The most frequent acquired genetic defects of meningiomas are truncating (inactivating) mutations in the neurofibromatosis 2 gene (merlin) on chromosome 22q. These are present in the great majority of certain meningiomas (e.g., fibroblastic and transitional types), but not others. Merlin deletions probably also play a role in those instances in which there is a loss of the long arm of chromosome 22. In meningiomas of both the sporadic and neurofibromatosis type 2 (NF2)–associated types, other somatic genetic defects are found, including deletions on chromosomes 1p, 6q, 9p, 10q, 14q, and 18q.
Meningiomas also elaborate a variety of soluble proteins, some of which (VEGF) are angiogenic and probably relate to both the highly vascularized nature of these tumors and their prominent surrounding edema (see Lamszus for further details). Some meningiomas contain estrogen and progesterone receptors. These findings may relate to the increased incidence of the tumor in women, its tendency to enlarge during pregnancy, and an association with breast cancer.
The precise cellular origin of meningiomas is still not settled. According to Rubinstein, they may arise from dural fibroblasts, but it was the opinion of our colleague
R.D. Adams that, they are more clearly derived from arachnoidal (meningothelial) cells, in particular from those forming the arachnoid villi. Because the clusters of arachnoidal cells penetrate the dura in largest number in the vicinity of venous sinuses, these are the sites of predilection for the tumor. Grossly, the tumor is firm, gray, and sharply circumscribed, taking the shape of the space in which it grows; thus, some tumors are flat and plaque-like, others round and lobulated. They may indent the brain and acquire a pia-arachnoid covering as part of their capsule, but they are clearly demarcated from the brain tissue (extraaxial) except in the unusual circumstance of a malignant invasive meningioma. Infrequently, they arise from arachnoidal cells within the choroid plexus, forming an intraventricular meningioma.
The cells of meningiomas are relatively uniform, with round or elongated nuclei, visible cytoplasmic membrane, and a characteristic tendency to encircle one another, forming whorls and psammoma bodies (laminated calcific concretions). A notable electron microscopic characteristic is the formation of very complex interdigitations between cells and the presence of desmosomes (Kepes). Cushing and Eisenhardt and, more recently, the World Health Organization (Lopes et al) have divided meningiomas into many subtypes depending on their mesenchymal variations, the character of the stroma, and their relative vascularity, but the value of such classifications is debatable. Currently neuropathologists recognize a meningothelial (syncytial) form as being the most common. It is readily distinguished from other similar but nonmeningothelial tumors such as hemangiopericytomas, fibroblastomas, and chondrosarcomas.