What Is Meningioma?

Meningioma, also known as meningeal tumor, is typically a slow-growing tumor that forms from the meninges, the membranous layers surrounding the brain and spinal cord.

Symptoms depend on the location and occur as a result of the tumor pressing on nearby tissue. Many cases never produce symptoms. Occasionally seizures, dementia, trouble talking, vision problems, one sided weakness, or loss of bladder control may occur.

Risk factors include exposure to ionizing radiation such as during radiation therapy, a family history of the condition, and neurofibromatosis type 2. As of 2014 they do not appear to be related to cell phone use. They appear to be able to form from a number of different types of cells including arachnoid cells.

If there are no symptoms, periodic observation may be all that is required. Most cases that result in symptoms can be cured by surgery.

Following complete removal less than 20% recur. If surgery is not possible or all the tumor cannot be removed radiosurgery may be helpful. Chemotherapy has not been found to be useful.  A small percentage grow rapidly and are associated with worse outcomes.

Onset is usually in adults. In this group they represent about 30% of brain tumors. Women are affected about twice as often as men. Meningiomas were reported as early as 1614 by Felix Plater.

Symptoms Of Meningioma

Small tumors (e.g., < 2.0 cm) usually are incidental findings at autopsy without having caused symptoms. Larger tumors may cause symptoms, depending on the size and location.

  • Focal seizures may be caused by meningiomas that overlie the cerebrum
  • Tumors of the Sylvian aqueduct 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
  • Diplopia (Double vision) or uneven pupil size may be symptoms if related pressure causes a third and/or sixth nerve palsy

Causes

The causes of meningiomas are not well understood. Most cases are sporadic, appearing randomly, while some are familial.

Persons who have undergone radiation, especially to the scalp, are more at risk for developing meningiomas, as are those who have had a brain injury. Atomic bomb survivors from Hiroshima had a higher than typical frequency of developing meningiomas, with the incidence increasing the closer that they were to the site of the explosion. Dental x-rays are correlated with an increased risk of meningioma, in particular for people who had frequent dental x-rays in the past, when the x-ray dose of a dental x-ray was higher than in the present.

Having excess body fat increases the risk.

A 2012 review found that mobile telephone use was unrelated to meningioma.

People with neurofibromatosis type 2 (NF-2) have a 50% chance of developing one or more meningiomas. Ninety-two percent of meningiomas are benign. Eight percent are either atypical or malignant.

In terms of genetics, the most frequent mutations (~50%) involved in meningiomas are inactivation mutations in the neurofibromatosis 2 gene (merlin) on chromosome 22q.

TRAF7 mutations are present in about one-fourth of meningiomas. Mutations in the TRAF7, KLF4, AKT1, and SMO genes are commonly expressed in benign skull-base meningiomas. Mutations in NF2 are commonly expressed in meningiomas located in the cerebral and cerebellar hemispheres.

Diagnosis

Meningiomas are visualized readily with contrast CT, MRI with gadolinium, and arteriography, all attributed to the fact that meningiomas are extra-axial and vascularized. CSF protein levels are usually found to be elevated when lumbar puncture is used to obtain spinal fluid.

Although the majority of meningiomas are benign, they may have malignant presentations. Classification of meningiomas are based upon the WHO classification system.

  • Benign (Grade I) – (90%) – meningothelial, fibrous, transitional, psammomatous, angioblastic
  • Atypical (Grade II) – (7%) – chordoid, clear cell, atypical (includes brain invasion)
  • Anaplastic/malignant (Grade III) – (2%) – papillary, rhabdoid, anaplastic (most aggressive)

In a 2008 review of the latter two categories, 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.

Malignant anaplastic meningioma is an especially malignant tumor with aggressive behavior. Even if, by general rule, neoplasms of the nervous system (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 meningiomas tend to be connected to blood vessels. Thus, cancerized cells can escape into the bloodstream, which is why meningiomas, when they metastasize, often turn up around the lungs.

Treatment

Many individuals have meningiomas, but remain asymptomatic, so the meningiomas are discovered during an autopsy.

One to two percent of all autopsies reveal meningiomas that were unknown to the individuals during their lifetime, since there were never any symptoms.

Observation

Observation with close imaging follow-up may 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 at an average of 4 mm / year. In this study, younger patients were found to have tumors that were more likely to have grown on repeat imaging; thus are poorer candidates for observation.

In another study, clinical outcomes were compared for 213 patients undergoing surgery vs. 351 patients under watchful observation. Only 6% of the conservatively treated patients developed symptoms later, 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.

Surgery

Meningiomas usually can be surgically resected (removed) and result in a 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. It is rare for benign meningiomas to become malignant.

Radiation Therapy

Radiation therapy may include photon-beam or proton-beam treatment, or fractionated external beam radiation. Radiosurgery may be used in lieu of surgery in small tumors located away from critical structures.

Fractionated external-beam radiation also can be used as primary treatment for tumors that are surgically unresectable or, for patients who are inoperable for medical reasons.

Radiation therapy often is 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 suggested strongly that 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 may 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.

Joung H. Lee
Meningiomas: Diagnosis, Treatment, and Outcome
Springer; 2008 ISBN-13: 978-1848829107

Image: Nephron, CC BY-SA 3.0. Micrograph of a meningioma showing the characteristic whorling.