Increased Incidence of Choroid Plexus Carcinoma Due to the Germline TP53 R337H Mutation in Southern Brazil

International audienceBACKGROUND: Choroid plexus carcinomas (CPC) are rare tumors predominantly found in children. Given the high frequency of the germline R337H mutation in the TP53 gene in southern Brazil, we have evaluated the frequency of the R337H mutation in families with CPC in children. METHODOLOGY/PRINCIPAL FINDINGS: The present series included 29 patients that were admitted to the same institution from 1992 to 2010, including 22 children with CPC (0.08-13.6 years of age at diagnosis) and 7 children with papilloma of the choroid plexus (Pp; 0.5-9.8 years of age). Surgical resection was possible in 28 children. Blood and/or tumor DNA was extracted and analyzed using PCR-RFLP and results were confirmed by sequencing 240 bp of the TP53 exon 10. The patients, all parents, and some relatives submitted samples for blood DNA analysis. In addition, we have also examined the presence of the mutation in DNA from paraffin-embedded tumor samples to evaluate loss of heterozygosity. We found 63.3% (14/22) of the CPC patients positive for the germline R337H mutation; CPC samples were either heterozygous (n = 7), lost only the wild-type (n = 4), or only the R337H copy (n = 2). One CPC sample was not available. All Pp cases (7/7, 100%) were negative for R337H. Cure (>5 years survival free of disease) was observed in 18.1% of the CPC cases with the R337H mutation (2/11), 71.4% of the Pp (5/7), and 25% of CPC cases negative for the R337H mutation (2/8). Family history of cancer (with 2 or more cancer cases) was exclusively identified on the parental side segregating the R337H mutation, and 50% (7/14) of them were compatible with Li-Fraumeni-like syndrome. SIGNIFICANCE: Our results show for the first time that the R337H TP53 mutation is responsible for 63% of the CPC cases in children, suggesting a higher incidence of CPC in southern Brazil

Glioblastoma pediátrico: estudo clínico patológico de 12 casos com imunoistoquímica para proteína p53 Pediatric glioblastoma: a clinicopathological study of 12 cases with p53 protein immunohistochemistry

Glioblastoma é um dos tumores primários mais letais do sistema nervoso central (SNC). Apesar dos significativos progressos, há poucas análises em crianças. Com o objetivo de avaliar localização, idade, sexo, sobrevida e imunoistoquímica para proteína p53, foram coletados casos de glioblastomas pediátricos do "Banco de Tumores do SNC de Curitiba", durante 1987-2003 e do Hospital Municipal Jesus, Rio de Janeiro, de 1970 a 1988. Doze preencheram os critérios de inclusão. A idade variou até 12 anos (média 7), sendo sete do sexo feminino e cinco do masculino. A sobrevida média foi 7,9 meses. Localizavam-se em hemisférios cerebrais (58,4%), mesencéfalo e tronco (33,3%) e um no cerebelo. A imunoistoquímica demonstrou p53 positivo em 9 (75%). Em conclusão, glioblastoma tem comportamento semelhante entre crianças e adultos, sendo nestas menos freqüentes. Acomete hemisférios cerebrais com maior freqüência que estruturas infratentoriais, mostrando alta sensitividade com a imunomarcação para proteína p53, sendo nestes casos mais agressivos, com menor sobrevida.<br>Glioblastoma is one of the most lethal central nervous system (CNS) primary tumor. Although significant progress, only few analysis have been made in pediatric glioblastoma, which are less common and have worse prognosis than in adults. To evaluate gender, site, age, survival, and immunohistochemistry to p53, we selected cases of pediatric glioblastoma of "CNS Tumors Database in Curitiba", 1987-2003 and of the Hospital Municipal Jesus, Rio de Janeiro, 1970-1988. Twelve tumors were included. The age ranged from up to 12 years (median 7). There were 7 females and 5 males. The median survival was 7.9 months. Location was: cerebral hemispheres (58.4%), mesencephalon and brainstem (33.3%) and one case in the cerebellum. Immunostained to p53 in 9 (75%) cases. In conclusion, glioblastoma behaves similarly in children and adults. It is rare in children, affects both cerebral hemispheres more than brainstem and cerebellum and shows strong immunohistochemistry to p53

Neurological complications of hematopoietic stem cell transplantation (HSCT): a retrospective study in a HSCT center in Brazil Complicações neurológicas do transplante de células tronco hematopoiéticas (TCTH): estudo retrospectivo em um centro de TCTH no Brasil

We present the neurological complications evaluated in a series of 1000 patients who underwent hematopoietic stem cell transplantation (HSCT). Central nervous system (CNS) neurological complications, particularly brain hemorrhages, were the most common, followed by seizures and CNS infections. An unusual neurological complication was Wernicke's encephalopathy. Less frequent neurological complications were metabolic encephalopathy, neuroleptic malignant syndrome, reversible posterior leukoencephalopathy syndrome, brain infarct and movement disorders. The most common neurological complication of the peripheral nervous system was herpes zoster radiculopathy, while peripheral neuropathies, inflammatory myopathy and myotonia were very rarely found.<br>Apresentamos as complicações neurológicas avaliadas em uma série de 1000 pacientes submetidos ao transplante de células tronco hematopoiéticas (TCTH). As complicações neurológicas do sistema nervoso central foram as mais encontradas, particularmente as hemorragias encefálicas, seguidas por crises convulsivas e por infecções. Uma complicação peculiar foi a encefalopatia de Wernicke. Menos freqüentemente foram encontrados casos de encefalopatia metabólica, síndrome maligna neuroléptica, leucoencefalopatia posterior reversível, infarto cerebral e os distúrbios do movimento. Entre as complicações neurológicas do sistema nervoso periférico a mais encontrada foi a radiculopatia pelo herpes zoster, enquanto que raramente se observaram casos de polineuropatias periféricas, miopatia inflamatória e de miotonia