Meningioma

The word meningioma was first used by Cushing in 1922 to describe a tumor originating from the meninges. Meningiomas are the second most common primary neoplasm of the central nervous system, arising from the arachnoid "cap" cells of the arachnoid villi in the meninges. These tumors are usually benign in nature; however, they can be malignant.

Causes
Most cases are sporadic while some are familial. Persons who have undergone radiation to the scalp are more at risk for developing meningiomas.

The most frequent genetic mutations involved in meningiomas are inactivation mutations in the neurofibromatosis 2 gene (merlin) on chromosome 22q.

Other possible genes/loci include:
 * MN1
 * PTEN
 * an unknown gene at 1p13

Signs and symptoms
Small tumors (e.g., < 2.0 cm) are usually incidental findings at autopsy without having caused symptoms. Larger tumors can cause symptoms depending on the size and location.
 * Focal seizures may be caused by meningiomas that overlie the cerebrum.
 * Progressive spastic weakness in legs and incontinence may be caused by tumors that overlie the parasagittal frontoparietal region.
 * Sylvian tumors may cause myriad motor, sensory, aphasic, and seizure symptoms, depending on the location.
 * Increased intracranial pressure eventually occurs, but is less frequent than in gliomas.

Mechanism
Meningiomas arise from arachnoidal cells, most of which are near the vicinity of the venous sinuses, and this is the site of greatest prevalence for meningioma formation. They are most frequently attached to the dura over the superior parasagittal surface of frontal and parietal lobes, along the sphenoid ridge, in the olfactory grooves, the sylvian region, superior cerebellum along the falx cerebri, cerebellopontine angle, and the spinal cord. The tumor is usually gray, well-circumscribed, and takes on the form of space it occupies. They are usually dome-shaped, with the base lying on the dura.

Histologically, the cells are relatively uniform, with a tendency to encircle one another, forming whorls and psammoma bodies (laminated calcific concretions). They have a tendency to calcify and are highly vascularized.

Meningiomas are often considered benign tumors curable by surgery, but most recurrent meningiomas correspond to histologic benign tumors. The metabolic phenotype of these benign recurrent meningiomas indicated an aggressive metabolism resembling that observed for atypical meningioma.

Diagnosis
Meningiomas are readily visualized with contrast CT, MRI with gadolinium, and arteriography, all attributed to the fact that meningiomas are extra-axial and vascularized. CSF protein is usually elevated if lumbar puncture is attempted.

Though the majority of meningiomas are benign, they can have malignant presentations. Classification of meningiomas are based upon the WHO classification system. In a recent retrospective review of atypical and anaplastic meningioma cases, the mean overall survival for atypical meningiomas was found to be 11.9 years vs. 3.3 years for anaplastic meningiomas. Mean relapse free survival for atypical meningiomas was 11.5 years vs. 2.7 years for anaplastic meningiomas.
 * Benign (Grade I) - (90%) - meningothelial, fibrous, transitional, psammomatous, angioblastic (most aggressive)
 * Atypical (Grade II) - (7%) - chordoid, clear cell, atypical (includes brain invasion)
 * Anaplastic/malignant (Grade III) - (2%) - papillary, rhabdoid, anaplastic

Malignant Anaplastic meningioma is an especially malignant tumor with aggressive behavior. Even if - by general rule - neoplasms of the nervous systems (brain tumors) cannot metastasize into the body (because of the blood-brain barrier) Anaplastic Meningioma can. Although they are inside the cerebral cavity, they are located on the bloodside of the BBB, because meningioma tend to "connect" themselves to bloodvessels to "feed". Cancerized cells can escape into the bloodstream. This is why meningioma when they metastasize often turn up around the lungs. It should be noted that Anaplastic meningioma and hemangiopericytoma are difficult to distinguish (even by pathological means), as they look similar, especially if the first occurrence is a meningeal tumor, and both tumors occur in the same places (same type of tissue)

Observation
Observation with close imaging follow-up can be used in select cases if a meningioma is small and asymptomatic. In a retrospective study on 43 patients, 63% of patients were found to have no growth on follow-up, and the 37% found to have growth grew at an average of 4 mm / year. In this study, younger patients were found to have tumors that were more likely to grow on repeat imaging, thus are poorer candidates for observation. In another study, clinical outcomes were compared for 213 patients undergoing surgery vs. 351 patient under watchful observation. Only 6% of the conservatively treated patients later developed symptoms, while among the surgically treated patients, 5.6% developed persistent morbid condition, and 9.4% developed surgery-related morbid condition.

Observation is not recommended in tumors already causing symptoms. Furthermore, close follow-up with imaging is required with an observation strategy to rule out an enlarging tumor.

Surgical resection
Meningiomas can usually be surgically resected with permanent cure if the tumor is superficial on the dural surface and easily accessible. Transarterial embolization has become a standard preoperative procedure in the preoperative management. If invasion of the adjacent bone occurs, total removal is nearly impossible. Malignant transformation is rare.

The probability of tumor recurrence or growth after surgical resection can be estimated by the tumor's WHO Grade and by the extent of surgery by the Simpson Criteria.

Radiation therapy
Radiation therapy may include photon beam or proton beam treatment, or fractionated external beam radiation. Radiosurgery can be used in lieu of surgery in small tumors located away from critical structures. Fractionated external beam radiation can also be used as primary treatment for tumors that are surgically unresectable, or for patients who are inoperable for medical reasons.

Radiation therapy is often considered for WHO Grade I meningiomas after subtotal (incomplete) tumor resections. The clinical decision to irradiate after a subtotal resection is somewhat controversial, as no class I randomized controlled trials exist on the subject. Numerous retrospective studies, however, have strongly suggested the addition of postoperative radiation to incomplete resections improves both progression free survival (i.e. prevents tumor recurrence) and improves overall survival.

In the case of a Grade III meningioma, the current standard of care involves postoperative radiation treatment regardless of the degree of surgical resection. This is due to the proportionally higher rate of local recurrence for these higher grade tumors. Grade II tumors can behave variably and there is no standard of whether to give radiotherapy following a gross total resection. Subtotally resected grade II tumors should be radiated.

Conventional chemotherapy
Current chemotherapies are likely not effective. Antiprogestin agents have been used, but with variable results. Recent evidence that hydroxyurea has the capacity to shrink unresectable or recurrent meningiomas is being further evaluated.