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PURPOSE: This study aims to provide an exhaustive analysis of pediatric low-grade gliomas (pLGGs) in the cerebellar hemispheres, focusing on incidence, clinical characteristics, surgical outcomes, and prognosis. It seeks to enhance understanding and management of pLGGs in the pediatric population. METHODS: We conducted an observational, descriptive, retrospective, and cross-sectional study at a pediatric hospital, reviewing medical records of 30 patients with cerebellar hemispheric pLGGs treated from December 2014 to January 2023. Data collection included demographics, clinical presentation, imaging findings, surgical approach, postoperative complications, histopathological diagnosis, hydrocephalus management, and follow-up. Molecular markers and adjuvant therapies were also analyzed. RESULTS: The cohort predominantly presented with cerebellar symptoms, with 60% showing hydrocephalus at diagnosis. MRI with gadolinium was crucial for diagnosis. Surgical focus was on achieving gross total resection (GTR), accomplished in 70% of cases. Postsurgical hydrocephalus was less common, and cerebellar mutism was not reported. While a complete molecular analysis was not performed in all cases, available data suggest significant influence of molecular markers on prognosis and therapeutic options of pLGGs. CONCLUSIONS: This study highlights the unique clinical and molecular characteristics of cerebellar hemispheric pLGGs in children. The lower incidence of postoperative hydrocephalus and absence of cerebellar mutism are notable findings. Emphasizing a multidisciplinary approach, our findings contribute to a deeper understanding of pediatric pLGGs, underscoring the need for personalized treatment strategies and vigilant follow-up.

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Tectal gliomas represent a subset of low-grade tumors that arise in the tectal region at the roof of the brainstem. Symptoms of tectal glioma include those caused by increased intracranial pressure due to obstructive hydrocephalus. Headache, blurred vision, double vision, nausea and vomiting are common symptoms. In the treatment, ETV (endoscopic third ventriculostomy) or VP-shunt (ventriculoperitoneal) can be applied to treat hydrocephalus. Tectal gliomas are usually diagnosed in childhood and often occur in adults. They are often benign, slowly progressing lesions; outpatient clinical and radiological follow- up is sufficient. We present two cases of pediatric patients with mesencephalic tectal plate tumors. An 11-year-old boy and a 15-year-old girl applied to the Emergency Department with different complaints. The 11 year-old-boy was treated with VP-shunt due to acute hydrocephalus.

Los gliomas tectales representan un subtipo de tumores de bajo grado que se desarrollan en la región tectal, en la parte superior del tronco encefálico. Los síntomas incluyen los causados por el aumento de la presión intracraneal por hidrocefalia obstructiva. Son comunes la cefalea, la visión borrosa o doble, las náuseas y los vómitos. El tratamiento de la hidrocefalia es la ventriculostomía endoscópica del tercer ventrículo o la derivación ventrículo-peritoneal. Los gliomas tectales se diagnostican habitualmente en la infancia, pero son frecuentes también en adultos. En general son benignos y de progresión lenta; es suficiente el seguimiento ambulatorio clínico y radiológico. Se presentan dos pacientes pediátricos con tumores de la placa tectal mesencefálica. Un niño de 11 años y una niña de 15 años concurrieron al Departamento de Emergencias con diferentes síntomas. El niño fue tratado con derivación ventrículo-peritoneal por hidrocefalia aguda.

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Diffuse gliomas are tumors that arise from glial or glial progenitor cells. They are currently classified as astrocytoma isocitrate dehydrogenase (IDH)-mutant or oligodendroglioma IDH-mutant, and 1p/19q-codeleted, both slower-growing tumors, or glioblastoma (GBM), a more aggressive tumor. Despite advances in the diagnosis and treatment of gliomas, the median survival time after diagnosis of GBM remains low, approximately 15 months, with a 5-year overall survival rate of only 6.8%. Therefore, new biomarkers that could support the earlier diagnosis and prognosis of these tumors would be of great value. MUC17, a membrane-bound mucin, has been identified as a potential biomarker for several tumors. However, the role of this mucin in adult gliomas has not yet been explored. Here, we show for the first time, in a retrospective study and by in silico analysis that MUC17 is one of the relevant mutant genes in adult gliomas. Moreover, that an increase in MUC17 methylation correlates with an increase in glioma malignancy grade. Patients with MUC17 mutations had a poorer prognosis than their wild-type counterparts in both GBM and non-GBM glioma cohorts. We also analyzed mutational profiles that correlated strongly with poor survival. Therefore, in this study, we present a new potential biomarker for further investigation, especially for the prognosis of adult diffuse gliomas.

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High-grade gliomas (HGG) are the most common primary brain malignancies and account for more than half of all malignant primary brain tumors. The new 2021 WHO classification divides adult HGG into four subtypes: grade 3 oligodendroglioma (1p/19 codeleted, IDH-mutant); grade 3 IDH-mutant astrocytoma; grade 4 IDH-mutant astrocytoma, and grade 4 IDH wild-type glioblastoma (GB). Radiotherapy (RT) and chemotherapy (CTX) are the current standard of care for patients with newly diagnosed HGG. Several clinically relevant molecular markers that assist in diagnosis and prognosis have recently been identified. The treatment for recurrent high-grade gliomas is not well defined and decision-making is usually based on prior strategies, as well as several clinical and radiological factors. Whereas the prognosis for GB is grim (5-year survival rate of 5-10%) outcomes for the other high-grade gliomas are typically better, depending on the molecular features of the tumor. The presence of neurological deficits and seizures can significantly impact quality of life.

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Astroblastoma is a rare astrocytic glial neoplasm that affects mainly young girls, peaking between 10 and 30 years of age, with low- and high-grade manifestations. Imaging characteristics are well-described, but histopathologic and, more recently, molecular analysis is fundamental to establish the diagnosis, now based on MN1 alterations. We describe a case with typical imaging and histologic features of an MN1-altered astroblastoma.

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Retinoblastoma-binding protein 8 (RBBP8) affects the prognosis of patients with malignancies through various mechanisms. However, its function in gliomas is unknown. Our study explored the effects of RBBP8 on the prognosis of glioma patients, as well as its regulatory role in the glioma immune microenvironment. We used various bioinformatics methods to analyze the transcriptional profiles and methylation data of RBBP8 in gliomas from multiple databases. Our results showed that the mRNA and protein expression of RBBP8 in gliomas was higher than that in normal tissues and positively correlated with malignant clinical features such as age and WHO grade. A Kaplan-Meier analysis showed that patients with high RBBP8 expression had a poor prognosis. Cox regression demonstrated that RBBP8 was an independent risk indicator and had good diagnostic value for the poor prognosis of glioma. Importantly, RBBP8 was positively correlated with many well-known immune checkpoints (e.g., CTLA4 and PDL-1). Finally, a gene set enrichment analysis revealed that RBBP8 was remarkably enriched in cancer-related pathways such as cell cycle, DNA replication and so on. In conclusion, this study is the first to elaborate on the value of RBBP8 in the pathological process of glioma for anti-tumor immunotherapy. In addition, the expression of RBBP8 and its methylation site, cg05513509, may provide potential targets for glioma therapy.

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Fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) is used to assist brain tumor resection, especially for high-grade gliomas but also for low-grade gliomas, metastasis, and meningiomas. With the increasing use of this technique, even to assist biopsies, high-grade glioma-mimicking lesions had misled diagnosis by showing 5-ALA fluorescence in non-neoplastic lesions such as radiation necrosis and inflammatory or infectious disease. Since only isolated reports have been published, we systematically review papers reporting non-neoplastic lesion cases with 5-ALA according with the PRISMA guidelines, present our series, and discuss its pathophysiology. In total, 245 articles were identified and 12 were extracted according to our inclusion criteria. Analyzing 27 patients, high-grade glioma was postulated as preoperative diagnosis in 48% of the cases. Microsurgical resection was performed in 19 cases (70%), while 8 patients were submitted to biopsy (30%). We found 4 positive cases in demyelinating disease (50%), 4 in brain abscess (80%), 1 in neurocysticercosis (33%), 1 in neurotoxoplasmosis, infarction, and hematoma (100%), 4 in inflammatory disease (80%), and 3 in cortical dysplasia (100%). New indications are being considered especially in benign lesion biopsies with assistance of 5-ALA. Using fluorescence as an aid in biopsies may improve procedure time, number of samples, and necessity of intraoperative pathology. Further studies should include this technology to encourage more beneficial uses.

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Gliomas are primary intracranial tumors with defined molecular markers available for precise diagnosis. The prognosis of glioma is bleak as there is an overlook of the dynamic crosstalk between tumor cells and components of the microenvironment. Herein, different phases of gliomagenesis are presented with reference to the role and involvement of secreted proteomic markers at various stages of tumor initiation and development. The secreted markers of inflammatory response, namely interleukin-6, tumor necrosis factor-α, interferon-ϒ, and kynurenine, proliferation markers human telomerase reverse transcriptase and microtubule-associated-protein-Tau, and stemness marker human-mobility-group-AThook-1 are involved in glial tumor initiation and growth. Further, hypoxia and angiogenic factors, heat-shock-protein-70, endothelial-growth-factor-receptor-1 and vascular endothelial growth factor play a major role in promoting vascularization and tumor volume expansion. Eventually, molecules such as matrix-metalloprotease-7 and intercellular adhesion molecule-1 contribute to the degradation and remodeling of the extracellular matrix, ultimately leading to glioma progression. Our study delineates the roadmap to develop and evaluate a non-invasive panel of secreted biomarkers using liquid biopsy for precisely evaluating disease progression, to accomplish a clinical translation.

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Gliomas represent 80% of all primary malignant brain tumors in adults. In view of this public health problem, the early detection through sensitive and specific molecular tumor markers analysis can help to improve gliomas diagnosis and prognosis as well as their staging, assessment of therapeutic response and detection of recurrence. Therefore, this review focuses in current gliomas tumor markers, IDH-1/2, 1p/19q, MGMT, ATRX, TERT, H3, EGFR, BRAF and Ki67 used in clinic worldwide and their importance to early detection, glioma histological and molecular classification as well as in predicting patient's therapeutic response. In addition, we present what are the steps in the requesting process for this type of examination in the Brazilian Public Health System (SUS) scope, which attends most of the Brazilian population. Thereby, this article is useful in demonstrating which markers are used in the clinical practice for glioma patients and can be performed in the SUS through partnerships/agreements between specialized health centers and clinical analysis laboratories. It is hoped that this work clarifies, the necessary subsidies to carry out the research of tumor markers in all institutions that serve SUS users, providing a service with equal conditions.

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The utilization of the different molecular techniques for the diagnosis of gliomas according to the WHO classification is still not available to everyone in our country. Our objective was to describe the diagnostic algorithm developed based on available resources, in accordance with the current classification (2021). Also, to describe the epidemiological profile of gliomas diagnosed between 2018-2021 at the Roffo Institute and compare it with the international literature. IDH1-R132H and ATRX mutation, as well as 1p19q status, CDKN2A, EGFR, and p53 were evaluated. 94 patients were included, 53.2% were male, with a mean age of 50.9 years. The most frequent diagnosis was GB IDH1-wild type (63.8%). Considering only grade 2 and 3 gliomas, diffuse astrocytoma IDH1-Mutated / ATRX-Mutated / p53-overexpressed, grade 2 (11.7%) was the most frequent diagnosis. Regarding their location, 67% of the tumors were located in the neocortical telencephalon: 24.5% of the total in the frontal lobe. In 95.7% of cases, a conclusive integrated diagnosis was reached following the proposed algorithm. The epidemiological characteristics coincide with what has been published in the literature. Molecular biology allowed us to clearly differentiate pathologies that we assumed were related from a histological point of view, but which, observing their natural history, their genetics and their response to established treatments were different tumors, although they were all called "gliomas". International standards do not conceive CNS tumor diagnosis without molecular biology. It is not acceptable to continue to diagnose only with histological standards. The proposed algorithm could be a viable and reliable alternative.

La aplicación de las diferentes técnicas moleculares para el diagnóstico de los gliomas según la clasificación de la OMS, sigue sin estar al alcance de todos en nuestro país. Nuestro objetivo fue describir el protocolo diagnóstico desarrollado en función de los recursos disponibles, conforme con la clasificación vigente (2021). También, describir el perfil epidemiológico de los gliomas diagnosticados entre 2018-2021 en el Instituto Roffo y contrastarlo con la literatura. Se evaluó la mutación en IDH1-R132H, ATRX, el estado del 1p19q, CDKN2A, EGFR y del p53. Se incluyeron 94 pacientes, 53.2% fueron masculinos, con una edad promedio de 50.9 años. El diagnóstico más frecuente fue el de GB IDH1-no mutado (63.8%). Considerando únicamente a los gliomas grado 2 y 3, el astrocitoma difuso IDH1-Mutado/ATRX-Mutado/p53-sobreexpresado, grado 2 (11.7%) fue el más frecuente. En cuanto a su localización, el 67% de los tumores se ubicaron en el telencéfalo neocortical: 24.5% del total en el lóbulo frontal. En el 95.7% de los casos se arribó a un diagnóstico integrado concluyente siguiendo el algoritmo propuesto. Las características epidemiológicas coinciden con lo publicado en la literatura. La biología molecular nos permitió diferenciar nítidamente enfermedades que suponíamos emparentadas desde un punto de vista histológico, pero que observando su historia natural, su genética y su respuesta a tratamientos instaurados eran tumores distintos, aunque todos fueran llamados "gliomas". Los estándares internacionales no conciben su diagnóstico sin la biología molecular. No es aceptable que se siga diagnosticando únicamente con estándares histológicos. El algoritmo propuesto podría ser una alternativa viable y confiable.

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