RESUMO
Up to 20% of patients with pilocytic astrocytoma (PA) experience a poor outcome. BRAF alterations and Fibroblast growth factor receptor 1 (FGFR1) point mutations are key molecular alterations in Pas, but their clinical implications are not established. We aimed to determine the frequency and prognostic role of these alterations in a cohort of 69 patients with PAs. We assessed KIAA1549:BRAF fusion by fluorescence in situ hybridization and BRAF (exon 15) mutations by capillary sequencing. In addition, FGFR1 expression was analyzed using immunohistochemistry, and this was compared with gene amplification and hotspot mutations (exons 12 and 14) assessed by fluorescence in situ hybridization and capillary sequencing. KIAA1549:BRAF fusion was identified in almost 60% of cases. Two tumors harbored mutated BRAF. Despite high FGFR1 expression overall, no cases had FGFR1 amplifications. Three cases harbored a FGFR1 p.K656E point mutation. No correlation was observed between BRAF and FGFR1 alterations. The cases were predominantly pediatric (87%), and no statistical differences were observed in molecular alterations-related patient ages. In summary, we confirmed the high frequency of KIAA1549:BRAF fusion in PAs and its association with a better outcome. Oncogenic mutations of FGFR1, although rare, occurred in a subset of patients with worse outcome. These molecular alterations may constitute alternative targets for novel clinical approaches, when radical surgical resection is unachievable.
Assuntos
Astrocitoma/diagnóstico , Astrocitoma/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Adolescente , Adulto , Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Adulto JovemRESUMO
É relatado o caso clinico de paciente adulta, do sexo feminino, há 18 meses com lesões cutâneas nodulares, disseminadas, sem alterações da sensibilidade, com hepatesplenomegalia febril há seis meses. Diagnosticada hanseníase com evolução semelhante à da tuberculose miliar crônica. Foi necessário o tratamento preconizado pela Organização Mundial de Saúde (OMS) para portadores da forma multibacilar, com posterior acréscimo de medicamentos para resolução de quadro reacional. Esta descrição alerta para a não detecção precoce da doença, existência de contágio não identificável e para o risco decorrente da imensa contaminação e disseminação incontrolável da infecção.
This article shows the exotic evolution of leprosy with unknown fever origin, hepatosplenolinfadenopaty and subcutaneous nodules. Brazil is a top priority country for leprosy control since it represents between 80% and 90% of the total burden leprosy in the American continent. Therefore, special and intensified efforts are required to eradicate the disease by the active involvement of municipalities joining efforts to early diagnosis and adequat therapy.