Meningiomas: Overview and New Directions in Therapy

Abstract and Introduction

Abstract

The majority of meningiomas, the most common primary brain tumor, are considered to be benign, and characteristic magnetic resonance imaging features allow a preliminary diagnosis. Meningiomas can be classified in the World Health Organization system as grade I, II, or III, depending on various histological features. In many cases, observation is the preferred management option, although this means the absence of a histological diagnosis. If necessary, standard therapy consists of surgery with or without adjuvant radiation, depending on the tumor grade and the degree of resection. To date, systemic therapies are not included in the standard of care. The level of evidence for treatment recommendations is low, and effective treatment regimens, especially for surgery-refractory and radiation-refractory meningiomas, are still very limited. Recent studies have broadened our knowledge of the genetics and pathogenesis of meningiomas and will lead to new therapeutic options. This review summarizes the epidemiology, pathogenesis and genetics, classification, and diagnosis of meningiomas, as well as management principles, including promising new avenues of therapy.

Introduction

Meningiomas are the single most common brain tumor, comprising 36.4% of all primary brain tumors.^[1] The vast majority, more than 90%, are considered nonmalignant or benign, and most meningiomas are solitary. They typically arise in the intracranial, intraspinal, or orbital locations, although rarely primary intraosseous and intraparenchymal meningiomas may occur.^[2] Despite being the most common primary brain tumor, relatively little is known about the pathogenesis of meningiomas. Standard therapy consisting of surgery with or without radiation is effective in controlling the majority of benign tumors, but effective treatments for surgery-refractory and radiation-refractory meningiomas are limited, with little data to support systemic treatments. Recently, however, an evolving understanding of the molecular and genetic landscape of meningiomas has led to new strategies in medical therapies that have the potential to decrease morbidity and mortality in subsets of patients.

Table 1. 2016 WHO classification of meningiomas[2]
WHO grade	Frequency	Pathological features	Histological subtypes	Rate of recurrence
I	80–90%		Meningothelial Fibrous Transitional Psammomatous Angiomatous Microcystic Secretory Lymphoplasmacyte-rich Metaplastic	7–25%
II	20–25%	Increased mitotic activity or Brain invasion or Three or more of the following: Increased cellularity Small cells with high nuclear-to-cytoplasmic ratio Prominent nucleoli Sheeting Foci of spontaneous necrosis	Chordoid Clear cell Atypical	29–52%
III	1–3%	Markedly elevated mitotic activity Malignant cytological features Extensive necrosis K_i-67 > 20%	Papillary Rhabdoid Anaplastic	50–94%

Abbreviation: WHO, World Health Organization.

Table 2. Simpson grading system[77]
Simpson grade	Definition	10-y recurrence rate
1	Macroscopic gross total resection with excisions of the dura, sinus, and bone	9%
2	Macroscopic gross total resection with coagulation of the dural attachment	19%
3	Macroscopic resection without resection or coagulation of the dural attachment	29%
4	Subtotal resection	40%
5	Biopsy	NA