[New developments in grading meningiomas: The experience of the Hospital Sainte-Anne]

Abstract

Introduction: The 2021 World Health Organisation (WHO) classification of tumours of the central nervous system introduced molecular biomarkers (homozygous deletion of CDKN2A/B and TERT promoter mutation) in the grading of meningiomas. Since, the cIMPACT-NOW consortium has proposed a new prognostic algorithm (published in the update 8), integrating epigenetic and genetic data. The aim of the study was to report on the experience of the neuropathology department of Sainte-Anne Hospital in integrating this algorithm into the gradingof meningiomas.

Materials and methods: This study included meningiomas diagnosed between 01/09/2024 and 30/04/2025, for which molecular analyses were mandatory according to the recommendations of the cIMPACT-NOW update 8. Next-generation sequencing (pTERT and CDKN2A/B status) and DNA-methylation analyses (methylation class and chromosomal copy number variations) were performed for each case.

Results: Seventy-one meningiomas were included. In 62% of cases, the grading was revised after integration of genetic and epigenetic data. In 35 cases, the final grade was lower than the initial grade, and in nine cases, the final grade was higher.

Discussion and conclusions: Invasion of the cerebral parenchyma alone no longer constitutes a criterion for grade 2. In our study, 47% of meningiomas graded as grade 2 solely on the basis of their invasive nature were downgraded to grade 1. The presence of a pTERT mutation and/or homozygous deletion of CDKN2A/B allowed two meningiomas initially graded as WHO grade 2 to be reclassified as grade 3. The presence of a combined loss of chromosomes 1p and 22q, associated with a grade 2 according to cIMPACT-NOW recommendations, led to the reclassification of four meningiomas initially considered to be grade 1. The cIMPACT-NOW update 8 has revolutionised pathologists' practice in grading meningiomas, with the need to integrate genetic and epigenetic data to morphological results.

Keywords: CDKN2A/B; Grade; Meningioma; Methylation profile; Méningiome; Méthylome; OMS; WHO; pTERT.