What are meningiomas?

Related conditions:
Intracranial and spinal tumors, extra-axial brain tumors, neurofibromatosis

Definition:
Meningiomas are tumors of the meninges, the thin layers of tissue that surround the brain and spinal cord. This type of neoplasm most likely originates from cells of the arachnoid matter, the middle element of the three meningeal coverings, and occur mainly at the base of the brain and around the cerebral convexities. Meningiomas are visibly demarcated from the brain tissue and thus are classified as extra-axial tumors. They can extend from the surface of the dura matter, the outer meningeal layer, and erode the cranial bones, causing exostosis, or growth of the bone. In general, these are solitary lesions, and, as reported by the American Society of Clinical Oncology in 2014, about 80 percent of them are benign. However, multiple lesions are common in patients with neurofibromatosis type 2 (NF2), a genetic disorder that affects the nervous system. Several different histological types have been described, with the meningothelial, fibrous, and transitional forms as the most frequently found.

Risk factors: Although the risk factors for meningiomas are largely unknown, evidence suggests an association of risk with a family or personal history of neurofibromatosis type 2, exposure to ionizing radiation (during full-mouth dental radiographs), and use of sex hormones (oral contraceptives or hormone replacement therapy). Other risks factors that have been explored without conclusive results are head trauma, cell phone use, breast cancer, and allergic diseases.

Etiology and the disease process: The precise origin of the majority of the meningiomas is uncertain. However, several forms of this disease are clearly associated with the loss of a tumor-suppressor gene on chromosome 22, known as merlin and encoded by the NF2 gene. Merlin belongs to the 4.1 family of proteins, a group of molecules with roles in maintaining cell structure. Genetic defects in merlin account for many sporadic meningioma cases. In addition to merlin, other members of the 4.1 protein family with tumor-suppression activity have been involved in meningioma initiation (for example, 4.1B and 4.1R). However, meningioma progression seems to involve genetic changes in chromosomes other than chromosome 22.

The presence of a high density of progesterone receptors in the vast majority of meningiomas suggests a functional role of progesterone-signaling pathways in the pathogenesis and might explain the twofold and tenfold higher incidence respectively of cranial and spinal meningiomas in women. Other proteins that might participate in the disease process of meningioma include telomerase, transforming growth factor-beta, and somatostatin.

Incidence: Meningiomas are the most common nonglial and most common extra-axial tumors of the brain, with an incidence rate of approximately 7 per 100,000 individuals, according to the American Society of Clinical Oncology in 2014. The relatively frequent autopsy finding of small asymptomatic undiagnosed meningiomas suggests that the actual incidence rate is significantly higher. According to the American Brain Tumor Association's 2012 statistics, meningiomas are about twice as common in women, and the highest incidence is observed beginning in the sixth decade of life. Childhood cases of meningioma are rare.

Symptoms: Symptoms of meningiomas depend on the location and size of the lesion and result from increased intracranial pressure and edema of the brain structures adjacent to the tumor. The most common symptoms are headache, unilateral sensory disturbances (for example, hearing or visual loss), vertigo, imbalance, focal seizures, spastic weakness, numbness of the limbs, and painless proptosis or “bulging” eyes, among others.

Screening and diagnosis: No screening tests are available. The tendency of meningiomas to calcify and their abundant blood supply allow their diagnosis by contrast-enhanced computed tomography (CT), magnetic resonance imaging (MRI), and arteriography. On both CT and MRI scans, meningiomas appear as homogeneous, smoothly outlined masses, with attachments to the dura matter. Their extra-axial location differentiates them from common intra-axial tumors of the central nervous system, and their unique image density characteristics differentiate them from Schwannoma, another extra-axial tumor.

The World Health Organization (WHO) classifies meningiomas into three grades based on their histological features and the likelihood of recurrence.

• Grade I: benign meningiomas, with low risk of recurrence and aggressive growth





• Grade II: Atypical meningiomas, with greater risk of recurrence and aggressive growth





• Grade III: anaplastic or malignant meningiomas, with the greatest risk of recurrence and aggressive growth

Some 80 percent of all meningiomas are of WHO Grade I on diagnosis, according to the American Cancer Society in 2014.

Treatment and therapy: The primary treatment is complete surgical excision of the tumor. Focused radiation by Gamma Knife or proton beam is used when the lesion is located around vital structures or when it is a high-grade or recurrent tumor. Although effective chemotherapy has not yet been developed, studies on the use of hormonal antagonists and other molecules are ongoing.

Prognosis, prevention, and outcomes: Complete removal of the tumor is achieved in many cases, and in most patients, hearing and other functions of the nervous system are preserved. Recurrence depends on the grade of the tumor, ranging from 7 to 25 percent for noncancerous tumors to between 29 and 52 percent for atypical meningiomas, according to the American Society of Clinical Oncology as of 2014. Prevention of meningiomas is difficult since the etiology is poorly understood.

Backer-Grøndahl, Bjørnar H. Moen, and Sverre H. Torp. "The Histopathological Spectrum of Human Meningiomas." International Journal of Clinical & Experimental Pathology 5.3 (2012): 231–42. Web. 29 Oct. 2014.

Claus, Elizabeth B., et al. “Epidemiology of Intracranial Meningioma.” Neurosurgery 57.6 (2005): 1088–95. Print.

DeMonte, Franco, Michael W. McDermott, and Ossama Al-Mefty, ed. Al-Mefty's Meningiomas. New York: Thieme, 2011. Print.

Hyat, M. A., ed. Meningiomas and Schwannomas. New York: Springer, 2012. Print. Tumors of the Central Nervous System 7.

Lusis, Eriks, and David H. Gutmann. “Meningioma: An Update.” Current Opinion in Neurology 17.6 (2004): 687–92. Print.

Riemenschneider, Markus J., Arie Perry, and Guido Reifenberger. “Histological Classification and Molecular Genetics of Meningiomas.” Lancet Neurology 5 (2006): 1045–54. Print.