WHO grade and pathological markers of meningiomas: Clinical and prognostic role

In recent years, WHO grading criteria have emerged as an inaccurate tool to correctly predict the risk of progression/recurrence for meningioma patients. Therefore, great efforts were made to find further prognostic factors that could predict the clinical course of meningiomas. Why morphological criteria are not able alone to correctly predict outcome in all patients? What are the biological parameters underlying a more aggressive behavior? Are there any molecular markers can be integrated in the risk assessment? Could new technologies, such as methylome profiling, contribute to provide additional tools in patients prognostic evaluation? We performed a literature review to find answers to these questions. Meningiomas have been demonstrated to be extremely heterogeneous neoplasms, also from the genetic and epigenetic standpoints. However, WHO Classification of Tumours of the central Nervous System 5th edition introduced only CDKN2A/B deletion and TERT promoter mutations as poor prognostic, grade 3 defining parameters. The different proposals of integrated grading, taking into account cytogenetic alterations and study of methylation profile, have not yet been incorporated in WHO grading criteria. Work in progress: this is the summary of current knowledge. Further studies are needed to expand the diagnostic and prognostic equipment to be integrated into clinical practice.