The Discrepancy Between Standard Histologic WHO Grading of Meningioma and Molecular Profile: A Single Institution Series

Abstract

IntroductionMeningiomas are the most common primary central nervous system (CNS) tumor. They are most often benign, but a subset of these can behave aggressively. Current World Health Organization (WHO) guidelines classify meningiomas into three grades based on the histologic findings and presence or absence of brain invasion. These grades are intended to guide treatment, but meningiomas can behave inconsistently with regard to their assigned histopathological grade, influencing patient expectations and management. Advanced molecular profiling of meningiomas has led to the proposal of alternative molecular grading schemes that have shown superior predictive power. These include methylation patterns, copy number alterations, and mutually exclusive driver mutations affecting oncogenes, including BAP1, CDKN2A/B, and the TERT promoter, which are associated with particularly aggressive tumor biology. Despite the evident clinical value, advanced molecular profiling methods are not widely incorporated in routine clinical practice for meningiomas.ObjectiveTo assess the degree of concordance between the molecular profile of meningiomas and the histopathologic WHO classification, the current method of predicting meningioma behavior.MethodsIn a two-year single-institution experience, we used commercially available resources to determine molecular profiles of all resected meningiomas. Copy number aberrations and oncogenic driver mutations were identified and compared with the histopathologic grade.ResultsOne hundred fifty-one total meningioma cases were included for analysis (85.4% WHO grade 1, 13.3% WHO grade 2, and 1.3% grade 3). Chromosomal analysis of 124 of these samples showed that 29% of WHO grade 1 tumor featured copy number profiles consistent with higher grade meningioma, and 25% of WHO grade 2 meningiomas had copy number profiles consistent with less aggressive tumors. Furthermore, 8% harbored mutations in TERT, CDKN2A/B, or BAP1 of which 6% occurred in grade 1 meningiomas.ConclusionsRoutine advanced molecular profiling of all resected meningiomas using commercially available resources allowed for identification of a significant number of meningiomas whose molecular profiles were inconsistent with WHO grade. Our work shows the clinical value of integrating routine molecular profiling with histopathologic grading to guide clinical decision making.

Meningiomas with CNS invasion

“… Roehrkasse et al (2022) have reported data supporting the concept that the analysis of the molecular background of meningiomas may hold superior prognostic power when compared to histological features. Nassiri et al (2021) described four consensus molecular meningioma groups with distinct tumour behaviour.…”

“… Nassiri et al (2021) described four consensus molecular meningioma groups with distinct tumour behaviour. Comprehensive molecular profiling of meningiomas should probably include DNA methylation pattern and copy number aberration analyses, investigating mRNA abundance, as well as driver mutations of oncogenes, such as BAP1, CDKN2A/B , and the TERT promoter ( Louis et al, 2021 ; Nassiri et al, 2021 ; Roehrkasse et al, 2022 ). Maas et al reviewed DNA methylation and copy number aberrations in 3031 meningiomas, and studied mutation data of 858 meningiomas.…”

Surgical strategies for intracranial meningioma in the molecular era

“…CNV data can help predict tumor behavior with the degree of chromosomal abnormalities strongly associated in recurrence [56][57][58]. This information is relatively easy to acquire at most centers and enhances its usefulness.…”

“…While “higher risk” copy number profiles have been reported in 13–29% of grade 1 meningiomas, lesser degrees of percent genome altered are observed in some higher-grade meningiomas (Figs. 8 , 9 ) [ 56 , 58 ]. These discordances must be considered when making treatment decisions after surgery.…”

Somatostatin Receptor Targeted PET-Imaging for Diagnosis, Radiotherapy Planning and Theranostics of Meningiomas: A Systematic Review of the Literature

“…The World Health Organization (WHO) classified meningiomas into three different grades, on the basis of histologic findings and presence/absence of brain invasion: grade 1, grade 2 (atypical), and grade 3 (anaplastic) [ 2 ]. This classification is widely used for prognostic stratification and guiding therapeutic management, although emerging evidence suggests that, aside from classical WHO grading, molecular profile should be taken into account for a more accurate and patient’s tailored clinical management [ 3 ].…”