cIMPACT-NOW update 8: Clarifications on molecular risk parameters and recommendations for WHO grading of meningiomas

Abstract

Meningiomas are the most frequent primary intracranial tumors. Hence, they constitute a major share of diagnostic specimens in neuropathology practice. The 2021 WHO Classification of Central Nervous System Tumors ("CNS5") has introduced the first molecular grading parameters for meningioma with oncogenic variants in the TERT promoter and homozygous deletion of CDKN2A/B as markers for CNS WHO grade 3. However, after the publication of the new classification volume, clarifications were requested, not only on novel but also on long-standing questions in meningioma grading that were beyond the scope of the WHO "blue book." In addition, more recent research into possible new molecular grading parameters could not yet be implemented in the 2021 classification but constitutes a compelling body of literature. Hence, the consortium to inform molecular and practical approaches to CNS tumor taxonomy-not official WHO (cIMPACT-NOW) Steering Committee convened a working group to provide such clarification and assess the evidence of possible novel molecular criteria. As a result, this cIMPACT-NOW update provides guidance for more standardized morphological evaluation and interpretation, most prominently pertaining to brain invasion, identifies scenarios in which advanced molecular testing is recommended, proposes to assign CNS WHO grade 2 for cases with CNS WHO grade 1 morphology but chromosomal arm 1p deletion in combination with 22q deletion and/or NF2 oncogenic variants, and discusses areas in which the current evidence is not yet sufficient to result in new recommendations.

Keywords: WHO classification; cIMPACT-NOW; classification; grading; meningioma; molecular neuropathology.

Figure 1.

(A) CNS5 grading scheme with the molecular markers CDKN2A/CDKN2B and oncogenic variants in the TERT promoter as independent criteria for CNS WHO grade 3 independent of morphology. Select cases with CNS WHO grade 1 or 2, morphology, may benefit from additional molecular analyses for more precise risk assessment (Figure 2). (B) Overview of improved risk assessment approaches to meningioma with CNS WHO grade 1 or 2, morphology. * for 1p, deletions of >5 % have shown prognostic significance; for other chromosomal arms, insufficient data is available on whether a smaller than whole-arm deletion is also indicative of prognosis. **Specifically for brain-invasive otherwise benign (BIOB) meningioma, this update proposes to assign CNS WHO grade based on molecular markers.

Figure 2.

GFAP immunostains in a brain-invasive otherwise benign meningioma with entrapped reactive CNS tissue within the main tumor mass (left) and a meningioma with perivascular spread along Virchow–Robin spaces but no true parenchymal invasion with tumor extending beyond the pial barrier (right). Scale bar app. 200 µm.