NGTS-02CHARACTERISTICS OF GLIOMAS IN PATIENTS WITH ENCHONDROMATOSIS

Abstract

BACKGROUND: Enchondromatosis (Ollier disease and Maffucci syndrome) are rare non-hereditary skeletal disorders which were recently shown to be due to somatic mosaic mutations of IDH1 or IDH2. Enchondromatosis patients are at increased risk of developing gliomas. The aim of the present study was to describe the characteristics of gliomas occurring in these patients in comparison to the characteristics of sporadic IDH mutated gliomas. METHODS: The clinical, histological and radiological characteristics of 39 enchondromatosis patients with gliomas (present series n = 7, previously reported cases n = 32) were analyzed and compared to the characteristics of 159 patients with sporadic IDH mutated gliomas. RESULTS: Gliomas occurring in patients with enchondromatosis were diffuse low-grade (73%) or anaplastic gliomas (21%). They were, most frequently located in the frontal lobe (53%) or in the brainstem (23%). An IDH mutation was present in 7 out of the 8 patients in whom it was assessed. Median age at diagnosis was 28 years [range 6-46]. Twelve patients (30.8%) had multicentric gliomas and 2 patients a gliomatosis cerebri. Compared to sporadic IDH mutated gliomas, enchondromatosis gliomas were diagnosed at an earlier age (28 versus 44 years, p < 0.001), were more frequently multicentric (30.8% versus 1.3%, p < 0.001) and were more frequently located within the brainstem (22.5% versus 0.6%, p < 0.001). CONCLUSION: The histological and molecular characteristics of gliomas observed in patients with enchondromatosis as well as their high rate of multicentricity are in agreement with the hypothesis of an underlying mosaicism of the IDH mutation. The differences between the characteristics of enchondromatosis and sporadic IDH mutated gliomas (earlier age at diagnosis, more frequent brainstem involvement) suggest that the characteristics of IDH related gliomagenesis could vary according to the age at which the mutation is acquired.