The site of origin of medulloblastoma: Does the neurosurgical perspective support the current concept from molecular data?

Abstract

Abstract Purpose Developmental gene expression data from medulloblastoma (MB) supported by retrospective MR imaging studies suggest that WNT-MB originate from the region of the embryonic lower rhombic lip (LRL), whereas SHH-MB and non-WNT/non-SHH-activated MB arise from cerebellar precursor matrix regions. This study aims to analyze detailed intraoperative data with regard to the site of origin (STO) and compare these findings with the hypothesized regions of origin associated with the molecular group. Methods A review of the institutional database identified 58 pediatric patients who were operated on a MB at our department between 1996 and 2020 and had a detailed operative report, surgical video as well as clinical and genetic classification data available for analysis. The STO was assessed based on intraoperative findings of an expert neurosurgeon blinded to the molecular group information. Results Using the intraoperatively defined STO, “correct” prediction of molecular groups was feasible in 20% of WNT-MB, 60% of SHH-MB and 71% of non-WNT/non-SHH activated MB. The positive predictive values of the neurosurgical inspection to detect the molecular group were 0.21 (95% CI 0.08–0.48) for WNT-MB, 0.86 (95% CI 0.49–0.97) for SHH-MB and 0.73 (95% CI 0.57–0.85) for non-WNT/non-SHH activated MB. Conclusions The present study demonstrated a limited predictive value of the intraoperatively observed STO for the prediction of the molecular group of MB. Thus, our findings challenge the current concept of the molecular group-specific origins based on developmental gene expression data and neuroradiological STO definitions.