RESUMEN
BACKGROUND: Li-Fraumeni syndrome (LFS) is an autosomal dominant disease that is associated with germline TP53 mutations and it predisposes affected individuals to a high risk of developing multiple tumors. In Brazil, LFS is characterized by a different pattern of TP53 variants, with the founder TP53 p.R337H mutation being predominant. The adoption of screening strategies to diagnose LFS in its early stages is a major challenge due to the diverse spectrum of tumors that LFS patients can develop. The purpose of this study was to evaluate two rounds of whole-body magnetic resonance imaging (WB-MRI) which were conducted as a screening strategy for LFS patients. METHODS: Over a 4-year period, 59 LFS patients underwent two rounds of WB-MRI. Each MRI was characterized as positive or negative, and positive cases were further investigated to establish a diagnosis. The parameters used to evaluate the WB-MRI results included: positive rate, number of invasive investigations of positive results, and cancer detection rate. RESULTS: A total of 118 WB-MRI scans were performed. Positive results were associated with 11 patients (9.3%). Seven of these patients (11.8%) were identified in the first round of screening and 4 patients (6.7%) were identified in the second round of screening. Biopsies were performed in three cases (2.5%), two (3.4%) after the first round of screening and one (1.7%) after the second round of screening. The histopathological results confirmed a diagnosis of cancer for all three cases. There was no indication of unnecessary invasive procedures. CONCLUSIONS: WB-MRI screening of LFS carriers diagnosed cancers in their early stages. When needed, positive results were further examined with non-invasive imaging techniques. False positive results were less frequent after the first round of WB-MRI screening.
Asunto(s)
Síndrome de Li-Fraumeni/diagnóstico por imagen , Imagen por Resonancia Magnética , Imagen de Cuerpo Entero , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Introdução: A Síndrome de Li-Fraumeni (LFS) é uma síndrome autossômica dominante rara, relacionada a mutações germinativas no gene TP53, que predispõe a um alto risco de desenvolver múltiplos tumores em idade jovem, incluindo câncer de mama na pré-menopausa, sarcomas, carcinoma adrenocortical e tumores cerebrais. A adoção de estratégias de rastreamento para o diagnóstico precoce de tumores em portadores da LFS constitui um grande desafio devido ao amplo espectro tumoral. A ressonância nuclear magnética rápida de corpo inteiro (RMCI) tem sido indicada como exame de rastreamento na detecção de tumores, principalmente sarcomas, em portadores. No Brasil, a LFS apresenta um padrão de mutação diferente de outros lugares do mundo, com predomínio da mutação p.R337H em TP53, devido à ocorrência de um efeito fundador, com prevalência de 0,21-0,27% na população do Sul e Sudeste do país. Objetivo: O objetivo deste estudo é avaliar a utilização da RMCI como estratégia de rastreamento na detecção de tumores em portadores da LFS. Pacientes e Métodos: Um total de 96 RMCI foram realizadas em 61 portadores de mutações germinativas no gene TP53. Destes, 51 pacientes (51/61-83%) eram portadores da mutação p.R337H. Os exames foram realizados no período de 28 meses, sendo que 35 pacientes foram submetidos a duas RMCI com intervalo mínimo de 12 meses. Resultados: Do total de 96 RMCI realizadas, obtivemos uma taxa de positividade de 8,5%. Investigações adicionais com exames de imagem foram realizadas em todas as RMCI positivas para definição do diagnóstico. Foi necessária investigação invasiva com biópsia em dois casos (2%) nos quais exames anatomopatológicos confirmaram os diagnósticos de lesões malignas, sendo um carcinoma de células renais e um condrossarcoma grau 1. Não houve indicação de procedimentos invasivos desnecessários. Ambas lesões malignas diagnosticadas foram detectadas em indivíduos assintomáticos na primeira RMCI a que foram submetidos e em estádio inicial, sendo tratadas com ressecção cirúrgica. Não foram necessários tratamentos adjuvantes de quimioterapia ou radioterapia. A RMCI apresentou alta taxa de sucesso em sua execução (97%) com baixa necessidade de sedação (3%), boa tolerância e aceitação. Conclusão: Os resultados deste estudo mostraram que o rastreamento baseado em RMCI é possível na maior parte dos portadores da LFS, permitindo a detecção de neoplasias malignas precocemente e com baixas taxas de reconvocação e de investigações invasivas. Assim, a RMCI pode ser uma importante ferramenta para detecção de tumores em pacientes portadores da LFS.
Introduction: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant syndrome related to germline mutations in the TP53 gene. It predisposes to a high risk of developing multiple tumors at a young age, including breast cancer in pre-menopausal, sarcomas, carcinoma adrenocortical and brain tumors. The adoption of screening strategies for early diagnosis of tumors in LFS of carriers is a major challenge due to the diverse spectrum of tumors. The rapid whole-body magnetic resonance (RWB-MRI) has been indicated as a screening strategy of tumours for this patients, especially sarcomas. In Brazil, the LFS shows a different pattern of mutation elsewhere in the world, with predominance of p.R337H TP53 mutation, due to the occurrence of a founder effect, with prevalence of 0.21-0.27% in south/southeast of the country. Objective: The aim of this study is to evaluate the use of RWB-MRI as a screening strategy for tumor detection in patients with LFS. Patients and Methods: A total of 96 RWB-MRI were performed in 61 carriers of germline mutations in the TP53 gene. Of these, 51 patients (51/61-83%) carried the Brazilian founder mutation p.R337H. The RWB-MRI were performed in the period of 28 months, and 35 patients underwent two RWBMRI with a minimum interval of 12 months. Results: A total of 96 RWB-MRI were performed with a positivity rate of 8.5%. Further investigation with imaging exams were performed in all the positive RWB-MRI to define the diagnosis.It required invasive investigation with biopsy in two cases (2%) in which histopathological results confirmed the diagnosis of malignancy, including one renal cell carcinoma and grade 1 chondrosarcoma. There was no indication of unnecessary invasive procedures. Both lesions were detected in asymptomatic individuals in the first RWB-MRI and at an early stage, being treated with surgical resection. Adjuvant chemotherapy or radiation treatments were not necessary. RWB-MRI had a high success rate in its execution (97%) with low need for sedation (3%), good tolerance and acceptance. Conclusion: The results of this study showed that screening based on RWB-MRI is possible in most patients with LFS, enabling early detection of malignant tumors and with lower recall rates and invasive investigations. Thus, RWB-MRI can be an important tool for the detection of cancer in patients with LFS.