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 AbbVie as a guest speaker, from NewLink Genetics and Reneuron for consulting work, and from Monetris as an advisory board member.)
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.
• 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.
• Many meningiomas can be followed clinically and radiographically and may not require therapeutic intervention.
• Surgery and radiation form the cornerstones of therapeutic management of meningiomas.
• 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, atypical, or malignant. Benign meningiomas are not encapsulated; they grow invaginating, but demarcated, from the brain. They grow with finger-like projections, and penetrate surrounding mesenchymal tissue, including bone. They may produce both an osteoblastic and a lytic reaction (Kleihues et al 1993). Meningiomas immunostain with vimentin, desmoplakin, and epithelial membrane antigen. Meningiomas grow in 3 primary histologic patterns: (1) meningothelial, (2) fibroblastic, or (3) transitional, a combination of meningothelial and fibrous. Meningothelial meningiomas consist of lobules of cells with oval pale nuclei, with chromatin marginated around the nucleus. Fibroblastic meningiomas have parallel interlacing bundles of spindle-shaped cells with abundant collagen and reticulin between cells. Whorl formation and psammoma bodies are infrequent in these 2 histologic pattern types. Transitional meningiomas have a mixed pattern of both meningothelial and fibroblastic features. They more often contain whorls or psammoma bodies. The other 9 meningioma subtypes are psammomatous, papillary, angiomatous, microcystic, secretory, clear cell, chordoid, lymphoplasmacyte-rich, and metaplastic.
WHO grade II meningiomas, also known as atypical meningiomas, include chordoid and clear cell subtypes (Bollag et al 2010). Grade II meningiomas are also known as atypical meningiomas. These tumors make up 5% to 7% of all meningiomas (McGovern et al 2010). Atypical 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).
Clear-cell meningiomas make up only 0.2% of all meningiomas. This type usually behaves aggressively and can metastasize to the CSF. Clear-cell meningiomas often occur in patients of younger age and occur more frequently in the spinal and cerebellar pontine region. Recurrence rate of clear-cell meningiomas is 46% to 80% (Tong-tong et al 2010). In 1 large retrospective study of over 10,000 patients with meningiomas, clear cell meningiomas were more likely to be intraspinal rather than intracranial (Li 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 types (Bollag et al 2010). Malignant meningiomas have further increase in mitoses and cellularity with conspicuous necrosis (Maier et al 1992). Anaplastic meningiomas by definition must have equal to or greater than 20 mitoses per 10 high-power fields (Campbell et al 2009). Atypical and malignant meningiomas have a much higher recurrence rate after resection than do benign meningiomas. Recurrence rates were 6.9% for benign meningiomas, 34.6% for atypical meningiomas, and 72.7% for malignant meningiomas (Maier et al 1992).
Papillary and rhabdoid meningiomas are rare variants and have an aggressive clinical course and higher rates of recurrence, metastases, and mortality (Campbell et al 2009). Papillary meningiomas generally occur in the pediatric population (Bollag et al 2010). Their cell processes terminate in papilla on blood vessels, with tapering of their processes to form pseudorosettes. Rhabdoid meningioma is a new pathologic variant of malignant meningioma with peritumoral edema, bone involvement, and significant cystic components on MRI (Kim et al 2007).
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