RESUMO
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.
RESUMO
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.
Assuntos
Epilepsia do Lobo Temporal , Hipocampo , Adulto , Humanos , Epilepsia , Epilepsia do Lobo Temporal/diagnóstico , Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Imageamento por Ressonância Magnética , Malformações do Desenvolvimento Cortical/diagnóstico , Malformações do Desenvolvimento Cortical/patologia , Malformações do Desenvolvimento Cortical do Grupo I/diagnóstico , Malformações do Desenvolvimento Cortical do Grupo I/patologiaRESUMO
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.
Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Adulto , Animais , Astrócitos , Sistema Nervoso Central , Humanos , Neuroglia , Adulto JovemRESUMO
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.
Assuntos
COVID-19 , Glioblastoma , Idoso , Brasil/epidemiologia , Glioblastoma/epidemiologia , Glioblastoma/terapia , Humanos , Pandemias , SARS-CoV-2RESUMO
Pilocytic astrocytomas are the primary tumors most frequently found in children and adolescents, accounting for approximately 15.6% of all brain tumors and 5.4% of all gliomas. They are mostly found in infratentorial structures such as the cerebellum and in midline cerebral structures such as the optic nerve, hypothalamus, and brain stem. The present study aimed to list the main characteristics about this tumor, to better understand the diagnosis and treatment of these patients, and was conducted on search of the published studies available in NCBI, PubMed, MEDLINE, Scielo, and Google Scholar. It was possible to define the main histologic findings observed in these cases, such as mitoses, necrosis, and Rosenthal fibers. We described the locations usually most affected by tumor development, and this was associated with the most frequent clinical features. The comparison between the molecular diagnostic methods showed great use of fluorescent in situ hybridization, polymerase chain reaction (PCR), and reverse transcriptase-PCR, important techniques for the detection of BRAF V600E mutation and BRAF-KIAA1549 fusion, characteristic molecular alterations in pilocytic astrocytomas.
Assuntos
Astrocitoma/diagnóstico , Neoplasias Encefálicas/diagnóstico , Hibridização in Situ Fluorescente/métodos , Reação em Cadeia da Polimerase/métodos , Astrocitoma/fisiopatologia , Astrocitoma/terapia , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/terapia , HumanosRESUMO
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.
Assuntos
Fístula Arteriovenosa/cirurgia , Malformações Arteriovenosas Intracranianas/cirurgia , Microcirurgia/métodos , Lesões por Radiação/cirurgia , Radiocirurgia/efeitos adversos , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Pilocytic astrocytoma (PA) is rare in adults comprising 5.1% of the primary central nervous system tumors. The aim is to describe the first Brazilian series of adult patients with PA and compare its features with the available literature. METHODS: We retrospectively review all patients 18 years or older with PA from our institution's database from 1991 to 2018. We analyzed information regarding clinical presentation, location, imaging features, extent of resection, adjuvant treatments, and follow-up. RESULTS: Twenty-three patients with PA were analyzed: 60.9% male; median age 26 years. The most frequent symptoms were headache (34.8%) and seizure (26.1%). Temporal and parietal lobes were the most common locations, 21.7% each. All patients underwent a surgical procedure, gross total resection in 40.9%, subtotal resection in 22.7%, and biopsy in 27.3%. Adjuvant treatment with radiotherapy was performed in 2 patients. Only 4 patients had disease progression, 2 after gross total resection and 2 after subtotal resection. They were all alive and without evidence of new progression at the last follow-up (October 2018). Median overall survival was not reached after a median follow-up time of 88.9 months. CONCLUSIONS: This is the first Brazilian series regarding adults with PA, and our patients had a favorable outcome as reported in recent literature reviews. The tumor's prevalence reduces within older patients and supratentorial lesions are more frequent, especially on the temporal lobe. There was no significant relationship between location and progression, although according to the literature the extent of resection remains the most important prognostic factor.
Assuntos
Astrocitoma/cirurgia , Neoplasias Encefálicas/cirurgia , Adolescente , Adulto , Astrocitoma/complicações , Astrocitoma/epidemiologia , Astrocitoma/radioterapia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/radioterapia , Brasil/epidemiologia , Terapia Combinada , Irradiação Craniana , Progressão da Doença , Feminino , Seguimentos , Cefaleia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia Adjuvante , Estudos Retrospectivos , Convulsões/etiologia , Resultado do Tratamento , Adulto JovemRESUMO
Glioependymal cysts are a rare, congenital, and benign condition. The authors report a case of a 2-year-old female patient who presented with a large exophytic glioependymal cyst located in the left cerebral peduncle, which began with a history of deteriorating function of the left third cranial nerve (CN III). A left 3-piece fronto-orbitozygomatic approach and a microsurgical complete excision of the cyst were performed without complications by accessing the midbrain through the perioculomotor entry zone. The patient's CN III function completely recovered after 3 months. Because there are currently no widely approved and used classification systems for these cysts, their reporting, naming, and classification are quite confusing in the literature. Thus, their origin, classification, and most common locations warrant further investigation. In addition to reporting this case, the authors present their review of the literature.
RESUMO
Medulloblastoma is the most frequent malignant brain tumor in children, representing 20% of all childhood brain tumors. Currently, medulloblastomas are molecularly classified in 4 subgroups that are associated with distinctive clinicopathological features. KBTBD4 mutations were recently described in a subset of MBGRP3 and MBGRP4 medulloblastomas subgroups. However, no other studies reported KBTBD4 mutations in medulloblastomas. Thus, our aim was to investigate KBTBD4 mutations in a Brazilian series of medulloblastoma. We evaluated 128 medulloblastoma patients molecularly classified from 4 Brazilian reference centers. DNA from formalin-fixed, paraffin-embedded samples was screened for KBTBD4 hotspot mutations by Sanger sequencing. Most of the patients were male, average age was 16.5 years old and average overall survival was 55.9 months. The predominant histological subtype was the classic subtype, followed by nodular/desmoplastic, and the predominant medulloblastoma molecular subtype was the MBSHH subgroup (46%), followed by MBGRP3 and MBGRP4 (19%/each), and MBWNT (16%). Among the 128 samples, 111 were successfully sequenced. No KBTBD4 mutations were identified in 111 samples. Our findings suggest that KBTBD4 mutations are uncommon in Brazilian MBGRP3 and MBGRP4 medulloblastomas subgroups. Further studies in a larger series of MBGRP3 and MBGRP4 medulloblastomas are warranted to better assess role of KBTBD4 mutations.
Assuntos
Proteínas de Transporte/genética , Neoplasias Cerebelares/genética , Meduloblastoma/genética , Adolescente , Adulto , Brasil , Neoplasias Cerebelares/mortalidade , Neoplasias Cerebelares/patologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Meduloblastoma/mortalidade , Meduloblastoma/patologia , Pessoa de Meia-Idade , Mutação , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Angiolipomas are benign tumors most commonly found in the thoracic spine. They are composed of mature adipocytes and abnormal vascular elements that usually present with a slowly progressive course of neurological deterioration. CASE DESCRIPTION: A 35-year-old female, with a prior history of back pain, acutely developed paraparesis. When the thoracic magnetic resonance imaging (MRI) revealed a dorsal epidural mass at the T3-T5 level, she underwent a laminectomy for gross total excision of the lesion that proved to be an angiolipoma. On the second postoperative day, the patient was again able to ambulate. CONCLUSION: The angiolipomas of spine are rare causes of spinal cord compression, and those presenting with acute neurological deficits should be immediately treated.
RESUMO
BACKGROUND: Neurofibromas are benign nerve sheath tumors that usually affect peripheral nerves and are related to neurofibromatosis type 1; however, they have not been described as a cause of intraparenchymal brain tumor. CASE DESCRIPTION: We report a case of intracranial myxoid neurofibroma in a 19-year-old female patient manifested as an intense and progressive cephalea, followed by nausea, vomiting, photophobia, and phonophobia. Computed tomography and magnetic resonance imaging showed an extant, expansive left frontoparietal parafalcine/parasagittal tumor. Histopathologic examination determined S-100 protein and CD34 positivity, as well as sparse expression of Ki67 protein, and indicated Schwann cells with characteristic wavy nuclei and intraneural fibroblasts in a myxoid background. Together, these observations characterized the tumor as myxoid neurofibroma. The tumor was excised, and the patient recovered without deficits and with no signs of recurrence after 6 years of follow-up. CONCLUSIONS: This is a novel presentation of a myxoid neurofibroma. The tumorigenesis mechanisms are likely complex and possibly involve the differentiation of Schwann cells present in adrenergic autonomic nerves in the subarachnoid arterial branches or in trigeminal nerves present in the meningeal convexity.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Fibroma/diagnóstico por imagem , Fibroma/patologia , Neoplasias Encefálicas/cirurgia , Diagnóstico Diferencial , Feminino , Fibroma/cirurgia , Humanos , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
Hotspot activating mutations of the telomerase reverse transcriptase (hTERT) promoter region were recently described in several tumor types. These mutations lead to enhanced expression of telomerase, being responsible for telomere maintenance and allowing continuous cell division. Additionally, there are alternative telomere maintenance mechanisms, associated with histone H3 mutations, responsible for disrupting the histone code and affecting the regulation of transcription. Here, we investigated the clinical relevance of these mechanistically related molecules in medulloblastoma. Sixty-nine medulloblastomas, formalin fixed and paraffin embedded, from a cohort of patients aged 1.5-70 years, were used to investigate the hotspot mutations of the hTERT promoter region, i.e. H3F3A and HIST1H3B, using Sanger sequencing. We successfully sequenced hTERT in all 69 medulloblastoma samples and identified a total of 19 mutated cases (27.5%). c.-124:G>A and c.-146:G>A mutations were detected, respectively, in 16 and 3 samples. Similar to previous reports, hTERT mutations were more frequent in older patients (p < 0.0001), being found only in 5 patients <20 years of age. In addition, hTERT-mutated tumors were more frequently recurrent (p = 0.026) and hTERT mutations were significantly enriched in tumors located in the right cerebellar hemisphere (p = 0.039). No mutations were found on the H3F3A or HIST1H3B genes. hTERT promoter mutations are frequent in medulloblastoma and are associated with older patients, prone to recurrence and located in the right cerebellar hemisphere. On the other hand, histone 3 mutations do not seem to be present in medulloblastoma.
Assuntos
Neoplasias Cerebelares/genética , Regulação Neoplásica da Expressão Gênica , Histonas/genética , Meduloblastoma/genética , Mutação , Telomerase/genética , Adolescente , Adulto , Fatores Etários , Idoso , Neoplasias Cerebelares/patologia , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Humanos , Lactente , Masculino , Meduloblastoma/patologia , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Adulto JovemRESUMO
OBJECTIVE: To analyze cases of recurrent glioblastoma subjected to reoperation at a Brazilian public healthcare service. METHODS: A total of 39 patients subjected to reoperation for recurrent glioblastoma at the Department of Neurosurgery, São Paulo Hospital, Federal University of São Paulo, from January 2000 to December 2013 were retrospectively analyzed. RESULTS: The median overall survival was 20 months (95% confidence interval - CI = 14.9-25.2), and the median survival after reoperation was 9.1 months (95%CI: 2.8-15.4). The performance of adjuvant treatment after the first operation was the single factor associated with overall survival on multivariate analysis (relative risk - RR = 0.3; 95%CI = 0.2-0.7); p = 0.005). CONCLUSION: The length of survival of patients subjected to reoperation for glioblastoma at a Brazilian public healthcare service was similar to the length reported in the literature. Reoperation should be considered as a therapeutic option for selected patients.
Assuntos
Neoplasias Encefálicas/mortalidade , Glioblastoma/mortalidade , Recidiva Local de Neoplasia/mortalidade , Reoperação/mortalidade , Adulto , Idoso , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/terapia , Quimiorradioterapia Adjuvante/métodos , Feminino , Glioblastoma/cirurgia , Glioblastoma/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Neoplasia Residual , Reoperação/normas , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Adulto JovemRESUMO
ABSTRACT Objective To analyze cases of recurrent glioblastoma subjected to reoperation at a Brazilian public healthcare service. Methods A total of 39 patients subjected to reoperation for recurrent glioblastoma at the Department of Neurosurgery, São Paulo Hospital, Federal University of São Paulo, from January 2000 to December 2013 were retrospectively analyzed. Results The median overall survival was 20 months (95% confidence interval – CI = 14.9–25.2), and the median survival after reoperation was 9.1 months (95%CI: 2.8–15.4). The performance of adjuvant treatment after the first operation was the single factor associated with overall survival on multivariate analysis (relative risk – RR = 0.3; 95%CI = 0.2–0.7); p = 0.005). Conclusion The length of survival of patients subjected to reoperation for glioblastoma at a Brazilian public healthcare service was similar to the length reported in the literature. Reoperation should be considered as a therapeutic option for selected patients.
RESUMO Objetivo Analisar o papel da reoperação em pacientes com glioblastoma recidivado em um serviço público no Brasil. Métodos Foram analisados retrospectivamente 39 pacientes submetidos à reoperação por recorrência de glioblastoma no Departamento de Neurocirurgia da Universidade Federal de São Paulo, no período de janeiro de 2000 até dezembro de 2013. Resultados A sobrevida global mediana foi de 20 meses (IC 95% = 14.9–25.2), e a sobrevida mediana após a reoperação foi de 9.1 meses (IC 95% = 2.8–15.4). A realização de tratamento adjuvante após a primeira cirurgia foi o único fator associado com a sobrevida global numa análise multivariada (RR = 0.3; IC 95% = 0.2–0.7; p = 0.005). Conclusão A sobrevida dos pacientes submetidos à reoperação em um serviço público no Brasil é semelhante à reportada pela literatura. A reoperação deve ser considerada como uma opção terapêutica em pacientes selecionados.