Proliferative Potential, and Inflammatory Tumor Microenvironment in Meningioma Correlate with Neurological Function at Presentation and Anatomical Location—From Convexity to Skull Base and Spine

SIMPLE SUMMARY: The World Health Organization (WHO) classification grades meningiomas exclusively due to their histopathological features. Meningiomas are predominantly benign intracranial entities, and surgical resection represents the therapy of choice. However, risk of progression and tailored scheduling of follow-up appointments are significantly influenced by various items, such as immunohistochemistry (e.g., MIB-1 index). Emerging evidence focuses attention on the anatomic location of meningiomas, especially regarding the differentiation between skull base and non-skull base meningiomas. In the present study, we therefore investigated demographic, histopathological, and laboratory variables regarding their association with the anatomic location. We found that spinal meningiomas have a significantly lower proliferative activity, less density of macrophage infiltrates, and a longer time to tumor progression. Moreover, increased MIB-1 indices are significantly associated with location-specific baseline symptoms (e.g., convexity: seizure burden, medial skull base: decreased vision, spinal: ambulatory ability). Therefore, anatomic location might be considered as a future subclassification in the grading of the prognosis of meningiomas. ABSTRACT: Emerging evidence emphasizes the prognostic importance of meningioma location. The present investigation evaluates whether progression-free survival (PFS), proliferative potential, World Health Organization (WHO) grades, and inflammatory burden differ between anatomical locations (skull base, non-skull base, and spinal) meningiomas. Five-hundred-forty-one patients underwent Simpson grade I or II resection for WHO grade 1 or 2 meningiomas. Univariable analysis revealed that spinal meningioma patients are significantly older, had a worse baseline Karnofsky Performance Status (KPS), higher acute-phase protein levels, lower incidence of WHO grade 2, lower mitotic counts, lower MIB-1 index, and less CD68(+) macrophage infiltrates. Multivariable analysis identified WHO grade 2 (OR: 2.1, 95% CI: 1.1–3.7, p = 0.02) and cranial location (OR: 3.0, 95% CI: 1.8–4.9, p = 0.001) as independent predictors of diffuse CD68(+) macrophage infiltrates. The mean PFS in cranial meningiomas was 115.9 months (95% CI: 107.5–124.3), compared to 162.2 months (95% CI: 150.5–174.0; log-rank test: p = 0.02) in spinal meningiomas. Multivariable Cox regression analysis revealed cranial location as an independent predictor (HR: 4.7, 95% CI: 1.0–21.3, p = 0.04) of shortened PFS. Increased MIB-1 indices ≥5% were significantly associated with location-specific deficits at presentation, such as decreased vision and seizure burden. Spinal meningiomas have a significantly longer PFS time and differ from the cranial meningiomas regarding MIB-1 index and density of tumor-associated macrophages.