Histopathologic risk factors for progression of atypical meningioma: a retrospective cohort study evaluating the impact and clinical value of mitotic count and Ki-67.

Abstract

Given the heterogeneity of atypical meningioma (AM) and potential interobserver variability in WHO grade assignment among pathologists, there is a need for more objective criteria to improve risk stratification. This study examined conventional and novel risk factors for AM progression, focusing on mitotic count (MC) and Ki-67, and explored their clinical relevance. This retrospective cohort study included 240 consecutive patients with AM surgically treated at a single tertiary institution between 2001 and 2020. The cut-off values for MC and Ki-67 were determined using the Youden index. Risk factors for progression were analyzed using cause-specific Cox proportional hazards models. Progression-free survival (PFS) was estimated using cumulative incidence function (CIF) and compared using the Gray's test. AM progression occurred in 32.5% of patients with a median time to progression of 25.2 months. The median follow-up was 42.3 months. While a clinically meaningful Ki-67 cut-off was not identified, MC ≥ 6 was significantly associated with AM progression. On multivariate analysis, age, gross total resection (GTR), MC ≥ 6, brain invasion, sheeting, and adjuvant radiotherapy (RTx) were associated with progression. RTx improved PFS in the subtotal resection (STR) group but not in the GTR group. Among GTR patients, those with MC ≥ 6 had worse outcomes. GTR and RTx may reduce the progression of AM. MC ≥ 6 significantly increases the risk of progression, even in GTR patients. RTx should be considered for all STR patients A more vigilant follow-up or consideration of RTx is warranted in GTR patients when a high MC is identified.