Clinical, demographic, anatomopathological, and molecular findings in patients with medulloblastoma treated in a single health facility / Achados clínicos, demográficos, anatomopatológicos e moleculares de portadores de meduloblastoma tratados em uma única instituição

ABSTRACT Objective: To describe the clinical, demographic, anatomopathological, molecular, and survival characteristics of patients with medulloblastoma. Methods: Retrospective study based on patient information obtained from the review of medical records. Overall and event-free survival were analyzed using the Kaplan-Meier estimator, and the curves were compared by the log-rank test. Results: Among the patients investigated, 70 were male (66%), and age at diagnosis ranged from 2 months to 22 years. The most frequent signs and symptoms were headache (80.8%) and vomiting (75.8%). Regarding treatment, most patients (63.2%) underwent complete surgical resection, with a predominance of classic histology (63.2%). The 5-year overall survival rate was 67.9%, and the 10-year rate was 64.2%. Patients with molecular profile characteristic of the wingless (WNT) subgroup had a better prognosis, with 5-year overall survival of 75%. Conclusions: The clinical, demographic, anatomopathological, and molecular characteristics of patients with medulloblastoma described in the present study were mostly similar to those reported in the literature. Patients submitted to complete tumor resection had better clinical outcomes than those who underwent incomplete resection/biopsy. Patients classified as high-risk showed worse overall and event-free survival than those in the standard-risk group, and the presence of metastasis at diagnosis was associated with recurrence.

RESUMO Objetivo: Descrever as características clínicas, demográficas, anatomopatológicas, moleculares e de sobrevida de pacientes portadores de meduloblastoma. Métodos: Estudo retrospectivo, no qual as informações dos pacientes foram obtidas pela revisão dos prontuários médicos. Análises de sobrevida global e de sobrevida livre de eventos foram realizadas por meio da construção de curvas de Kaplan-Meier e a comparação entre as curvas foi feita pelo teste log-rank. Resultados: Entre os pacientes analisados, 70 pertenciam ao sexo masculino (66%) e a idade ao diagnóstico variou de dois meses a 22 anos. Os sinais e sintomas de maior frequência foram cefaleia (80,8%) e vômitos (75,8%). Em relação ao tratamento, a maioria (63,2%) dos pacientes foi submetida à ressecção cirúrgica total e apresentava como histologia predominante a forma clássica (63,2%). A taxa de sobrevida global em cinco anos foi de 67,9% e, em 10 anos, de 64,2%. Os pacientes com perfil molecular característico do subgrupo wingless (WNT) apresentaram melhor prognóstico, com sobrevida global em cinco anos de 75%. Conclusões: As características clínicas, demográficas, anatomopatológicas e moleculares dos pacientes com meduloblastoma descritas no presente estudo foram majoritariamente semelhantes às descritas na literatura. Pacientes submetidos à ressecção completa do tumor tiveram melhor evolução clínica do que aqueles com ressecção incompleta/biópsia. Pacientes estratificados como de alto risco apresentaram pior sobrevida global e livre de eventos do que o grupo standard e a presença de metástases ao diagnóstico se mostrou associada à ocorrência de recidiva da doença.

Risk factors for the prognosis of pediatric medulloblastoma: a retrospective analysis of 40 cases

OBJECTIVES: In this study, we evaluated the association of molecular subtypes, clinical characteristics and pathological types with the prognosis of patients with medulloblastoma. METHODS: We analyzed forty patients with medulloblastoma who underwent surgical resection at our center between January 2004 and June 2014. Risk factors associated with survival, disease progression and recurrence were analyzed with a univariate Cox regression analysis, and the identified significant risk factors were further analyzed by Kaplan-Meier survival curves. RESULTS: Factors associated with overall survival included M stage (p=0.014), calcification (p=0.012), postoperative treatment, postoperative Karnofsky Performance Scale (KPS) score (p=0.015), and molecular subtype (p=0.005 for WNT and p=0.008 for SHH). Number of symptoms (p=0.029), M stage (p<0.001), and postoperative radiotherapy (p=0.033) were associated with disease progression. Patients with the WNT or SHH subtype had better survival outcomes than patients with non-WNT/SHH subtypes. Risk factors for disease progression-free survival were symptoms >2 and ≥M1 stage without postoperative radiotherapy. The risk of recurrence increased with advanced M stage. Protective factors for recurrence included M0 stage and a combination of chemotherapy and radiotherapy. CONCLUSION: We identified the risk factors associated with survival, disease progression and recurrence of medulloblastoma patients. This information is helpful for understanding the prognostic factors related to medulloblastoma.

Mortalidad por tumores cerebrales malignos durante los primeros 30 días de la cirugía / Mortality from malignant brain tumors within the first 30 days after surgery

Introducción: las complicaciones neurológicas en la cirugía de los gliomas de alto grado están relacionadas con problemas en localización y exposición, extensión de la resección y la manera en que se manipulan los tejidos. Hay factores secundarios que contribuyen a la evolución desfavorable y la muerte precoz de un paciente. Objetivos: establecer la relación que existe entre la mortalidad en los primeros 30 días y diferentes factores de riesgo e identificar causas de muerte. Métodos: fueron operados 131 pacientes en el Servicio de nNeurocirugía del Hospital Calixto García desde enero de 2005 a enero de 2010, con el diagnóstico de gliomas de alto grado. De ellos, 14 fallecieron en los primeros 30 días. Variables principales utilizadas: edad, localización tumoral, grado de resección quirúrgica y causas de la muerte. Se aplicó la prueba chi cuadrado de independencia con un nivel de significación de 0,05 para evaluar relación entre variables. Resultados: la mortalidad perioperatoria fue del 10,7 por ciento. El riesgo fue mayor en el sexo masculino; discretamente mayor en los mayores de 60 años. No estuvo relacionado con la localización del tumor. Operar con signos de enclavamiento cerebral, incrementó al máximo la probabilidad de fallecer en el primer mes. La resección parcial en relación con la total y con la biopsia mostró mayor probabilidad de mortalidad. No hubo muerte transoperatoria. Conclusiones: los factores que influyeron principalmente en la evolución desfavorable fueron: la baja puntuación en la escala de Karnofskyy una resección limitada, igual o menor que 50 por ciento en una craneotomía(AU)

Introduction: The neurological complications found in the high gradegliomas surgery are primarily related with location, exposure and extension of the resection and with the way of handling tissues. There are secondary factors that contribute to the unfavorable progression and even the early death of patients that suffers this disease. Objectives: To set the relationship between mortality within the first 30 days after surgery and the different risk factors, and to identify the causes of death. Methods: One hundred and thirty one patients diagnosed with high gradegliomas were operated on in the neurosurgery service of Calixto García hospital from January 2005 through January 2010. Fourteen of them died within the first thirty days. The study variables were age, tumor location, degree of surgical resection and causes of death. Chi-square test of independence with significance level of 0.05 was applied to evaluate the association among the variables. Results: The perioperative mortality rate was 10.7 percent. The risk of death was higher in males; slightly higher in those over 60 years and unrelated to the tumor location. If patients are operated on with signs of brain herniation, they are more likely to die in the first month. Partial compared to total resection and to biopsy showed higher mortality probabilities. There was no intraoperative death. Conclusions: The low scoring in the Karnofsky Scale, and a partial resection equal or smaller than 50 percent in a craniotomy were the influential factors in an unfavorable outcome of disease(AU)

Immunohistochemical expression of markers Ki-67, neun, synaptophysin, p53 and HER2 in medulloblastoma and its correlation with clinicopathological parameters / Expressão imunoistoquímica dos marcadores Ki-67, neun, sinaptofisina, p53 e HER2 em meduloblastoma e sua correlação com os parâmetros clínico-patológicos

Medulloblastoma (MB) is the most common malignant brain tumor in childhood. The alterations found include: presence of oncoproteins p53 and HER2, elevated mitotic index, and presence of neuronal differentiation. The aim of this study was to determine the immunohistochemical expression of markers Ki-67, NeuN, synaptophysin, HER2 and p53 in 40 MB samples and their correlation with clinicopathologic parameters and survival. In 29 patients (72.5 percent), >20 percent of cells were positive for Ki-67. Males showed greater ki-67 expression (p=0.02) and smaller survival rates (p=0.002). NeuN and synaptophysin were negative in 16 (40 percent) and 8 (20 percent) cases, respectively. P53 was positive in 18 (45 percent) cases, with 11 (61 percent) weakly positive and 7 (39 percent) strongly positive. HER2 was positive in 23 (57.5 percent) of the samples and did not show statistical association with survival (p=0.07).

Meduloblastoma (MB) é o tumor maligno encefálico mais freqüente na infância. dentre as alterações encontradas estão: a presença das oncoproteínas p53 e HER2, elevado índice mitótico e presença de diferenciação neuronal. o objetivo deste estudo foi determinar a expressão imunoistoquímica (IMQ) dos marcadores Ki-67, NeuN, sinaptofisina, HER2 e p53 em 40 amostras de MB, correlacionando-as com parâmetros clinicopatológicos e com a sobrevida. Vinte e nove pacientes (72,5 por cento) apresentaram 20 por cento ou mais das células positivas para Ki-67. os pacientes do sexo masculino apresentaram maior expressão do Ki-67 (p=0,02) e também menor sobrevida (p=0,002). NeuN e sinaptofisina foram negativos em 16 (40 por cento) e 8 (20 por cento) casos, respectivamente. P53 foi positivo em 18 (45 por cento) casos, sendo 11 (61 por cento) fracamente positivos e 7 (39 por cento) fortemente positivos. HER2 foi positivo em 23 (57,5 por cento) das amostras e não demonstrou associação estatística com a sobrevida (p=0.07).

Medulloblastomas: clinical profile, treatment techniques and outcome - an institutional experience.

The present series reports an audit on the patterns of presentation, radiation treatment techniques, failure pattern and outcome in the 36 patients treated at a single institution. Patients were accrued between October 1991 and September 1999. They underwent total or subtotal resection along with craniospinal irradiation. The dose to the cranium ranged from 30 to 43Gy (median- 36Gy), to the spine from 20 - 36Gy (median- 36Gy) and the posterior fossa boost, which was delivered in 32 cases, ranged from 14 to 24Gy (median -18Gy). Simulator film evaluation was carried out at the time of analysis based on the French Medulloblastoma Group guidelines, which revealed a significant under-dosage in the region of posterior fossa and cribriform plate in 27% and 19% respectively. Adjuvant chemotherapy was administered in 7 patients. Salvage treatment in the form of chemotherapy (5 cases) and re-irradiation (2 cases) were attempted but were ineffective. The overall survival (OS) and progression free survival (PFS) rates were 54% and 40% respectively, with the median being 75 and 29 months respectively. Amongst all the prognostic factors considered, on univariate analysis, duration of symptoms was significant for PFS with a trend towards significance for OS, while extent of debulking had a trend towards significance for PFS. No factor emerged significant on multivariate analysis.

Análise e fatores prognósticos do meduloblastoma e sua forma desmoplásica / Analysis and prognostic factors of the medulloblastomas and desmoplasic medulloblastomas

O Meduloblastoma cerebelar, tumor neuroectodérmico primitivo do sistema nervoso central, tem origem no véu medular posterior medial do vermis cerebelar ou, nos casos laterais, na camada granular externa de Obersteimer dos hemisférios cerebelosos. É caracterizado por grande controvérsia na literatura. Dentre suas variantes morfológicas, verifica-se o meduloblastoma desmoplásico, descrito por Rubinstein, em substituiçao ao sarcoma aracnóideo cerebelar de Forster & Gagel, de topografia predominantemente hemisférica, consistência fibrótica, padrao histológico rico em reticulina, incidência maior no adulto, e menor agressividade oncobiológica. Um tipo destes tumores, com melhor prognóstico, é o meduloblastoma desmoplásico do adulto, de topografia lateral, com evoluçao pré-operatória mais longa. A radioterapia de todo neuroeixo, com dose maior ou igual a 5500 rads na fossa posterior participa como fator importante de melhor prognóstico nestes tumores. Recentemente, a quimioterapia vem oferecendo melhores resultados como tratamento adjuvante associado pré ou pós-radioterapia no meduloblastoma. Finalmente, depreende-se dos dados retirados da literatura pela similitude entre o meduloblastoma clássico e o desmoplásico, em relaçao ao quadro clínico e natureza histológica, destacando a maior sobrevida aos 2 e 5 anos neste último, nao justificando tratamento diferenciado em relaçao ao primeiro.

Tumores da regiao do angulo ponto-cerebelar. Uma observacao de 50 casos / Cerebellopontine angle tumors: a review of 50 cases

Tumores da regiao do angulo ponto-cerebelar (APC) sao relativamente comuns e, embora histologicamente sejam em sua grande maioria benignos, ainda hoje representam um desafio no seu diagnostico e tratamento. No presente trabalho os autores apresentam 50 casos de tumores de APC operados e anatomopatologicamente comprovados. Os neurinomas do acustico (NA) corresponderam a 78% , os meningeomas a 10% e outros tumores (2 meduloblastomas, 1 neurinoma do trigemio, 1 neurofibroma bilateral do acustico, 1 hemangioblastoma e 1 metastase de melanoma ). Os sintomas mais comuns foram: lesao VIII nervo craniano (88% ), sinais de hipertensao intracraniana(68% ) e disturbios cerebelares(38% ). Os tumores foram, em sua grande maioria(74% ), diagnosticados quando ja com mais do que 2,5 cm de diametro, com compressao do neuro-eixo, de nervos cranianos e hidrocefalia associada na maior parte dos casos. As fistulas liquoricas e as infeccoes foram as complicacoes mais comuns, embora todas tenham sido curadas. A evolucao pos-operatoria esteve diretamente relacionada com o quadro neurologico pre-operatorio e com o tamanho do tumor, o que reforca a necessidade do diagnostico precoce destas lesoes. A mortalidade observada foi de 14% , basicamente nos tumores malignos ou nos benignos de grandes dimensoes