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  • Updated 05.05.2023
  • Released 06.27.1997
  • Expires For CME 05.05.2026




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.

Key points

• 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. There are ongoing studies to assess the safety and efficacy of targeted systemic agents.

• Molecular targets, such as NF2, AKT1, SMO, and CDK4/6 pathways, are involved in the pathogenesis of meningiomas, which may serve as potential therapeutic targets in the medical management of these challenging tumors.

TERT alterations are associated with aggressive biological behavior and poor outcome despite management with surgery and radiation.

Historical note and terminology

The word "meningioma" was first used by Cushing in 1922 to describe a tumor originating from the meninges (27). In 1938 Cushing and Eisenhardt, in a classic monograph, described a classification system for these tumors (28). Meningiomas originate from the arachnoidal cap cell, a meningothelial cell in the arachnoidal membrane. They generally arise where arachnoidal villi are numerous (60). 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 (28; 75; 104).

Meningiomas are classified according to the World Health Organization (WHO) grading scale as grade 1, grade 2, or grade 3, which corresponds to a more descriptive classification used clinically as benign, atypical, or malignant. The WHO classification has moved away from these descriptive names to the more straightforward numerical system. WHO grade 1 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 (60). Meningiomas immunostain with vimentin, desmoplakin, and epithelial membrane antigen. Meningiomas grow in three 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 two 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 nine meningioma subtypes are psammomatous, papillary, angiomatous, microcystic, secretory, clear cell, chordoid, lymphoplasmacyte-rich, and metaplastic. Although these subtypes have distinct histologic features, they have only limited impact on the natural history (some subtypes delineate tumors as WHO grade 2 or 3) and, at this time, do not impact treatment response.

WHO grade 2 meningiomas, also known as atypical meningiomas, include chordoid and clear cell subtypes (12). These tumors make up 5% to 7% of all meningiomas (81). Grade 2 meningiomas are diagnosed based on increased mitotic index of equal to or greater than four mitoses per 10 high-power fields or three 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" (17). The updated WHO classification system from 2016 includes “brain invasion” as criteria for WHO grade 2 meningiomas (73).

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 younger patients and occur more frequently in the spinal and cerebellar pontine region. The recurrence rate of clear cell meningiomas is 46% to 80% (119). In a large retrospective study of over 10,000 patients with meningiomas, clear cell meningiomas were more likely to be intraspinal rather than intracranial (72).

WHO grade 3 meningiomas make up 1.0% to 2.8% of all meningiomas. Grade 3 meningiomas are also known as anaplastic meningiomas or malignant meningiomas. These include anaplastic, rhabdoid, and papillary types (12). Grade 3 meningiomas have further increase in mitoses and cellularity with conspicuous necrosis (79). Twenty or more mitoses per 10 high-power fields is a defining characteristic of grade 3 meningiomas (17). Grade 2 and 3 meningiomas have a much higher recurrence rate after resection than benign meningiomas. Recurrence rates were 6.9% for grade 1 meningiomas, 34.6% for grade 2 meningiomas, and 72.7% for grade 3 meningiomas (79).

Papillary and rhabdoid meningiomas are rare variants and have an aggressive clinical course and higher rates of recurrence, metastases, and mortality (17). Papillary meningiomas generally occur in the pediatric population (12). 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 (59).

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