The introduction of computed tomography (CT) myelography for spinal diseases has allowed the diagnosis of several intradural and extradural etiologies. With the advent of water-soluble, nonionic contrast agents, the safety and availability of this technique have expanded. Although magnetic resonance imaging (MRI) has faded the indications for CT myelography, some specific conditions and settings still benefit from the functional flow of contrast in the subarachnoid space and/or the patient's particular limitations in performing MRI (especially in the presence of intense metallic artifacts). We present the case of a 23-year-old male patient who underwent long-term follow-up for an intramedullary epidermoid cyst. At the time of diagnosis, the patient complained of right lower limb tremor and pain, which progressed to leg weakness, with no congenital abnormality. His first surgery resulted in a mass resection without spinal fixation. Three years later, thoracic canal stenosis and kyphosis were diagnosed, leading to a second surgery, consisting of laminectomy and cervicothoracic fixation. At 8 years of age, worsening weakness and sphincter issues prompted further evaluations. CT myelography revealed upper thoracic cord enlargement. An intramedullary epidermoid cyst was diagnosed, and the patient underwent a new gross total resection. CT myelography is not obsolete. Patients requiring spine imaging for oncologic control and/or new or worsening neurological symptoms may benefit from CT myelography when standard spine MRI cannot be performed. Epidermoid cysts require long-term postoperative follow-up, as recurrence may occur years after surgical resection owing to their indolent, benign behavior.

BACKGROUND:Medulloblastoma (MB) is the most common malignant brain tumor in children. Although the 5-year survival rate is approximately 70-80%, the current standard treatment results in severe and long-term side effects. The search for new anticancer immunotherapeutic targets has identified B7-H3 as a promising candidate in various solid tumors. However, the role of B7-H3 in MB remains unclear, and studies reporting its protein expression and association with clinicopathological characteristics are still limited. METHODS:In this study, B7-H3 protein expression was evaluated by immunohistochemistry in seven non-tumor samples and 43 molecularly characterized MB tissues. Its expression profile was correlated with B7-H3 (CD276) mRNA levels, which were previously determined by nCounter, as well as with the patients' clinical features. RESULTS:Only 14.3% (1/7) of non-tumor brain and cerebellum tissues showed B7-H3 positivity, whereas 95.6% (41/43) of the MB samples expressed this protein at distinct levels. B7-H3 was found in the cytoplasm and on the membrane of cancer cells. A significant positive correlation was observed between CD276 mRNA and B7-H3 protein levels. Moreover, high expression of B7-H3 protein was associated with worse overall survival and the presence of metastasis at diagnosis. CONCLUSIONS:This is the first study to associate CD276 mRNA and B7-H3 protein levels in MB, revealing a significant positive correlation. We observed that B7-H3 was overexpressed in MB compared to non-tumor brain tissue. High B7-H3 expression was associated with a worse outcome and with the presence of metastasis at diagnosis.

Medulloblastoma (MB) is the most prevalent malignant brain tumor in children, known for its heterogeneity and treatment-associated toxicity, and there is a critical need for new therapeutic targets. We analyzed the somatic mutation profile of 15 driver genes in 69 Latin-Iberian molecularly characterized medulloblastomas using the Illumina TruSight Tumor 15 panel. We classified the variants based on their clinical impact and oncogenicity. Among the patients, 66.7% were MBSHH, 13.0% MBWNT, 7.3% MBGrp3, and 13.0% MBGrp4. Among the 63 variants found, 54% were classified as Tier I/II and 31.7% as oncogenic/likely oncogenic. We observed 33.3% of cases harboring at least one mutation. TP53 (23.2%, 16/69) was the most mutated gene, followed by PIK3CA (5.8%, 4/69), KIT (4.3%, 3/69), PDGFRA (2.9%, 2/69), EGFR (1.4%, 1/69), ERBB2 (1.4%, 1/69), and NRAS (1.4%, 1/69). Approximately 41% of MBSHH tumors exhibited mutations, TP53 (32.6%) being the most frequently mutated gene. Tier I/II and oncogenic/likely oncogenic TP53 variants were associated with relapse, progression, and lower survival rates. Potentially actionable variants in the PIK3CA and KIT genes were identified. Latin-Iberian medulloblastomas, particularly the MBSHH, exhibit higher mutation frequencies than other populations. We corroborate the TP53 mutation status as an important prognostic factor, while PIK3CA and KIT are potential therapeutic targets.

The presence of dysmorphic neurons with strong cytoplasmatic accumulation of heavy non-phosphorylated neurofilament is crucial for the diagnostics of focal cortical dysplasia type II (FCDII). While ILAE's classification describes neocortical dysplasias, some groups have reported patients with mesial t abnormal neurons in the hippocampus of mesial temporal lobe epilepsy. Here we report a patient with such abnormal neurons in the hippocampus and compared it with previous reports of hippocampal dysplasia. Finally, we discuss the need for diagnostic criteria of hippocampal dysplasia.

PurposeMedulloblastomas are the most common primary malignant brain tumors in children. They are divided into molecular subgroups: WNT-activated, SHH-Activated, TP53 mutant or wild type, and non-WNT/non-SHH (Groups 3 and 4). WNT-activated medulloblastomas are usually caused by mutations in the CTNNB1 gene (85%–90%), and most remaining cases of CTNNB1 wild type are thought to be caused by germline mutations in APC. So far, the frequencies of CTNNB1 have been reported mainly in North American and European populations. The aim of this study was to report the frequency of CTNNB1 mutations in WNT-activated medulloblastomas in a Latin-Iberian population and correlate with their clinicopathological characteristics.MethodsA total of 266 medulloblastomas from seven different institutions from Brazil (n=211), Portugal (n=38), and Argentina (n=17) were evaluated. Following RNA and DNA isolation from formalin-fixed, paraffin-embedded (FFPE) tumor tissues, the molecular classification and CTNNB1 mutation analysis were performed by nCounter and Sanger sequencing, respectively.ResultsWNT-activated medulloblastomas accounted for 15% (40/266) of the series. We observed that 73% of WNT-activated medulloblastomas harbored CTNNB1 mutations. CTNNB1 wild-type cases (27%) were more prevalent in female individuals and suggested to be associated with a worse outcome. Among the CTNNB1 wild-type cases, the available analysis of family history revealed two cases with familiar adenomatous polyposis, harboring APC germline variants.ConclusionWe observed a lower incidence of CTNNB1 mutations in WNT-activated medulloblastomas in our Latin-Iberian cohort compared to frequencies previously described in other populations. Considering that CTNNB1 wild-type cases may exhibit APC germline mutations, our study suggests a higher incidence (~30%) of hereditary WNT-activated medulloblastomas in the Latin-Iberian population.

Pilocytic astrocytoma is a central nervous system tumor of slow growth, which represents 5 % of all gliomas and most often develops in the cerebellum (42-60 %), but can also arise in other neural areas, such as the optic pathway or hypothalamus (9-30 %); brainstem (9 %); spinal cord (2 %). In the pediatric population, this tumor is the second most common cause of neoplasms and, on the other hand, in adults, it is often rare, probably due to its aggressiveness in these individuals. Studies reveal that the origin of pilocytic astrocytoma is characterized by a fusion between the BRAF gene and the KIAA1549 locus, and the application of the immunohistochemistry technique for the analysis of BRAF protein expression can be a valuable tool for diagnostic purposes. Due to the relative rarity of this disease in adults, there are few publications on the most effective diagnostic and treatment strategies for this tumor. The general objective of this study was to analyze the histopathological and immunohistochemical characteristics of pilocytic astrocytoma in these patients. For this, a retrospective study of patients aged over 17 years with a diagnosis of pilocytic astrocytoma was carried out at the Department of Pathology of UNIFESP/EPM, from 1991 to 2015. In order to define BRAF positivity in the immunohistochemical analysis, at least three consecutive fields with more than 50 % immunostaining were used as criteria and, thus, it was inferred that the 7 cases analyzed were considered positive for the cytoplasmic marker BRAF V600E. Histopathological analysis associated with BRAF immunostaining is of paramount importance as a diagnostic method in these cases. However, future molecular studies will be necessary both for a better understanding of the aggressiveness and prognostic of this tumor and for research involving specific therapies for pilocytic astrocytoma in adults.

Pilocytic astrocytoma is the most common primary CNS neoplasm in children and adolescents, rare after the first two decades of life. While some authors report a favorable prognosis in the adult age group with the tumor, others have associated it with higher mortality. The molecular alteration most observed in cases of pilocytic astrocytoma in the pediatric group is the BRAF-KIAA1549 gene fusion, and there are still few studies confirming the presence of this fusion in the adult population. This work investigated genetic alterations involving the 7q34 region in BRAF gene in 21 adult individuals with pilocytic astrocytoma, by FISH. In addition, was identified the immunohistochemical expression of BRAFV600E, correlating these findings with histopathological and clinical ones. BRAF-KIAA1549 fusion appeared in only one case, while in two other cases were found deletions related to the FAM131B-BRAF fusion, suggesting that maybe the latter is more frequently in this population. Through the evaluation of immunoreactivity, 71% of the cases were considered positive and 29% negative. Cases considered positive for BRAFV600E immunoreactivity can potentially be treated through drug therapy with BRAF inhibitors; however, it is always recommended to carry out a molecular study for diagnostic confirmation. This is the first Brazilian study that aimed to investigate possible genetic alterations in the BRAF gene in pilocytic astrocytomas, specifically in adults. Only 1 patient died, but due to operative complications and not the disease itself, suggesting a good evolution of these individuals.

With the current pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), measures of social isolation were necessary, and this resulted in the interruption of several treatments. Regarding neuro-oncological patients, especially those with central nervous system (CNS) disorders, this interruption can cause serious damage or even compromise the success of the treatment in the future. It is essential that each case be evaluated separately to decide how to continue treatment during the pandemic, always considering the risk of SARS-CoV-2 infection and the benefits that the treatment will bring. The policy of not prescribing potentially toxic drugs, chemotherapy, and immunosuppressive therapies, as well as the use of techniques like stereotactic biopsy and telemedicine are important strategies at this time.

Supplementary Data from EGFRvIII Deletion Mutations in Pediatric High-Grade Glioma and Response to Targeted Therapy in Pediatric Glioma Cell Lines

Pilocytic astrocytomas are the primary tumors most found in the first two decades of life, accounting for around 15% of all brain tumors. Research at the molecular level of pilocytic astrocytoma makes possible to compose an overview of what is known about the origin and development of the tumor. It is known that there are alterations in the Mitogen Activated Protein Kinase (MAPK) signaling pathway that are important auxiliary markers in diagnosis. This study seeks to list the main points about the involvement of this pathway in tumor formation in pilocytic astrocytoma. A review was conducted in search of published studies available in NCBI, PubMed, MEDLINE, Scielo and Google Scholar. The most frequent alteration is the gene fusion between BRAF and KIAA1549 genes, found in approximately 90% of pediatric cases. The second most common event is the BRAFV600E mutation, also often found in children than in adult cases. The molecular origin of pilocytic astrocytomas is related to alterations in the MAPK pathway, which acts with several functions in the brain such as memory formation, pain perception, induction of cortical neurogenesis, and midbrain and cerebellum development. Alterations in this pathway can be therapeutic targets in the treatment of patients with pilocytic astrocytoma. The MAPK pathway is extremely important and knowledge about its involvement in astrocytic tumors is essential for a better approach to the patient.

Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), which usually affects young adults between 20 and 40 years old. In chronic neurodegenerative diseases such as multiple sclerosis, CNS cells take on several adaptations during neuroinflammation. The main cells involved in this inflammatory process are the glial cells, in which the astrocytes stand out. These cells play a complex role, and several studies report that reactive astrocytes lose their supporting role and gain toxic function in the progression of these diseases. Results: The beneficial and injurious effects of this group of cells in MS are addressed in this work, as well as some drugs that are already used in the treatment of patients with multiple sclerosis, aiming to regulate astrocytic activities. Conclusions: The knowledge about the functions of astrocytes is essential for the expansion of scientific research in this area, since these cells are so important and involved in different mechanisms of action, especially in neurodegenerative and autoimmune diseases.

A 49-year-old man presented to the emergency depart-ment after cranioencephalic trauma with an intraventricular tumor detected in the computed tomography (

Medulloblastoma is the most frequent pediatric malignant brain tumor, and is divided into four main subgroups: WNT, SHH, group 3, and group 4. MYCN amplification is an important medulloblastoma prognostic biomarker. We aimed to molecular classify and predict MYCN amplification in a single assay. It was included 209 medulloblastomas from 205 patients (Brazil, Argentina, and Portugal), divided into training (n = 50) and validation (n = 159) sets. A nCounter assay was carried out using a custom panel for molecular classification, with additional genes, including MYCN. nSolver 4.0 software and the R environment were used for profiling and MYCN mRNA analysis. MYCN amplification by FISH was performed in 64 cases. The 205 medulloblastomas were classified in SHH (44.9%), WNT (15.6%), group 3 (18.1%) and group 4 (21.4%). In the training set, MYCN amplification was detected in three SHH medulloblastomas by FISH, which showed significantly higher MYCN mRNA counts than non-FISH amplified cases, and a cutoff for MYCN amplification was established ( $$\overline{X }$$ + 4σ = 11,124.3). Applying this threshold value in the validation set, we identified MYCN mRNA counts above the cutoff in three cases, which were FISH validated. We successfully stratified medulloblastoma molecular subgroups and predicted MYCN amplification using a single nCounter assay without the requirement of additional biological tissue, costs, or bench time.

Objectives: In this review, the main histological and molecular characteristics of meningiomas will be addressed, as well as the aspects most related to clinical conditions, treatment, and survival of patients, enabling a better understanding of these tumors behavior. Methods: This study was conducted with the search for published studies available on NCBI, PubMed, MEDLINE, Scielo and Google Scholar. Relevant documents have been identified and 50 articles were selected. Results: The main points about meningiomas were characterized, as well as the histological presence of spontaneous necrosis in grade I and brain invasion as diagnostic criteria, their molecular origin related to deletion of chromosome 22 and mutations in theNF2 and TERT genes, in addition to their clinical characteristics. The preferential treatment remains the total resection of the tumor. Conclusion: The information about meningiomas is well known and necessary, but it is expected that more work will emerge related to the behavior of these tumors, and that the scientific community will obtain more clarity about the best ways to conduct the patients treatment.

Late radiation necrosis is a rare entity presenting in 2.2% to 9% of radiation-treated arteriovenous malformations (AVMs). It occurs by a mean of 3 years following treatment. There are few reports in the literature of radionecrosis and solid lesions treated with surgery.1-4 To the authors' knowledge, this case has the longest interval between radiosurgery and the presentation of cerebral necrosis. In this surgical video, we present the case of a 51-year-old female with a left supramarginal gyrus AVM that received radiosurgery with gamma knife; after 20 years, she began having seizures and aphasia. The magnetic resonance imaging scan revealed a lesion simulating an intra-axial tumor causing important edema and mass effect. Medical treatment was given including high-dose steroids without success, therefore microsurgery was performed. The surgery was presented in a step-by-step basis and correlation was performed with the involved adjacent anatomy, to illustrate the anatomy of the approach and surgical landmarks. The patient's symptoms resolved completely, and the postoperative magnetic resonance imaging scan showed complete resection and resolution of the edema. The histopathological findings were consistent with a radionecrosis and AVM. The patient signed the Institutional Consent Form, which states that she accepts the procedure and allows the use of her images and videos for any type of medical publications in conferences and/or scientific articles.

ABSTRACT Background: Cancer patients in general and glioblastoma patients, in particular, have an increased risk of developing complications from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and reaching a balance between the risk of exposure to infection and the clinical benefit of their treatment is ideal. The aggressive behavior of this group of tumors justifies the need for a multidisciplinary team to assist in clinical decisions during the current pandemic. Brazil is now ranked #2 in the number of cases and deaths from COVID-19 pandemic, and existing disparities in the treatment of neuro-oncology patients in Brazil will challenge the clinical and surgical decisions of this population, possibly affecting global survival. Objective: To search the literature about the management of glioblastomas during COVID-19 pandemic to guide surgical and clinical decisions in this population of patients in Brazil. Methods: We performed a systematic search on the PubMed electronic database targeting consensus statements concerning glioblastoma approaches during COVID-19 pandemic up to July 18, 2020. Results: When approaching glioblastoma during the COVID-19 pandemic, important parameters that help in the decision-making process are age, performance status, tumor molecular profile, and patient consent. Younger patients should follow the standard protocol after maximal safe resection, mainly those with MGMT methylated tumors. Aged and underperforming patients should be carefully evaluated, and probably a monotherapy scheme is to be considered. Centers are advised to engage in telemedicine and to elaborate means to reduce local infection. Conclusion: Approaching glioblastoma during the COVID-19 pandemic will be challenging worldwide, but particularly in Brazil, where a significant inequality of healthcare exists.

Background Angiogenesis is one of the hallmarks of cancer. This complex mechanism of tumor progression provides tumors cells with essential nutrients. There have been a limited number of investigations of markers of angiogenesis in Glioblastomas (GBMs), and most previous studies have focused on VEGF-A. Recent evidence suggests that there is a complex lymphatic system in central nervous system (CNS), which suggests VEGF-C and VEGF–D as interesting biomarker candidates. This study was designed to evaluate the expressions of VEGF-A, −C, −D and their co-receptors, VEGFR-1, VEGFR-2, and VEGFR-3 by immunohistochemistry (IHC) using a series of GBMs. In addition, we evaluate any putative correlations between IHC expression levels of VEGF and clinical data of patients. Methods Tumor samples of 70 GBM patients (64 isocitrate dehydrogenase-1 wildtype (wtIDH-1) and 6 mutant (mutIDH-1)) were assessed by IHC using tissue microarray platforms for VEGF subunits and their co-receptors. The medical records were reviewed for clinical and therapeutic data. Results All VEGF subunits and receptors were highly expressed in GBMs: 57 out of 62 (91.9%), 53 out of 56 (94.6%) and 55 out of 63 cases (87.3%) showed VEGF-A, VEGF-C and -D imunoexpression, respectively. Interestingly, we had found both nuclear and cytoplasmic localization of VEGF-C staining in GBM tumor cells. The frequency of immunoexpression of VEGF receptors was the following: VEGFR-1, 65 out of 66 cases (98.5%); VEGFR-2, 63 out of 64 cases (98.4%); VEGFR-3, 49 out of 50 cases (90.0%). There were no significant differences in the patient overall survival (OS) related to the VEGF staining. A weak and monotonous correlation was observed between VEGF and its cognate receptors. The pattern of VEGF IHC was found to be similar when GBM mutIDH-1 subtypes were compared to wtIDH-1. Conclusion Both VEGF-C and –D, together with their receptors, were found to be overexpressed in the majority GBMs, and the IHC expression levels did not correlate with OS or IDH status. To understand the significance of the interactions and increased expression of VEGF-C, VEGF-D, VEGFR-2, and VEGFR-3 axis in GBM requires more extensive studies. Also, functional assays using a larger series of GBM is also necessary to better address the biological meaning of nuclear VEGF-C expression in tumor cells.

Medulloblastoma (MB) is the most common malignant brain tumor in children. It is currently classified in four main molecular subgroups with different clinical outcomes: sonic hedgehog, wingless, group 3, and group 4 (MBSHH, MBWNT, MBGRP3, or MBGRP4). Presently, a 22-gene expression panel has been efficiently applied for molecular subgrouping using nCounter technology. In this study, formalin-fixed, paraffin-embedded samples from 164 Brazilian medulloblastomas were evaluated, applying the 22-gene panel, and subclassified into the low and high expression of nine key medulloblastoma-related genes. In addition, TP53 mutation status was assessed using TruSight Tumor 15 Panel, and its correlation with expression and prognostic impact was evaluated. Samples from 149 of 164 patients (90%) were classified into MBSHH (47.7%), MBWNT (16.1%), MBGRP3 (15.4%), and MBGRP4 (20.8%). GNAS presented the highest expression levels, with higher expression in MBSHH. TP53, MYCN, SOX2, and MET were also up-regulated in MBSHH, whereas PTEN was up-regulated in MBGRP4. GNAS, TP53, and PTEN low expression was associated with the unfavorable patient outcome only for MBSHH (P = 0.04, P = 0.01, and P = 0.02, respectively). TP53 mutations were detected in 28.57% of MBSHH cases and exhibited association with lower expression and worse clinical outcome, although not statistically significant. The 22-gene panel for molecular classification of medulloblastoma associated with the expression of GNAS, TP53, and PTEN improves the patient prognostication in MBSHH subgroup and can be easily incorporated in the 22-gene panel without any additional costs.