Dr. Dixit of Northwestern University Feinberg School of Medicine has no relevant financial relationships to disclose.)
Dr. Lukas of Northwestern University Feinberg School of Medicine received honorariums from Novocure for speaking engagements, honorariums from Novocure for advisory board membership, and research support from BMS.)
Meningiomas are the most common primary intracranial tumors. Although most are benign, morbidity can be high, and in some cases the tumor is fatal. The author reviews the pathophysiology, presentation, and treatment of this tumor, including new prognostic indicators in atypical and malignant meningiomas.
• Surgery and radiation form the cornerstones of therapeutic management of meningiomas.
• There are several pathways that are involved in meningioma formation and progression, Notch signaling pathway, and overexpression of SPARC protein.
• AKT1 and SMO pathways are involved in the pathogenesis of non-NF2 associated skull base meningiomas, which may serve as potential therapeutic targets in the medical management of these challenging tumors.
• Therapies targeting pathways involved in meningioma development and progression are actively undergoing evaluation.
Historical note and terminology
The word "meningioma" was first used by Cushing in 1922 to describe a tumor originating from the meninges (Cushing 1922). In 1938 Cushing and Eisenhardt, in a classic monograph, described a classification system for these tumors (Cushing and Eisenhardt 1962). Meningiomas originate from the arachnoidal cap cell, a meningothelial cell in the arachnoidal membrane. They generally arise where arachnoidal villi are numerous (Kleihues et al 1993). Meningiomas were classified by their site of origin, and this system is still used and is augmented by the neuroanatomically specific incidence of specific mutations within subtypes of meningiomas. The common sites of origin and incidence rates are shown in Table 1 (Cushing and Eisenhardt 1962; MacCarty and Taylor 1979; Rohringer et al 1989).
Meningiomas are classified as benign (WHO grade I), atypical (grade II), or malignant (grade III). All grades may invade bone producing both an osteoblastic and a lytic reaction (Kleihues et al 1993). There are numerous histologic subtypes, most of which do not influence the natural history. Some specific exceptions exist. WHO grade II meningiomas, also known as atypical meningiomas, include chordoid and clear cell subtypes (Bollag et al 2010). These tumors make up 5% to 7% of all meningiomas (McGovern et al 2010). Grade II meningiomas are diagnosed based on increased mitotic index of equal to or greater than 4 mitoses per 10 high-power fields or 3 or more of the following features: increased cellularity, small cells with high nuclear:cytoplasmic ratio, prominent nucleoli, uninterrupted patternless or sheet-like growth, and foci of "spontaneous" or "geographic necrosis" (Campbell et al 2009). The updated WHO classification system from 2016 includes “brain invasion” as criteria for WHO grade II meningiomas (Louis et al 2016).
WHO grade III meningiomas make up 1.0% to 2.8% of all meningiomas. Grade III meningiomas are also known as anaplastic meningiomas or malignant meningiomas. These include anaplastic, rhabdoid, and papillary histologic types (Bollag et al 2010). Grade III meningiomas have further increase in mitoses and cellularity with conspicuous necrosis (Maier et al 1992). Grade III meningiomas by definition must have equal to or greater than 20 mitoses per 10 high-power fields (Campbell et al 2009).
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