirty children were diagnosed with brain tumors. Of the patients, 14 (47%) were male and 16 (53%) were female. The mean age of the children was 8.8 ± 3.1 years, and the mean age at diagnosis was 65.6 ± 37.7 months. The most common symptom was vomiting (40%). The mean duration between the onset of symptoms and diagnosis was 3.8 months, with a median of 1 month. Of the patients, 60% were diagnosed with glial tumors and 40% with non-glial tumors. Gross total resection (GTR) was performed in 26% of patients, subtotal resection (STR) in 37%, and 37% of patients did not undergo surgery. Seventy-seven percent of the patients received chemotherapy, and 57% received radiotherapy. Of the patients, 57% were considered responsive to treatment (complete/partial), 30% had stable disease, and 13% had progressive disease. The overall brain tumor mortality rate in our clinic was 13%. While 73% of our 26 patients had no or mild neurological deficits, 27% had moderate to severe disabilities (gait impairment, hearing impairment, visual impairment). Conclusion: Although the sample size was limited, it may be speculated that the surgery rate was low and long-term side effects were notable. Insufficient surgical resection can affect the treatment response and increase the risk of neurological sequelae and functional impairment. Molecular profiling should be expanded, and a palliative care team should be involved as early as possible to address long-term side effects and improve the quality of life for patients.

Metabolomic profile of cerebrospinal fluid from patients with diffuse gliomas.

Diffuse gliomas are among the most common brain tumors in adults and are associated with a dismal prognosis, especially in patients with glioblastoma. To date, tumor tissue acquisition is mandatory for conclusive diagnosis and therapeutic decision-making. In this study, we aimed to identify possible diagnostic and prognostic biomarkers in cerebrospinal fluid (CSF) and blood. During glioma surgery at our institution, CSF and blood samples were collected from patients. Subsequently, targeted metabolomics analysis was used to detect and quantify circulating metabolites. The metabolome profiles of glioma patients were compared with those of patients in a control group who had undergone neurosurgery for other entities, such as nonglial tumors or hydrocephalus, and were correlated with established glioma diagnostic molecular markers. In this study, a total of 30 glioma patients were included, along with a control group of 21 patients without glioma. Serum metabolomic analysis did not detect any significant differences between the groups, whereas CSF-metabolome analysis revealed increased levels of six metabolites in glioma patients. Among these, the most pronounced differences were found for the biogenic amine putrescine (p = 0.00005). p-Cresol sulfate was identified as a potential CSF marker for determining isocitrate dehydrogenase (IDH) status in glioma patients (p = 0.0037). CSF-metabolome profiling, unlike blood profiling, shows promise as a diagnostic tool for glioma patients with the potential to assign molecular subtypes. The next step will involve a larger multicenter study to validate these findings, with the ultimate objective of integrating CSF metabolomics analysis into clinical practice.

Towards machine learning-based quantitative hyperspectral image guidance for brain tumor resection

BackgroundComplete resection of malignant gliomas is hampered by the difficulty in distinguishing tumor cells at the infiltration zone. Fluorescence guidance with 5-ALA assists in reaching this goal. Using hyperspectral imaging, previous work characterized five fluorophores’ emission spectra in most human brain tumors.MethodsIn this paper, the effectiveness of these five spectra was explored for different tumor and tissue classification tasks in 184 patients (891 hyperspectral measurements) harboring low- (n = 30) and high-grade gliomas (n = 115), non-glial primary brain tumors (n = 19), radiation necrosis (n = 2), miscellaneous (n = 10) and metastases (n = 8). Four machine-learning models were trained to classify tumor type, grade, glioma margins, and IDH mutation.ResultsUsing random forests and multilayer perceptrons, the classifiers achieve average test accuracies of 84–87%, 96.1%, 86%, and 91% respectively. All five fluorophore abundances vary between tumor margin types and tumor grades (p < 0.01). For tissue type, at least four of the five fluorophore abundances are significantly different (p < 0.01) between all classes.ConclusionsThese results demonstrate the fluorophores’ differing abundances in different tissue classes and the value of the five fluorophores as potential optical biomarkers, opening new opportunities for intraoperative classification systems in fluorescence-guided neurosurgery.

Related mechanisms, current treatments, and new perspectives in meningioma.

Meningiomas are non-glial tumors that are the most common primary brain tumors in adults. Although meningioma can possibly be cured with surgical excision, variations in atypical/anaplastic meningioma have a high recurrence rate and a poor prognosis. As a result, it is critical to develop novel therapeutic options for high-grade meningiomas. This review highlights the current histology of meningiomas, prevalent genetic and molecular changes, and the most extensively researched signaling pathways and therapies in meningiomas. It also reviews current clinical studies and novel meningioma treatments, including immunotherapy, microRNAs, cancer stem cell methods, and targeted interventions within the glycolysis pathway. Through the examination of the complex landscape of meningioma biology and the highlighting of promising therapeutic pathways, this review opens the way for future research efforts aimed at improving patient outcomes in this prevalent intracranial tumor entity.

Anaplastic Lymphoma Kinase (ALK) in Posterior Cranial Fossa Tumors: A Scoping Review of Diagnostic, Prognostic, and Therapeutic Perspectives

Anaplastic Lymphoma Kinase (ALK) has been implicated in several human cancers. This review aims at mapping the available literature on the involvement of ALK in non-glial tumors localized in the posterior cranial fossa and at identifying diagnostic, prognostic, and therapeutic considerations. Following the PRISMA-ScR guidelines, studies were included if they investigated ALK’s role in primary CNS, non-glial tumors located in the posterior cranial fossa. A total of 210 manuscripts were selected for full-text review and 16 finally met the inclusion criteria. The review included 55 cases of primary, intracranial neoplasms with ALK genetic alterations and/or protein expression, located in the posterior fossa, comprising of medulloblastoma, anaplastic large-cell lymphoma, histiocytosis, inflammatory myofibroblastic tumors, and intracranial myxoid mesenchymal tumors. ALK pathology was investigated via immunohistochemistry or genetic analysis. Several studies provided evidence for potential diagnostic and prognostic value for ALK assessment as well as therapeutic efficacy in its targeting. The available findings on ALK in posterior fossa tumors are limited. Nevertheless, previous findings suggest that ALK assessment is of diagnostic and prognostic value in medulloblastoma (WNT-activated). Interestingly, a substantial proportion of ALK-positive/altered CNS histiocytoses thus far identified have been localized in the posterior fossa. The therapeutic potential of ALK inhibition in histiocytosis warrants further investigation.

INNV-24. MACHINE LEARNING-BASED SPECTROSCOPIC TISSUE DIFFERENTIATION IN FLUORESCENCE-GUIDED NEUROSURGERY

Abstract Maximal resection of malignant gliomas is hindered by difficulty in distinguishing tumor margins. Fluorescence-guided resection with 5-ALA assists in reaching this goal. Previously, we characterized five fluorophore emissions that accurately represent any spectrum measured from human brain tumor biopsies with a wide-field hyperspectral device. In this study, the effectiveness of these five spectra was explored for different tumor classification tasks in 891 hyperspectral widefield measurements of 184 patients harboring low- (n=30) and high-grade gliomas (n=115), non-glial primary brain tumors (n=19), radiation necrosis (n=2), miscellaneous (n=10) and metastases (n=8), which corresponds to up to 15000 spectra for a given test. The statistical differences in fluorophore abundances between classes were determined and visualized using dimensionality reduction techniques, including principal component analysis (PCA) and t-distributed stochastic neighbor embedding (t-SNE). Three machine-learning models were trained to classify tumor type (12 classes), grade (3 classes), and glioma margins (3 classes). Five algorithms were tested with varying hyperparameters for each classification task. We explored whether PCA projection onto five different axes than fluorophore abundances can provide more information for visualization and classification. The abundances of the five a priori fluorophore spectra matched or outperformed the five optimal PCA components for all classification tasks. These five axes capture 96-99% of the variance in the dataset. Using random forests and multilayer perceptrons, the classifiers achieved average test accuracies of 74-82%, 79%, and 81%, respectively. All five fluorophore abundances varied between tumor margin type as well as between grades (p &amp;lt; 0.01). For tissue type, at least four of five fluorophore abundances were found to be significantly different (p &amp;lt; 0.01) between all classes. These results demonstrate the differing contribution of fluorophores in different tissue classes tissue, as well as the five fluorophores value as potential optical biomarkers, opening new opportunities for intraoperative classification systems in fluorescence-guided neurosurgery.

Magnetic Resonance Imaging Patterns of Intracranial Meningiomas in Erbil City

Background and objectives: Meningiomas are the most common non-glial tumors of the central nervous system representing around one fifth of primary intracranial tumors with annual incidence of six per 100,000 populations. This study aimed to address the diagnostic precision of magnetic resonance imaging as a brain investigation tool to evaluate meningioma diagnosis and tumor staging before performing the operation. Methods: This study designed as a cross-sectional study and carried out between December 2019 and December 2020. A total number of 48 meningiomas resected and evaluated at three public hospitals in Erbil City. Pre-operative magnetic resonance imaging investigation and postoperative histopathological evaluation were done for all patients for their intracranial tumors and tissue sections. Results: Majority of patients showed isointense pattern on T1 (87.5%) and T2 (85.4%) signal intensity, homogenous in consistency (81.3%), the vast majority of the meningiomas were typical (93.8%) and of meningothelial type (81.3%). In most of the cases, there was no bone involvement (77.1%), no invasion of dural venous sinuses (83.3%), no calcifications (83.3%), no cystic changes (97.9%) but positive cerebral spinal fluid cleft (66.7%) and homogenous enhancement pattern (83.3%). Five out of eleven imaging patterns and configurations including T1 signal intensity, T2 signal intensity, consistency, calcification and vascularity of the meningioma were valid and reliable by calculating their sensitivity, specificity and running kappa test. Conclusions: Some magnetic resonance imaging patterns such as T1 signal intensity, T2 signal intensity, consistency, calcification, and vascularity of the meningioma are useful for predicting the stages of meningioma.

Clinical Validation of Stimulated Raman Histology for Rapid Intraoperative Diagnosis of Central Nervous System Tumors

Stimulated Raman histology (SRH) is an ex vivo optical imaging method that enables microscopic examination of fresh tissue intraoperatively. The conventional intraoperative method uses frozen section analysis, which is labor and time intensive, introduces artifacts that limit diagnostic accuracy, and consumes tissue. SRH imaging allows rapid microscopic imaging of fresh tissue, avoids tissue loss, and enables remote telepathology review. This improves access to expert neuropathology consultation in both low- and high-resource practices. We clinically validated SRH by performing a blinded, retrospective two-arm telepathology study to clinically validate SRH for telepathology at our institution. Using surgical specimens from 47 subjects, we generated a data set composed of 47 SRH images and 47 matched whole slide images (WSIs) of formalin-fixed, paraffin-embedded tissue stained with hematoxylin and eosin, with associated intraoperative clinicoradiologic information and structured diagnostic questions. We compared diagnostic concordance between WSI and SRH-rendered diagnoses. Also, we compared the 1-year median turnaround time (TAT) of intraoperative conventional neuropathology frozen sections with prospectively rendered SRH-telepathology TAT. All SRH images were of sufficient quality for diagnostic review. A review of SRH images showed high accuracy in distinguishing glial from nonglial tumors (96.5% SRH vs 98% WSIs) and predicting final diagnosis (85.9% SRH vs 93.1% WSIs). SRH-based diagnosis and WSI-permanent section diagnosis had high concordance (κ = 0.76). The median TAT for prospectively SRH-rendered diagnosis was 3.7 minutes, approximately 10-fold shorter than the median frozen section TAT (31 minutes). The SRH-imaging procedure did not affect ancillary studies. SRH generates diagnostic virtual histologic images with accuracy comparable to conventional hematoxylin and eosin-based methods in a rapid manner. Our study represents the largest and most rigorous clinical validation of SRH to date. It supports the feasibility of implementing SRH as a rapid method for intraoperative diagnosis complementary to conventional pathology laboratory methods.

Exceptionally rare IDH1-mutant adult medulloblastoma with concurrent GNAS mutation revealed by in vivo magnetic resonance spectroscopy and deep sequencing

Medulloblastoma (MB) is the most common malignant brain tumor occurring in childhood and rarely found in adults. Based on transcriptome profile, MB are currently classified into four major molecular groups reflecting a considerable biological heterogeneity: WNT-activated, SHH-activated, group 3 and group 4. Recently, DNA methylation profiling allowed the identification of additional subgroups within the four major molecular groups associated with different clinic-pathological and molecular features. Isocitrate dehydrogenase-1 and 2 (IDH1 and IDH2) mutations have been described in several tumors, including gliomas, while in MB are rarely reported and not routinely investigated. By means of magnetic resonance spectroscopy (MRS), we unequivocally assessed the presence the oncometabolite D-2-hydroxyglutarate (2HG), a marker of IDH1 and IDH2 mutations, in a case of adult MB. Immunophenotypical work-up and methylation profiling assigned the diagnosis of MB, subclass SHH-A, and molecular testing revealed the presence of the non-canonical somatic IDH1(p.R132C) mutation and an additional GNAS mutation, also rarely described in MB. To the best of our knowledge, this is the first reported case of MB simultaneously harboring both mutations. Of note, tumor exhibited a heterogeneous phenotype with a tumor component displaying glial differentiation, with robust GFAP expression, and a component with conventional MB features and selective presence of GNAS mutation, suggesting co-existence of two different major tumor subclones. These findings drew attention to the need for a deeper genetic characterization of MB, in order to get insights into their biology and improve stratification and clinical management of the patients. Moreover, our results underlined the importance of performing MRS for the identification of IDH mutations in non-glial tumors. The use of throughput molecular profiling analysis and advanced medical imaging will certainly increase the frequency with which tumor entities with rare molecular alterations will be identified. Whether these findings have any specific therapeutic implications or prognostic relevance requires further investigations.

The relationship between connexin-43 expression and Ki67 in non-glial central nervous system tumors.

Advanced intercellular communication is a known oncogenic factor. In the central nervous system, Connexin-43 (Cx43) forms this junctional networking. Moreover, it correlates with the proliferation rate, and thus behavior, of gliomas. We assessed the expression of Cx43 and its relationship to Ki67 in other common central nervous system tumors. The expression of Cx43 and Ki67 were assessed in formalin-fixed paraffin embedded samples of human brain metastases, meningiomas, and neurinomas using immunohistochemistry. Neurinomas and meningiomas were jointly evaluated due to similar non-malignant behavior. A total of 14 metastases of different extracerebral carcinomas, 6 meningiomas, and 10 neurinomas were evaluated. Five (36%) metastases and 5 (31%) meningiomas/neurinomas showed minor expression, whereas 6 (43%) metastases and 2 (13%) meningiomas/neurinomas showed no Cx43 expression at all. In 3 (21%) metastases and 9 (56%) meningiomas/neurinomas, moderate or strong expression of Cx43 was identified. The higher expression of Cx43 in meningiomas and neurinomas directly correlated with Ki67, r = 0.53 (P = 0.034). For metastases no significant correlation was found. Mitotic index in meningiomas/neurinomas correlated with Ki67 expression, r = 0.74 (P < 0.001), but did not show statistically significant correlation with Cx43 expression in these tumors. The expression of Cx43 as a marker of cell-to-cell networking exposed a significant correlation with the Ki67-defined proliferation index in case of primary central nervous system neuroectodermal neoplasms. However, it does not seem to play a comparable role in metastases with extracerebral origin.

Laser Interstitial Thermal Therapy for the Treatment of Primary and Metastatic Brain Tumors: A Systematic Review and Meta-Analysis

Laser interstitial thermal therapy (LITT) is a minimally invasive treatment option for intracranial tumors that are challenging to treat via traditional methods; however, its safety and efficacy are not yet well validated in the literature. The objectives of the study were to assess the available evidence of the indications and adverse events (AEs) of LITT and 1-year progression-free survival and 1-year overall survival in the treatment of primary and secondary brain tumors. A comprehensive literature search was conducted through the databases PubMed, Embase, and the Cochrane Library until October 2021. Comparative and descriptive studies, except for case reports, were included in the meta-analysis. Separate analyses by tumor type (high-grade gliomas, including World Health Organization grade 4 astrocytomas [which include glioblastomas] as a specific subgroup; low-grade gliomas; and brain metastases) were conducted. Pooled effect sizes and their 95% confidence intervals (CI) were generated via random-effects models. Forty-five studies met the inclusion criteria, yielding 826 patients for meta-analysis. There were 829 lesions in total, of which 361 were classified as high-grade gliomas, 116 as low-grade gliomas, 337 as metastatic brain tumors, and 15 as nonglial tumors. Indications for offering LITT included deep/inaccessible tumor (12 studies), salvage therapy after failed radiosurgery (9), failures of ≥2 treatment options (3), in pediatric patients (4), patient preference (1); indications were nonspecific in 12 studies. Pooled incidence of all (minor or major) procedure-related AEs was 30% (95% CI, 27%-40%) for all tumors. Pooled incidence of neurologic deficits (minor or major) was 16% (12%-22%); postprocedural edema 14% (8%-22%); seizure 6% (4%-9%); hematoma 20% (14%-29%); deep vein thrombosis 19% (11%-30%); hydrocephalus 8% (5%-12%); and wound infection 5% (3%-7%). One-year progression-free survival was 18.6% (11.3%-29.0%) in high-grade gliomas, 16.9% (11.6%-24.0%) among the grade 4 astrocytomas; and 51.2% (36.7%-65.5%) in brain metastases. One-year overall survival was 43.0% (36.0%-50.0%) in high-grade glioma, 45.9% (95% CI, 37.9%-54%) in grade 4 astrocytomas; 93.0% (42.3%-100%) in low-grade gliomas, and 56.3% (47.0%-65.3%) in brain metastases. New neurologic deficits and postprocedural edema were the most reported AEs after LITT, albeit mostly transient. This meta-analysis provides the best statistical estimates of progression and survival outcomes based on the available information. LITT is generally a safe procedure for selected patients, and future well-designed comparative studies on its outcomes versus the current standard of care should be performed.

CNSC-37. ATYPICAL GERMLINE MUTATIONS AND PRIMARY CNS TUMORS: A SINGLE-CENTER CASE SERIES AND LITERATURE REVIEW

Abstract A growing spectrum of germline mutations and their association with primary CNS tumors has been described over the last decade. These germline mutations are implicated in regulation of DNA integrity and repair, telomere maintenance, and cell cycle regulation resulting in aberrant cellular proliferation and immune surveillance evasion. To date, there are no well-defined guidelines for primary CNS tumor surveillance for these patients. Moreover, the exact role of traditional chemotherapy, immunotherapy, and radiation is unclear. We present a single-institution case series of adult patients with primary CNS tumors with atypical germline mutations and literature review. The most common germline mutations encountered involved heterozygous mutations of one of the mismatch repair (MMR) genes (MSH2, PMS2, MLH1). All patients developed high-grade gliomas defined as astrocytoma or glioblastoma WHO grade 4 based on the WHO 2021 classification. Germline mutations involving RAD51C, POT1, IDH1/2, MutyH, NTHL1, PALB2, and CHEK2 were associated with gliomas of variable grades and molecular subtypes. Non-glial tumors, including atypical rhabdoid tumors, medulloblastomas, hemangioblastomas, and meningiomas were found in association with germline SMARCB1, ATM, BRCA1, and CHEK2 mutations respectively. Review of the existing literature and knowledge obtained from our case series suggests several important concepts: (1) there is an increased risk of both glioma and non-glial tumor types in several atypical germline mutations, (2) multiple risk genes or variants of unknown significance likely contribute to primary brain tumor formation, (3) germline MMR mutations associated with high-grade glioma may be MMR gene-specific with potential increased risk of resistance and/or disease progression in the presence of alkylating agents such as temozolomide, (4) several germline mutations may increase risk of secondary tumor development after radiation, and (5) the role of screening for atypical germline mutations and subsequent disease surveillance remain unanswered.

STEM-12. DISCOVERY THE ORIGIN-CELLS FOR HUMAN GLIOBLASTOMA GENESIS IN SUBVENTRICULAR ZONE

Abstract Human glioblastoma (GBM), originating from the subventricular zone (SVZ), occurs due to molecular disruptions in chromosomes. Most GBM tissues exhibit definitive chromosomal patterns: copy-number-variations (CNV) in chromosome 7 (gain) and 10 (loss), known as the earliest molecular events. Herein, we hypothesised that the origin-cells in SVZ of GBM patients can provide clues regarding these chromosomal alterations. We compared bulk RNA sequencing (RNAseq) data of GBM tumor tissue (n=126), tumour free GBM SVZ (n=40), and tumor-free control SVZ of non-glial tumor (n=9). Paired single-cell-level RNAseq samples of tumor free GBM SVZ (n=7) and GBM tumor tissue (n=10), were done to see cell specific CNVs. Using human SVZ and GBM samples as a background, we generated origin-cell and origin-cell-derived tumour cell using CRISPR/Cas9. In this work, we identified two GBM-origin-cell types with stem-cell signatures during single-cell level analyses of 60 SVZ tissue samples obtained from tumor-free regions of GBM patients. Furthermore, single-cell level analysis revealed that two origin-cell types in SVZ harbor ongoing patterns of CNV alterations. Among the origin-cells found in the SVZ of GBM patients, NO-like cells showed neural progenitor plus oligodendrocyte progenitor (NO) signature, while AN-like cells showed astrocyte plus neural stem cell (AN) signature. For the interconnectedness, we subjected single-cell-level RNA-seq data to ligand-receptor connection analysis. In the stem cell mode, NO-like cells was connected to AN-like cells in SVZ samples and while in the tumor samples, cycling cell was connected to AN-like cells. NO-like cells was common in TERT promoter wildtype GBM and AN-like cells was more common in TERT promoter mutant GBM. CRISPR/Cas9 models revealed accumulation copy-number alterations from non-tumorigenic origin-cells to tumor cells. These two origin-cells (NO-like cells and AN-like cells) derived from the SVZ of the adult human brain will facilitate the understanding of GBM genesis and development of potential novel therapeutic targets.

OS10.6.A What is the initial cell in the subventricular zone for human glioblastoma genesis?

Abstract Background We all have a fundamental question about why glioblastoma (GBM) develops. In order to find the answer to this fundamental question, if you find out what the first cell is, you will get closer to the answer. GBM arises from the subventricular zone (SVZ). GBM is one of the most devastating tumour of human brain as the most optimal treatment barely prolongs the survival, and it does not cure the disease. As the majority of GBM tissues show copy number variations (CNV) of co-altered chromosomal 7 gain and 10 loss, we hypothesized the origin cell (Oc) of SVZ may be traced back with these markers. The cellular identity of the Oc is still unknown and it is different from the tumour-derived progenitor-like cells. We aimed to define these cells from the SVZ that have a potential to get activated into GBM. Material and Methods We compared bulk RNA sequencing (RNAseq) data of IDHwt GBM tumor tissue (n=122), tumor free SVZ from GBM patients (n=40), tumor-free control SVZ of non-glial tumor (n=9). Pared single nucleus RNAseq (snRNAseq) or single cell RNAseq (scRNAseq) samples of tumor free SVZ (n=11) and GBM tumor (n=8), were done to see cell specific CNVs. We developed genetically engineered mouse models for GBM genesis introducing three driver mutations (TP53, PTEN, and EGFRviii) into SVZ to isolate mouse Oc (mOc) and mouse cancer cells (mCc). The biological characteristics of separated mOc and mCc were compared. Bulk RNAseq and scRNAseq were performed on these cells (mOc, mCc), and their cellular state was compared with the human gene set. Results In this work, we found two types of the Oc in the RNA sequencing of 60 human tumour free-SVZ samples. Furthermore, single-cell level analysis revealed that two Oc types in SVZ harbor ongoing patterns of CNV co-alterations from Oc1 to Oc2, and finally to GBM. The Oc1 type cells contained the CNV signature of Oc2 ancestor with neural progenitor cell (NPC) signature. Oc2 type cells expressed a high level of EGFR than other cells with astrocyte-like cell signature. Both of these cells expressed oligodendrocyte progenitor cell (OPC)-like signatures in the SVZ. We validated the human-based findings by using the P53/PTEN/EGFR-mutant mouse model with EGFR/tdTomato overexpression and P53/PTEN knockout in the SVZ cells. As a result, non-tumourigenic and highly motile Oc-like cell-states are found in the mouse models, supporting the firework-like migration pattern from the SVZ. Conclusion Our results demonstrate how members of Oc preoccupy the SVZ, known as the stem cell niche and give rise to the tumour. We anticipate that a new therapy may emerge by targeting the Oc in the SVZ.

Hemorrhagic Meningioma With Symptom of Convulsion: A Rare Presentation of Parietal Meningioma

Meningioma is the most common, extra-axial, non-glial intracranial tumor with an incidence of 2.3- 5.5/100000, accounting for 20%-30% of all primary brain tumor diagnoses in adults. Meningiomas associated with intratumoral hemorrhage are very rare occurring in 0.5%-2.4%. of individuals. Herein, we report a rare case of hemorrhagic meningioma with the symptom of convulsion. The case was a 68-year-old woman admitted to the hospital with severe headache and convulsions. Computed tomography revealed an increase in heterogeneous lesion measuring 4×3×2.5 cm at the right parietal lobe. Brain magnetic resonance imaging (MRI) showed a grossly stable homogeneously enhancing extra-axial mass measuring 43×33×28 mm, small calcified peripheral, intratumoral hemorrhage. Histopathology showed a multi-celled meningioma with bleeding areas (WHO grade I).

β-Catenin marks proliferating endothelial cells in glioblastoma

BackgroundAngiogenesis is a key process in the growth and maintenance of tumors. The Wnt signaling pathway is required for angiogenesis of the central nervous system though development of the blood–brain barrier and subsequent proliferation of endothelial cells during tumor growth. However, the specificity of the Wnt pathway in regulating endothelial cells of different central nervous systems remains to be investigated. Materials & methodsPatient-derived tissue samples from 35 paraffin-embedded tumors were used to assess β-catenin immunoexpression. Tumor samples consisted of the following pathologies: grade II diffuse astrocytoma, glioblastoma, hemangioblastoma, and metastatic adenocarcinoma (lung or breast primary). Average percent reactivity was recorded as a mean observed in ten high-power fields. The following scale was used to grade immunoreactivity: 0 = immunonegative, 1 = 1–25% reactive, 2 = 26–50% reactive, 3 = 51–75% reactive, 4 = 76–100% reactive. ResultsWhile we did not observe nuclear expression of β-catenin in any samples, there was uniform cytoplasmic expression of β-catenin within glial tumor cells. There was a clear distinction in tumor endothelial cells whereby diffuse staining was noted in areas of microvascular hyperplasia in GBM and a less immunoreactive profile in low-grade astrocytomas. By contrast, non-glial tumors, contained very minimal cytoplasmic β-catenin expression in tumor and stromal cells and were devoid of immunoreactivity in endothelial cells. Conclusionβ-catenin is unique marker of proliferating endothelial cells in GBM. Therapies targeting the spatial and structural heterogeneity inherent to GBM may prove to be efficacious and result in an improved survivorship.

Beyond Glioma: The Utility of Radiomic Analysis for Non-Glial Intracranial Tumors

Simple SummaryTumor qualities, such as growth rate, firmness, and intrusion into healthy tissue, can be very important for operation planning and further treatment. Radiomics is a promising new method that allows the determination of some of these qualities on images performed before surgery. In this article, we provide a review of the use of radiomics in various tumors of the central nervous system, such as metastases, lymphoma, meningioma, medulloblastoma, and pituitary tumors.The field of radiomics is rapidly expanding and gaining a valuable role in neuro-oncology. The possibilities related to the use of radiomic analysis, such as distinguishing types of malignancies, predicting tumor grade, determining the presence of particular molecular markers, consistency, therapy response, and prognosis, can considerably influence decision-making in medicine in the near future. Even though the main focus of radiomic analyses has been on glial CNS tumors, studies on other intracranial tumors have shown encouraging results. Therefore, as the main focus of this review, we performed an analysis of publications on PubMed and Web of Science databases, focusing on radiomics in CNS metastases, lymphoma, meningioma, medulloblastoma, and pituitary tumors.

BIBLIOMETRIC ANALYSIS OF THE SCIENTIFIC LITERATURE ON MENINGIOMAS WITH CALCIFICATION

Meningiomas are the most common non-glial tumours of the central nervous system characterized by pathological biomineralization. The work aimed to conduct bibliometric analysis and systematize data on the prevalence, etiology, morphology and main trends in the study of meningiomas with calcification. The authors searched for information on meningiomas in electronic databases such as PubMed, Scopus, Web of Science and Google Scholar for the past 25 years by the key terms such as meningiomas, calcifications, and psammoma bodies. For bibliometric analysis, the authors used an online platform to monitor and analyze international research using visualization tools and modern citation metrics SciVal (Scopus) and a tool for building and visualizing bibliometric networks VOSviewer. Pathological biomineralization is manifested through the formation of psammoma bodies, and the main mineral component is calcium hydroxyapatite. Although calcification is likely to play a protective role and be a favourable prognostic feature, it should be considered when choosing surgical tactics. There is also the problem of closing the defects of the dura mater with the help of biological and synthetic transplants. According to the bibliometric analysis of scientific literature on meningiomas and the phenomena of pathological biomineralization in them, we found that the number of publications on this topic had increased significantly over the past five years, the leading countries of origin are the United States, Japan and China. When researching the array of Scopus database publications using SciVal tools, the problem of meningioma calcification was divided into 61 topics and 24 thematic clusters, the vast majority of which belonged to medicine and biology and materials science. According to the results of bibliometric analysis of 678 publications in the Scopus database by keywords "calcification" and "meningioma", they can be divided into seven thematic clusters and four chronological stages. Despite the prevalence of meningioma calcification, there is currently no fundamental idea of ​​the etiology and pathogenesis of this process. Studying the morphological features of meningiomas with calcification can help improve the diagnosis and treatment of the central nervous system tumours.

Pattern of use of intraoperative ultrasound in surgery for brain tumors influences outcomes in glial tumors.

Background Intraoperative ultrasound (iUS) imaging has emerged as a promising adjunct in glioma surgery with both, 2-dimensional (2D) as well as navigated 3-dimensional (n3D), modes increasingly being used. Methods We analyzed our decade-long experience of 1075 brain tumor (807, 75% gliomas) cases operated using iUS. A retrospective chart and electronic records review was performed. The primary aim was to understand the patterns of use of iUS mode and its purpose of application (as a localizing tool or as a resection control modality) as well as to evaluate its impact on the extent of resection. Results The use of iUS increased over time, especially with the introduction of n3DUS though 2DUS remained the more commonly used mode (63%) overall during this period. For biopsies (156 cases), both 2D, as well as n3D iUS, were used as a localizing tool only. Lesion localization was the major purpose for use of iUS even for tumor resections (61%). Resection control was performed more often for gliomas (46.5% compared to 16.5% in non-glial tumors). n3DUS was the preferred modality as a resection control tool irrespective of histological class. GTR (gross total resection) was achieved in 53.1% cases overall, while in glial and non-glial tumors it was 44.7% and 80.7%, respectively. GTR was higher when iUS was used as a resection control modality. The US and MR defined EOR (extent of resection) showed substantial agreement (κ = 0.678) with high diagnostic accuracy of 84% for glial tumors. In glial tumors, iUS was used more often in eloquent tumors and GTR rates were slightly higher than when iUS was not used. Conclusion iUS is a versatile tool and is a useful surgical adjunct for glioma surgeons. Besides its proven benefit as a localizing tool, when used as a tool for resection control it improves the resection rates. n3DUS may offer benefits over 2DUS as a resection control modality, though the evidence is still evolving.

Triphasic dysnatremia complicated by generalized convulsions following craniopharyngioma resection in a pediatric patient

Craniopharyngiomas are benign epithelial tumors arising from craniopharyngial duct. Although rare, these are the most common suprasellar, non-glial tumors in children constituting about 50% of all sellar / suprasellar tumors. The management of these tumors can be very challenging not only periopratively but also in postoperative phase as it can lead to extremes of dysnatremias ranging from central diabetes incipidus (CDI), syndrome of inappropriate anti diuretic hormone (SIADH) to cerebral salt wasting syndrome (CSWS). We present a triphasic sodium imbalance following craniopharyngioma resection complicated by generalized convulsions.