脑膜瘤分子分型与DNA甲基化分层对神经外科诊疗决策的影响

Impact of Molecular Classification and DNA Methylation Stratification of Meningioma on Neurosurgical Decision-Making

摘要: 脑膜瘤在组织学形态、复发风险及治疗反应方面具有显著异质性，传统世界卫生组织(WHO)分级和Simpson切除分级虽仍是临床决策基础，但难以充分解释同级别肿瘤之间差异悬殊的生物学行为。2021年WHO中枢神经系统肿瘤分类首次将TERT启动子致癌性变异和CDKN2A/B纯合缺失纳入脑膜瘤3级判定，随后DNA甲基化分型、拷贝数变异及多组学整合模型进一步提高了复发预测的精度。近年的多中心研究显示，分子分型不仅可修正传统病理分级，还可能识别组织学低级别但分子高危的患者、区分完全切除后仍需强化随访或辅助放疗的亚群，并预测不同分子组对放疗的反应。与此同时，分子结果对手术策略的意义并非简单追求更激进切除：安全范围内的全切仍普遍改善局部控制，而硬膜附着处处理可能优于单纯肉眼全切；在关键神经血管结构受累时，分子风险更适合用于评估残留病灶的后续代价及辅助治疗需要，而不能作为舍弃功能进行过度切除的依据。本文围绕WHO分级演进、主要DNA甲基化分类体系、分子信息对切除范围、术后放疗、影像随访及复发再治疗决策的影响进行综述，并讨论检测流程、肿瘤内异质性、平台一致性、成本与证据外推等限制。现有证据支持将DNA甲基化分层作为组织病理学、影像学和切除程度之外的重要补充，但其常规应用仍需标准化报告、区域验证及分子分层前瞻性试验。

Abstract: Meningiomas show substantial heterogeneity in morphology, recurrence risk, and treatment response. Although World Health Organization (WHO) grade and extent of resection remain the foundation of clinical management, they do not fully account for the divergent behavior of tumors within the same histological category. The 2021 WHO classification incorporated oncogenic TERT promoter variants and homozygous CDKN2A/B deletion as molecular criteria for CNS WHO grade 3. DNA methylation classes, copy-number alterations, and integrated multi-omic models subsequently improved risk prediction beyond histology alone. Recent multicenter studies indicate that molecular profiling may identify histologically low-grade but biologically high-risk tumors, refine selection for postoperative radiotherapy, and guide surveillance after gross-total resection. Molecular data also provide a more nuanced interpretation of surgical extent: safe gross-total resection remains associated with improved local control, whereas aggressive dural excision does not necessarily outperform coagulation when functional risk is substantial. Thus, molecular risk should clarify the consequence of residual disease and the need for adjuvant therapy rather than justify unsafe radicality. This review summarizes current methylation-based and integrated classification systems and examines their impact on diagnosis, surgical strategy, radiotherapy, surveillance, and management of recurrent disease. Practical limitations—including intratumoral heterogeneity, tissue quality, platform calibration, classifier confidence, cost, and the lack of molecularly stratified prospective trials—are also discussed. DNA methylation stratification is an important adjunct to histopathology, imaging, and resection status, but standardized reporting and prospective validation are required before universal implementation.