262 The BRAF V600E Mutation and Tumor Cells Are Frequently Seen in Seemingly Normal Brain Parenchyma Beyond Ganglioglioma Tumor Borders: Implications for Seizure and Tumor Control

Abstract

INTRODUCTION: Gangliogliomas are WHO grade I glioneural tumors that are frequently encountered in the work up of medically refractory focal epilepsy. Their management typically involves gross total resection of the MRI-visible tumor. However, seizures may continue to be experienced by the patient post-operatively with no clear explanation. Recent evidence suggested both the unexpected invasive nature of these tumors, as well as an inherent epileptogenic nature of the BRAF-V600 mutation independent of tumor presence. METHODS: We analyzed the peri-lesional tissue resected in epilepsy surgical cases secondary to gangliogliomas in seven patients. RESULTS: Unexpectedly, we identified either satellite tumors within the tissue, or evidence of extension of the BRAF mutation into morphologically normal tissue in four of the five patients with BRAF-V600 positive tumors. No such findings were encountered in the two BRAF-V600 negative cases. CONCLUSIONS: This work highlights the need of extending research efforts into the parenchyma beyond structural lesions in these cases, as our preliminary results suggest a role for field cancerization in these tumors. In addition, these findings have significant implications on the understanding and management of these tumors, which appear to have a poorly described invasive nature. It also provides a potential explanation and treatment target for seizures persisting in patients despite a gross total resection of MRI-visible tumor.