Testing Meningiomas With Methylation Arrays: Insights and Recommendations From a Large Single-Centre Study.

in Neuropathology and applied neurobiology by Fernanda Ruiz, Rossella Rispoli, Zane Jaunmuktane, Ashirwad Merve, Linda D'Antona, Monika Dutt, Felix Sahm, Sebastian Brandner

TLDR

  • The study analyzed over 1000 meningiomas to investigate the relationship between WHO grade, methylation class, and copy number profile and recurrence risk.
  • The results suggest that Grade 2 and 3 meningiomas should be prioritized for methylation profiling, and a small proportion of Grade 1 meningiomas may also benefit from integrated molecular analysis.

Abstract

Meningiomas are common primary CNS tumours, and their morphological diagnosis is usually straightforward. Their histological grading according to CNS WHO criteria alone provides limited information on recurrence risk. Risk stratification of meningiomas combining WHO grade, methylation class and copy number profile improves prediction of the risk of early recurrence. Because of the frequency of meningiomas in diagnostic practice, applying this prediction algorithm to all meningiomas is financially not viable in most healthcare systems. We analysed a retrospective dataset of over 1000 meningiomas from a single centre with methylation arrays to provide guidance on which meningiomas to prioritise for integrated molecular testing and to understand how WHO grades resolve into risk strata. Approximately 90% of CNS WHO Grade 1 meningiomas were allocated into the methylation class 'benign' and also into a low-risk group. Grade 2 meningiomas were allocated almost equally to either the low-risk (39%) or intermediate-risk groups (46%) but occasionally also to the high-risk group (15%). All grading criteria for CNS WHO Grade 2 meningiomas (brain invasion, mitotic count, cytoarchitectural atypia and histological type) showed a similar risk score distribution as the entire group. Grade 3 meningiomas were allocated to intermediate- (26%) or high-risk groups (74%). Our data suggest that Grade 2 and 3 meningiomas should be prioritised for methylation profiling. A small proportion of Grade 1 meningiomas may also benefit from integrated molecular analysis, and further research is needed to explore if those histologically benign meningiomas with a predicted increased recurrence risk are associated with distinct demographic or histological characteristics.

Overview

  • The study aimed to investigate whether the WHO grade, methylation class, and copy number profile of meningiomas could be used to predict recurrence risk and identify those that would benefit from integrated molecular testing.
  • The study retrospectively analyzed a dataset of over 1000 meningiomas from a single center to provide guidance on which meningiomas to prioritize for integrated molecular testing and to understand how WHO grades resolve into risk strata.
  • The primary objective of the study was to identify the optimal approach for risk-stratification of meningiomas and to determine which meningiomas would benefit from additional molecular testing.

Comparative Analysis & Findings

  • The results showed that WHO Grade 1 meningiomas were mostly allocated to the 'benign' methylation class and low-risk group, but a small proportion may benefit from integrated molecular analysis.
  • Grade 2 meningiomas were allocated almost equally to the low-risk and intermediate-risk groups, but a small proportion were also allocated to the high-risk group.
  • Grade 3 meningiomas were mostly allocated to the high-risk group, but a small proportion were also allocated to the intermediate-risk group.

Implications and Future Directions

  • The study suggests that Grade 2 and 3 meningiomas should be prioritized for methylation profiling, as they are at higher risk of recurrence.
  • A small proportion of Grade 1 meningiomas may also benefit from integrated molecular analysis, and further research is needed to identify distinct demographic or histological characteristics that may predict increased recurrence risk.
  • The study's findings have implications for the diagnosis and management of meningiomas, and may inform the development of new guidelines for the risk-stratification and treatment of these tumors.
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