Whole-body magnetic resonance imaging of Li-Fraumeni syndrome patients: observations from a two rounds screening of Brazilian patients

Daniele Paixão,Amanda França Nóbrega,Maria Isabel Achatz,Kelvin César De Andrade,Marcos Duarte Guimarães,Rubens Chojniak

doi:10.1186/s40644-018-0162-8

Abstract

BackgroundLi-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.MethodsOver 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.ResultsA 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.ConclusionsWB-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.

Highlights

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
For individuals with LFS, there is sufficient evidence to indicate that the benefits of screening outweighs its risks. Considering this unique population that has a high frequency of LFS patients, the aim of this study was to evaluate the use of whole-body magnetic resonance imaging (WB-MRI) for early tumor detection in Brazilian LFS patients
We evaluated if there was indication of unnecessary invasive procedures in patients with positive results, i.e., biopsy or surgery performed with unconfirmed histopathological result of cancer

Summary

Introduction

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. Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome that is associated with germline TP53 mutations [1]. Those affected by this syndrome are at high risk of developing multiple tumors, both as children and as young adults. The spectrum of tumors that characterize LFS include premenopausal breast cancer, In Brazil, there is a high prevalence of LFS due to a founder effect [10]. Effective screening strategies for LFS patients represent a major challenge due to the wide spectrum of tumors and their variable ages at onset that characterize this syndrome. Since impaired p53 function may enhance the risk of radiation-induced primary tumors in these subjects, the use of this and other radiation-based imaging modalities is not recommended [16,17,18]

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