Systematic review and cumulative analysis of clinical properties of BRAF V600E mutations in PLNTY histological samples

Purpose Polymorphous low-grade neuroepithelial tumors of the young (PLNTY) represent a rare pediatric-type tumor that most commonly presents as medically refractory epilepsy. PLNTY has only recently been recognized as a distinct clinical entity, having been first described in 2016 and added to the World Health Organization classification of CNS tumors in 2021. Molecular studies have determined that PLNTY is uniformly driven by aberrant MAPK pathway activation, with most tumors carrying either a BRAF V600E mutation or activating FGFR2 or FGFR3 fusion protein. Although it is known that these driver mutations are mutually exclusive, little is known about differences in clinical presentation or treatment outcomes between PLNTY cases driven by these distinct mutations. Methods We performed a systematic review and cumulative analysis of PLNTY cases to assess whether or not PLNTY tumors carrying the BRAF V600E mutation exhibit different clinical behaviors. By searching the literature for all cases of PLNTY wherein BRAF V600E status was characterized, we compiled a dataset of 62 unique patient instances. Using a logistic regression-based approach, we assessed a primary outcome of what factors of a clinical presentation were associated with BRAF V600E mutations and a secondary outcome of what factors predicted total seizure freedom post-surgical resection. Results PLNTY cases carrying BRAF V600E mutations in the literature were strongly positively associated with adult patients ( p = 0.0055, OR = 6.556; 95% Conf. Int. = 1.737–24.742). BRAF V600E status was also positively associated with tumor involvement of the temporal lobe ( p = 0.0046, OR = 11.036; 95% Conf. Int. = 2.100–58.006). Male sex was also positively associated with BRAF V600E status, but the result did not quite achieve statistical significance ( p = 0.0731). BRAF V600E status was not found to be associated with post-operative seizure freedom. Conclusions These findings indicate that BRAF V600E-positive PLNTY exhibit characteristic clinical presentations but are not necessarily different in treatment responsiveness. Non-BRAF V600E tumors are more commonly associated with young patients.