De novo and secondary anaplastic meningiomas: a study of clinical and histomolecular prognostic factors

Abstract

Background: Following recent studies underlining the differences between de novo and secondary anaplastic meningiomas and the prognostic value of telomerase reverse transcriptase (TERT) promoter mutation, we decided to conduct a multicenter retrospective study to address these questions and determine specific prognostic factors in each of these 2 anaplastic meningioma subgroups.

Methods: Among the 68 meningioma cases initially selected, only 57 were confirmed as anaplastic meningiomas after centralized pathological review. TERT promoter mutation analysis was performed in all cases.

Results: Median overall survival was 2.6 years and 5-year survival rate was 10%. This study confirmed the better prognosis of de novo anaplastic meningiomas (28 tumors) compared with secondary anaplastic meningiomas (29 tumors) (P = 0.02). In the "de novo" group, meningiomas diagnosed on histological anaplasia alone had a better prognosis than those in patients with a high number of mitoses with or without anaplasia (P = 0.01). In the "secondary" group, tumors demonstrate very heterogeneous clinical courses leading to malignant transformation, and time to first relapse as a low-grade tumor was a strong predictor of overall survival (P = 0.0007). TERT promoter mutation in anaplastic meningiomas was rare (14%) and did not influence overall survival but was associated with a shorter recurrence-free survival in the secondary anaplastic meningioma subgroup (P = 0.02). The absence of TERT promoter methylation, although rare (3/33 cases), may be associated with prolonged overall survival (P = 0.02).

Conclusion: This study highlights the different prognoses of de novo and secondary anaplastic meningiomas with specific prognostic factors in each subgroup. The analysis of TERT mutation and methylation could provide additional prognostic insights.

Fig. 1

(A) Anaplastic meningioma harboring numerous mitoses (>20 / 1.6 mm²) (arrows) and moderate atypia with prominent nuclei (hematoxylin, eosin, and saffron; original magnification: x400). (B) Anaplastic meningioma showing overt anaplasia, with pseudocarcinomatous features, necrosis, and numerous mitoses (>20 / 1.6 mm²; insert, arrows) (hematoxylin, eosin, and saffron; x100; insert: x400). (C) Same case: high Ki-67 proliferative index (immunohistochemistry, x200).

Fig. 2

Flow chart of histomolecular analysis of anaplastic meningiomas. For secondary anaplastic meningiomas, the number of relapses before anaplastic transformation is represented by the number of arrow lines between low-grade and anaplastic tumors. For example, 2 patients experienced 4 relapses before undergoing malignant transformation.

Fig. 3

Survival analysis of anaplastic meningiomas. (A) Overall survival of de novo vs secondary anaplastic meningiomas. (B) Overall survival of secondary anaplastic meningiomas depending on time to first relapse from a low-grade meningioma. (C) Overall survival of de novo anaplastic meningiomas depending on mitotic count. High mitotic count: meningiomas presenting with >20 mitoses per 10 HPF with or without associated anaplasia. Low mitotic count: meningiomas presenting with <20 mitoses per 10 HPF but with frank anaplasia. (D) Progression-free survival of secondary anaplastic meningiomas depending on TERT promoter mutation status. sec = secondary; m.c. = mitotic count. mut = mutant; wt = wild-type. Numbers of subjects at risk are indicated below plots at time points 0, 50, and 100 months.