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I read with interest the recent review by Soni et al, “Meningioma: Molecular Updates from the 2021 WHO Classification of CNS Tumors and Imaging Correlates(1). The authors provide a clear overview of histologic grading and emerging molecular insights. However, there are critical updates from cIMPACT-NOW Update 8 and recent studies that were not addressed and are essential for neuroradiologists aiming to stay current and contribute meaningfully to meningioma care.
First, cIMPACT-NOW Update 8 offers specific guidance on grading tumors that show benign histologic features but harbor high-risk molecular alterations. Notably, it proposes upgrading tumors with CNS WHO grade 1 morphology to grade 2 if combined 1p and 22q losses and/or NF2 variants are present(2). This underscores the importance of integrating chromosomal and molecular profiling into the risk assessment of meningiomas that appear histologically indolent.
Second, recent large-scale efforts have validated DNA methylation–based classifiers that outperform the 2021 WHO grading in predicting recurrence. These classifiers, now publicly available, stratify meningiomas into biologically and prognostically distinct groups—immunogenic, NF2-wildtype, hypermetabolic, and proliferative—with important implications for surveillance and treatment(3, 4).
Furthermore, recent metabolic profiling highlights that hypermetabolic and proliferative meningiomas harbor distinct metabolic signatures, such as N6-trimethyllysine, which correlate with outcomes (5). In addition, a recent study has shown that response to surgery and radiotherapy varies by molecular and metabolic subtype, and has the potential to meaningfully impact clinical decision making and treatment selection for patients (6).
These studies strongly support incorporating molecular data into treatment planning—a shift in which neuroradiologists should play an active role by identifying high-risk features, supporting radiogenomic modeling, and adopting advanced imaging protocols to guide biopsy, resection, and follow-up. In conclusion, while the AJNR review sets a strong foundation, future discussions must expand to include cIMPACT-NOW recommendations, methylation classifiers, and metabolic signatures. Neuroradiologists should be proactive not only in recognizing molecular imaging correlates but also in driving their clinical integration.
References
1. Soni N, Ora M, Bathla G, et al. Meningioma: Molecular Updates from the 2021 World Health Organization Classification of CNS Tumors and Imaging Correlates. AJNR Am J Neuroradiol. 2025;46(2):240–250. doi:10.3174/ajnr.A8368
2. Sahm F, Aldape KD, Brastianos PK, et al. cIMPACT-NOW update 8: Clarifications on molecular risk parameters and recommendations for WHO grading of meningiomas. Neuro Oncol. 2025;27(2):319–330.
3. Landry AP, Wang JZ, Patil V, et al. Validation and next-generation update of a DNA methylation–based recurrence predictor for meningioma: A multicenter prospective study. Neuro Oncol. 2024 Nov 6: noae236. doi: 10.1093/neuonc/noae236. Online ahead of print.
4. Landry AP, Wang JZ, Liu J, et al. Development and validation of a molecular classifier of meningiomas. Neuro Oncol. 2025 Jan 8:noae242. doi: 10.1093/neuonc/noae242. Online ahead of print.
5. Landry AP, Wang JZ, Yefet LS, et al. Metabolic profiling of meningioma reveals novel subgroup-specific biologic insights and outcome dependencies. Neuro Oncol
. 2025 Jan 24:noae281. doi: 10.1093/neuonc/noae281. Online ahead of print.
6. Wang JZ, Patil V, Landry AP, et al.Nature Medicine. Molecular classification to refine surgical and radiotherapeutic decision-making in meningioma. Nat Med. 2024;30:3173–3183.