Pathology Unit, Department of Medical Sciences, University of Turin, Torino, Italy.
Pathology Unit, AOU Città della Salute e della Scienza di Torino, Torino, Italy.
J Neuropathol Exp Neurol. 2019 Mar 1;78(3):248-256. doi: 10.1093/jnen/nly127.
Higher-grade meningiomas (WHO grade II and III) represent a diagnostic and prognostic challenge. We assessed the pathological and molecular characteristics of 94 higher-grade meningiomas (85 grade II, 9 grade III) to identify novel prognostic parameters. Higher mitotic count (p = 0.018), diffuse (≥50%) prominent nucleoli (p < 0.001), and sheeting (p < 0.001) were associated with recurrence. Lower SSTR2a-positive cells median rate (p = 0.048) and TERT promoter mutations (p = 0.014) were associated with recurrence and patient death, respectively; further analyses did not identify other outcome associations. Presence of Ki67 hot spots was associated with a shorter progression-free survival (PFS), independently of WHO grade at multivariate analysis (HR = 3.35, p = 0.008). Necrosis was related to a poorer overall survival (OS) at univariate (focal: HR = 4.55, p = 0.041 and diffuse: HR = 7.38, p = 0.020) and Kaplan-Meier analyses. A prognostic score was designed based on previous results: Presence of diffuse (≥50%) prominent nucleoli (0/1 point), diffuse (≥50%) sheeting (0/1 point), focal (<50%) or diffuse (≥50%) necrosis (0/1/2 points), and Ki67 hot spots (0/1 point). A total score ≥4 predicted poorer PFS and OS by Kaplan-Meier (PFS: 1.7 vs 6.4 years, p < 0.001 and OS: 5.2 vs 10.8 years, p = 0.001) and multivariate (PFS: HR = 5.98, p < 0.001 and OS: HR = 2.99, p = 0.048) analyses. These results were confirmed in an independent series of 58 grade II meningiomas (PFS: HR = 7.22, p = 0.002 and OS: HR = 9.69, p = 0.003). These associations and the integrated score could complement WHO grading.
高级别脑膜瘤（WHO 分级 II 和 III）具有诊断和预后挑战性。我们评估了 94 例高级别脑膜瘤（85 例 II 级，9 例 III 级）的病理和分子特征，以确定新的预后参数。较高的有丝分裂计数（p=0.018）、弥漫性（≥50%）显著核仁（p<0.001）和片状（p<0.001）与复发相关。较低的 SSTR2a 阳性细胞中位数率（p=0.048）和 TERT 启动子突变（p=0.014）分别与复发和患者死亡相关；进一步分析未发现其他与结果相关的因素。Ki67 热点的存在与无进展生存期（PFS）较短相关，在多变量分析中独立于 WHO 分级（HR=3.35，p=0.008）。坏死与单因素分析中的总生存期（OS）较差相关（局灶性：HR=4.55，p=0.041；弥漫性：HR=7.38，p=0.020）和 Kaplan-Meier 分析。根据先前的结果设计了一个预后评分：弥漫性（≥50%）显著核仁（0/1 分）、弥漫性（≥50%）片状（0/1 分）、局灶性（<50%）或弥漫性（≥50%）坏死（0/1/2 分）和 Ki67 热点（0/1 分）。总评分≥4 通过 Kaplan-Meier（PFS：1.7 与 6.4 年，p<0.001 和 OS：5.2 与 10.8 年，p=0.001）和多变量（PFS：HR=5.98，p<0.001 和 OS：HR=2.99，p=0.048）分析预测较差的 PFS 和 OS。这些结果在 58 例 II 级脑膜瘤的独立系列中得到了证实（PFS：HR=7.22，p=0.002 和 OS：HR=9.69，p=0.003）。这些关联和综合评分可以补充 WHO 分级。
