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Prognostic Characterization of Higher-Grade Meningiomas: A Histopathological Score to Predict Progression and Outcome

Luca Bertero¹, Giulia Dalla Dea¹, Simona Osella-Abate¹

¹Pathology Unit, Department of Medical Sciences, University of Turin, Torino, Italy.

Journal of Neuropathology and Experimental Neurology

|January 29, 2019

Abstract:

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.

Insights

Higher-grade meningiomas (WHO grade II and III) have new prognostic markers. A scoring system combining nucleoli, sheeting, necrosis, and Ki67 hot spots predicts recurrence and survival, aiding clinical decisions.

Area of Science:

Neuro-oncology
Pathology
Molecular Biology

Background:

Higher-grade meningiomas (WHO grade II and III) present significant diagnostic and prognostic challenges.
Accurate prognostication is crucial for effective patient management and treatment planning.

Purpose of the Study:

To identify novel pathological and molecular prognostic parameters for higher-grade meningiomas.
To develop and validate an integrated prognostic score to complement existing WHO grading.

Main Methods:

Retrospective analysis of 94 higher-grade meningiomas (WHO grade II/III) for pathological and molecular features.
Assessment of associations between features (mitotic count, nucleoli, sheeting, SSTR2a, TERT promoter mutations, Ki67 hotspots, necrosis) and clinical outcomes (recurrence, progression-free survival [PFS], overall survival [OS]).
Development and validation of a prognostic score based on significant parameters in an independent cohort of 58 grade II meningiomas.

Main Results:

Higher mitotic count, diffuse prominent nucleoli, and sheeting were linked to recurrence.
Lower SSTR2a-positive cells and TERT promoter mutations correlated with recurrence and patient death, respectively.
Ki67 hotspots and necrosis were independent predictors of shorter PFS and OS, respectively.
An integrated prognostic score (nucleoli, sheeting, necrosis, Ki67 hotspots) effectively predicted poorer PFS and OS in both cohorts.

Conclusions:

Pathological features like prominent nucleoli, sheeting, necrosis, and Ki67 hotspots are critical prognostic indicators for higher-grade meningiomas.
The developed integrated prognostic score shows strong predictive power for PFS and OS, complementing WHO grading.
These findings offer valuable tools for refining prognostication and guiding clinical decisions in higher-grade meningioma management.

Read full analysis

Keywords:

Ki67 Meningioma Prognosis Prognostic factors SSTR2a Score TERT

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