BRAF V600E mutations in glioneuronal tumours in epilepsy

Introduction: Long-term epilepsy-associated tumours (LEATs) are typically low grade and often glioneuronal in nature. Controversial and newer entities not included in the current WHO classification include the diffuse DNT and nodular vacuolated neuronal tumour (VNT). The differential diagnosis of LEATs ranges from diffuse gliomas to malformations. Point mutations of the BRAF gene (V600E mutations) have been shown in a range of glioneuronal tumours, such as PXA, gangliogliomas, desmoplastic infantile gliomas as a diagnostically useful test. We investigated BRAF mutations in a range of LEATs including these newer and controversial entities.Material and methods: We included 38 cases; 15 diffuse DNT, 5 VNT, 7 gangliogliomas, 8 complex DNT and 3 FCD type IIB cases. All of the patients have given consent for research and the project has ethical approval. In each case sections were taken of the tumour, the more cellular areas micro-dissected and sequencing for BRAF mutation carried out in addition to immunostaning for BRAF mutation. The findings were correlated with clinical and pathological features. Results: There were no mutations detected in the typical DNT, VNT or FCD IIB group but they were identified in 28% of the diffuse DNT group and 33% of GG group. All BRAF mutated cases were in the temporal lobe and all tumours were CD34 positive. All cases with confirmed BRAF mutations were positive with BRAF immunohistochemistry, with patchy labeling of glial in addition to neuronal elements. Positive immunolabeling was also seen in a few cases negative for the V600E mutation. Conclusion: In this small series the incidence of confirmed BRAF mutation in ganglioglioma and diffuse DNT was similar which could support that these entities are related. Immunohistochemistry for BRAF mutation may prove a specific and a more sensitive method of detection in these tumours which comprise mixed tumour and normal cell populations.