The Site of Origin of Medulloblastoma: Surgical Observations Correlated to Molecular Groups

Area of Science:

• Pediatric neuro-oncology
• Developmental neurobiology
• Surgical oncology

Background:

• Medulloblastoma (MB) molecular subgroups (WNT, SHH, non-WNT/non-SHH) have distinct developmental origins.
• WNT-MB is hypothesized to originate from the embryonic lower rhombic lip (LRL).
• SHH-MB and other MB types are thought to arise from cerebellar precursor matrix regions.

Purpose of the Study:

• To analyze intraoperative site of origin (STO) data in pediatric medulloblastoma.
• To compare the intraoperatively determined STO with hypothesized embryological regions of origin for MB molecular groups.
• To evaluate the predictive value of neurosurgical inspection for MB molecular classification.

Main Methods:

• Retrospective review of 58 pediatric MB cases operated between 1996 and 2020.
• Analysis of detailed operative reports, surgical videos, and clinical/genetic data.
• Assessment of STO based on intraoperative neurosurgical findings.

Main Results:

• The intraoperatively assessed STO correctly predicted molecular groups in 20% of WNT-MB, 60% of SHH-MB, and 71% of non-WNT/non-SHH MB.
• Positive predictive values for STO were 0.21 for WNT-MB, 0.86 for SHH-MB, and 0.73 for non-WNT/non-SHH MB.
• Neurosurgical inspection showed limited accuracy in predicting the molecular group of medulloblastoma.

Conclusions:

• The intraoperatively observed STO has a limited predictive value for determining the molecular group of medulloblastoma.
• Accurate molecular subtyping of MB may require methods beyond intraoperative surgical assessment.
• Further research is needed to refine methods for predicting MB molecular groups during surgery.