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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.
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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.
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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
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.
Com a atual pandemia causada pelo coronavírus da síndrome respiratória aguda grave 2 (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, em inglês), foram necessárias medidas de isolamento social que resultaram na interrupção de alguns tratamentos médicos hospitalares. Em relação aos pacientes neuro-oncológicos, principalmente aqueles com distúrbios do sistema nervoso central (SNC), uma interrupção pode causar sérios danos ou até mesmo comprometer o sucesso do tratamento no futuro. Assim, de acordo com a literatura encontrada, é de fundamental importância que cada caso seja avaliado individualmente, para que se decida como prosseguir com o tratamento durante a pandemia, sempre considerando o risco de infecção por SARS-CoV-2 e os benefícios relacionados ao tratamento. São estratégias importantes neste momento a política de não prescrição de medicamentos potencial mente tóxicos, quimioterapia e terapias imunossupressoras, além do uso de técnicas como biópsia estereotáxica e telemedicina.
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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.
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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.
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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.
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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.
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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
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.
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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.
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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.
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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.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Reoperação/mortalidade , Neoplasias Encefálicas/mortalidade , Glioblastoma/mortalidade , Recidiva Local de Neoplasia/mortalidade , Reoperação/normas , Fatores de Tempo , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/terapia , Análise de Sobrevida , Estudos Retrospectivos , Glioblastoma/cirurgia , Glioblastoma/terapia , Neoplasia Residual , Quimiorradioterapia Adjuvante/métodos , Recidiva Local de Neoplasia/cirurgiaRESUMO
AIM: The aim of the present study was to detect the relative expressions of p53, p21(Waf1/Cip1), p27(Kip1) Bcl-2 and cleaved caspase-3 in cervical lesion samples from Brazilian women by immunohistochemistry. MATERIALS AND METHODS: A total of 230 cervical biopsies in paraffin-embedded blocks were studied: 43 were invasive squamous cell carcinomas (SCC), 52 carcinomas in situ/cervical intraepithelial neoplasias III (CIN III), 54 cervical intraepithelial neoplasias II (CIN II), 51 cervical intraepithelial neoplasias I (CIN I) and 30 non-neoplastic lesions (NN) with benign cellular changes. RESULTS: Significant differences were observed in the p53 expression between the different groups: NN and CIN I (p=0.010); NN and CIN II (p<0.00001); CIN II and CIN III (p=0.02); CIN II and CIS (p=0.0220); CIN II and CEC (p=0.010). Regarding p21(WAF1/Cip1), significant differences were observed between NN and CEC (p=0.001); CIN I and CEC (p=0.001); CIN II and CIN III (p=0,001); CIN II and CIS (p=0.0004) and CIN II and CEC (p<0.0001). For p27(Kip1), significant differences were observed between NN and CIN I (p<0.00001); NN and CIN II (p<0.00001); NN and CIS (p=0.038); CIN I and CIN III (p=0.001); CIN I and CIS (p=0.009); CIN I and CEC (p=0.0001); CIN II and CIN III (p=0.0003); CIN II and CIS (p=0.002); CIN II and CEC (p< 0.00001). Bcl-2 and caspase-3 did not show remarkable differences between groups. CONCLUSION: p53, p21(WAF1/CIP1), p27(KIP1) appear to be involved in the course of carcinogenesis. Rare expression of Bcl-2 and cleaved caspase-3 suggests that these proteins probably do not participate in cervical apoptosis.
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Proteínas Reguladoras de Apoptose/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Displasia do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/metabolismo , Brasil , Carcinoma de Células Escamosas/patologia , Caspase 3/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Feminino , Humanos , Técnicas Imunoenzimáticas , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Neoplasias do Colo do Útero/patologia , Displasia do Colo do Útero/patologiaRESUMO
Objective. To evaluate trophoblastic cell proliferation and angiogenesis in tubal pregnancy assessed by immunohistochemical study and their correlation with an average variation of ß -hCG in an interval of 48 hours before surgery. Methods. A prospective study was conducted on 18 patients with a diagnosis of tubal pregnancy. The patients were divided into two groups of ectopic pregnancy of which 11 showed rise of ß -hCG levels and 7 patients showed declining ß -hCG levels in an interval of 48 hours prior to surgery. Trophoblastic cell proliferation and angiogenesis were assessed by Ki-67 and VEGF, respectively. Trophoblastic cell proliferation was assessed by Ki-67 and was classified into three groups (grade I: less than 1/3 of stained nuclei, grade II: 1/3 to 2/3 of the stained nuclei, and grade III: more than 2/3 of the nuclei stained). The cases analyzed for VEGF were divided into three groups (grade I: less than 1/3 of the stained cytoplasm; grade II: 1/3 to 2/3 of the stained cytoplasm; grade III: more than 2/3 of the stained cytoplasm). Statistical analysis was performed using the chi-square, ANOVA, and Kruskal-Wallis tests. Results. The mean variation in the serum ß -hCG levels in 48 hours in tubal pregnancy patients correlated with trophoblastic cell proliferation assessed by Ki-67 and showed a decline of 13.46% in grade I, a rise of 45.99% in grade II, and ascension of 36.68% in grade III (P = 0.030). The average variation in the serum ß -hCG in 48 hours, where angiogenesis was evaluated by VEGF, showed a decline of 18.35% in grade I, a rise of 32.95% in grade II, and ascension of 37.55% in grade III (P = 0.047). Conclusions. Our observations showed a direct correlation of increased levels of serum ß -hCG in 48h period prior to surgery with higher trophoblastic cell proliferation assessed by Ki-67 and angiogenesis assessed by VEGF in tubal pregnancy.
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Heat shock proteins are molecular chaperones that may be constitutively present in cells protecting them from various stresses, such as extreme temperature, anoxia or chemical agents. Cervical cancer is the second most prevalent malignancy of women. In this study, we analyzed the expression of Hsp27 by immunohistochemistry in cervical intraepithelial lesions of Brazilian women, along with samples from non neoplasic lesions (NN). Cervical intraepithelial neoplasia I (CIN I), II (CIN II) and III (CIN III)/in situ carcinoma and squamous cell carcinoma (SCC) were included. Immunostaining was observed in 30 (100%) samples of NN, 46 (92%) in CIN I, 50 (100%) in CIN II, 52 (98.11%) in CIN III/CIS, and 46 (98.11%) in SCC. In group NN Hsp27 immunostaining was heterogeneous, more intense in basal and parabasal layers of the epithelium and less or absent in the intermediate and superficial layer. The majority of the samples of CIS and SCC presented strong staining in allepithelial layers. Metaplasic cells, when present, were strongly stained. In this study, Hsp27 protein was found to be commonly expressed in cervical epithelial cells.