RARE-26. MUTATIONS IN MAPK PATHWAY GENES ARE CHARACTERISTIC AND CONFIRMATORY OF MULTINODULAR AND VACUOLATING NEURONAL TUMOR OF THE CEREBRUM

BACKGROUND: Multinodular and vacuolating neuronal tumor of the cerebrum (MVNT) is a rare, recently described neoplasm in the 2016 World Health Organization (WHO) classification with 14 cases reported to date. MVNTs usually present with epilepsy or are discovered incidentally. Median age of diagnosis is 44.9 years (22 to 71 years), and the most common location is the temporal lobe (∼65%). METHODS/RESULTS: After reviewing 282 patients enrolled in our natural history study between September 2016 and August 2017, we uncovered two additional cases: the first patient is a 39-year-old woman and the other is a 57-year-old man. The tumors were localized in the left temporal and left frontal lobes respectively. Gross total resection was performed in both cases. Histological features were consistent with the 2016 WHO classification and other published reports. A CNS specific molecular panel revealed a BRAF p.Leu597Arg missense mutation in our first patient, a mutation that was recently reported in one other MVNT but has not been detected in any other primary CNS neoplasm within our database. The second patients lesion was found to have MAP2K1 p.Gln56Pro missense mutation. Our literature review found 2 cases with BRAF and 5 cases with MAP2K1 mutations in MVNT. MAPK pathway alterations reported in other glioneuronal tumors include BRAF p.Val600Glu mutations as well as BRAF fusions, neither of which have been reported in MVNTs to date. CONCLUSIONS: MVNT while rare, will likely be increasingly recognized. Our results suggest that the BRAF p.Leu597Arg missense mutation, (now described in two cases) and the MAP2K1 p. Gln56Pro missense mutation, may be useful diagnostic adjuncts to histopathological features and in differentiating this entity from more commonly epilepsy associated glioneuronal tumors.