Mutation Status and Epithelial Differentiation Stratify Recurrence Risk in Chordoid Meningioma—A Multicenter Study with High Prognostic Relevance

Abstract

Chordoid meningioma is a rare WHO grade II histologic variant. Its molecular alterations or their impact on patient risk stratification have not been fully explored. We performed a multicenter, clinical, histological, and genomic analysis of chordoid meningiomas from 30 patients (34 tumors), representing the largest integrated study to date. By NHERF1 microlumen immunohistochemical detection, three epithelial differentiation (ED) groups emerged: #1/fibroblastic-like, #2/epithelial-poorly-differentiated and #3/epithelial-well-differentiated. These ED groups correlated with tumor location and genetic profiling, with <i>NF2</i> and chromatin remodeling gene mutations clustering in ED group #2, and <i>TRAF7</i> mutations segregating in ED group #3. Mutations in <i>LRP1B</i> were found in the largest number of cases (36%) across ED groups #2 and #3. Pathogenic <i>ATM</i> and <i>VHL</i> germline mutations occurred in ED group #3 patients, conferring an aggressive or benign course, respectively. The recurrence rate significantly correlated with mutations in <i>NF2</i>, as single gene, and with mutations in chromatin remodeling and DNA damage response genes, as groups. The recurrence rate was very high in ED group #2, moderate in ED group #3, and absent in ED group #1. This study proposes guidelines for tumor recurrence risk stratification and practical considerations for patient management.