Atypical meningioma: Histopathological, genetic, and epigenetic features to predict recurrence risk

Grading assessed according to World Health Organization (WHO) criteria is a major prognostic factor for determining the risk of recurrence in patients with meningiomas and establishing the most appropriate therapeutic strategy after surgery. However, the main issue is to predict the recurrence risk of WHO grade 2 meningioma and, more specifically, of the atypical subtype. Indeed, owing to a reported recurrence rate of 50%, either radiotherapy or observation is currently considered an option after gross total surgical resection of atypical meningiomas. These heterogeneous clinical outcomes are likely related to the broad histopathological diagnostic criteria for this subtype, and whether meningiomas only present as brain invasion should be classified as atypical remains controversial. Over the last few years, several studies have shown that DNA methylation profiling, next-generation sequencing, and transcriptomics can better stratify meningiomas for their recurrence risk than histology. The main limitations to the widespread use of these approaches to classify meningiomas are their high cost and the need for sophisticated technologies. However, all studies concurred that atypical meningiomas without chromosome 1p deletion display a low recurrence risk, suggesting that the assessment of this cytogenetic alteration could represent an easy and quick method to determine which patients could benefit from adjuvant treatment after surgery. In addition, prognostically unfavorable molecular groups can be distinguished using specific immunostainings, although further validation is required.