In 1614, Felix Plater first described meningiomas at an autopsy. In 1938, Harvey Cushing introduced them as a separate category of extraparenchymal tumors.[1] Meningiomas are believed to arise from arachnoid cap cells, and they usually are attached to the dura. These tumors may arise from any location where meninges exist (eg, nasal cavity, paranasal sinuses, middle ear, mediastinum).
In children, the more common locations of meningiomas include the orbit, the temporal region, the foramen magnum, the tentorial region, the subfrontal base, the sellar region, and the ethmoidal air sinus. Such locations for meningiomas are rare in adults. Histologically, the meningothelial type is seen most frequently. As compared to adults, the tumors in children tend to be more aggressive in terms of growth rate, tumor size, propensity to undergo malignant changes, and recurrence rate.
The term optic nerve sheath meningioma (ONSM) does not indicate a definite site of origin. ONSM may be either primary or secondary. Primary ONSMs arise from the cap cells of the arachnoid surrounding the intraorbital or, less frequently, the intracanalicular optic nerve. Secondary ONSM are extensions of intracranial meningioma into the orbit. Secondary ONSMs are much more common than primary ONSMs, but the unqualified term "optic nerve sheath meningioma" ordinarily refers to primary ONSM.
Another rare group of meningiomas consists of tumors that arise from ectopic arachnoid cells within the orbital cavity, either in the muscle cone or in the walls of the orbit. These ectopic, extradural meningiomas do not appear to have a connection to the optic nerve sheath or the optic canal and do not appear to originate intracranially. They probably arise from congenitally displaced nests of meningothelial cells along the orbital wall or within the muscle cone.
United States
The frequency of meningiomas has been the topic of relatively few reports. Hospital-based brain tumor series indicate that the incidence is approximately 20% of all intracranial tumors; population-based studies indicate an overall incidence of 2.3 cases per 100,000.
International
Meningiomas account for approximately 13-19% of all intracranial tumors.
In one series by Coke et al, the overall survival rate for all patients at 5 years and 10 years were 87% and 58%, respectively.[2]
Variability has been shown in the prevalence of meningiomas among Caucasians, Africans, African Americans, and Asians. A greater incidence among Africans than among Caucasians exists.
Although intracranial tumors as a whole show a higher prevalence in males than in females, meningiomas have a 2:1 female-to-male ratio in Caucasians.
In one series of 517 patients with meningiomas at Brigham and Women's Hospital, the female-to-male ratio was 24:1.
In children, the male-to-female ratio is 2:1, with an average age at presentation of 10.1 years (range, 1-16 y).
In Africans, an equal gender ratio is evident.
The incidence of meningiomas increases with age, 2-7 cases per 100,000 in women and 1-5 cases per 100,000 in men. Peak incidence is in the seventh decade in women and in the eighth decade in men.[3, 4]
Meningiomas rarely occur in infants.
Meningiomas rarely occur in children[4] and differ from those in adults and other childhood tumors. Incidence in children is estimated to be approximately 2%. In one retrospective series at the King Faisal Hospital from 1980-1993 that included a total of 318 patients with meningiomas, only 2.8% of patients were children aged 16 years or younger. Meningiomas made up only 2.2% of all CNS tumors seen in children.
In one series by Sheikh et al, the mean age of juvenile cases was 8 years and the mean age for adults was 50 years.[5] Mean ages reported in other series range from 31.7-43 years. The male-to-female ratio is 27:29, adding together all series. Neurofibromatosis occurs in 4.2-16% of cases.
The characteristic profile of a compressive optic neuropathy, such as that caused by ONSM, is usually painless, chronic progressive visual loss that may be accompanied by proptosis.
Transient visual obscurations also have been reported; however, this phenomenon is not a specific feature, as it has been observed in patients with optic disc swelling resulting from other causes.
Age of presentation varies widely, ranging from 3-76 years across all series. In several series, the incidence of visual loss as the presenting feature was more common than proptosis, even though in some series with more ophthalmologic detail, the presentation of proptosis was greater than visual loss. Presentation with either symptom complex is about equal.
Cases may be bilateral (approximately 6%).
An important macroscopic variant of ONSM is the en plaque meningioma (EPM), which is not greatly raised above the level of dura mater. This type of meningioma grows within the meningeal sheath and expands the meninges without forming large exophytic masses. It is prone to invade adjacent bone with accompanying hyperostosis. This group of meningiomas essentially infiltrates the brain and the orbit, mainly via natural apertures (eg, foramina, fissures) and through the passageway of perforating blood vessels, which are increased in number.
Hyperostosis is present in 44% of cases, but it is not a specific finding. EPM typically occurs at the base of the skull, especially within the sphenoid ridge. Clinical presentation depends on the site or extent of the tumor. Patients with juxtaorbital EPM often present with visual complaints. In a series in 1982, Pompili et al reported 33 of 49 cases of EPMs in a series of hyperostosis meningiomas of the sphenoid ridge.[6] Clinical symptoms were not different between the various histopathological types (ie, no difference was seen clinically between EPM and the globular type of hyperostosis meningiomas of the sphenoid).
Common symptoms include the following:
Common neurologic complaints include the following:
Hyperostosis and/or endostosis are common with meningiomas. Hyperostotic meningiomas are viewed as disease of the bone. Globular meningiomas, which are associated with bony reaction and invasion, are referred to as en masse (global) meningiomas.
The presentation of optic nerve sheath meningioma (ONSMs) largely depends on whether they arise from the orbit, within the optic canal, or intracranially. Notwithstanding, the classic triad of ONSM is visual loss, optic atrophy, and optociliary shunt vessels.
The characteristic symptom and sign of ONSM is very slow visual loss with preservation of the central visual field for years.
The presence of an optociliary venous shunt on the disc,[7] if associated with disc pallor or visual loss, is suggestive but not pathognomonic of ONSM. These vessels are more appropriately termed retinochoroid venous collaterals and arise from chronic compression of the central retinal vein. These blood vessels shunt blood into choroidal venous circulation. Optociliary shunts result from meningiomas arising from the optic nerve sheath or from spheno-orbital meningiomas. They can occur with other types of tumors (eg, optic nerve gliomas) and chronic papilledema, but they occur most frequently from old central retinal vein occlusion.
Optic disc pallor and swelling have been reported equally in different series. If there is disc edema, the tumor is at least partially intraorbital.
Disturbance of ocular motility was mainly reported by Sibony et al in one series of 47 patients.[8]
A common etiology for meningiomas is radiation exposure in the range of 132-315 roentgens, which is equivalent to the rad dose of 1-3 Gy. Characteristics of radiation-induced meningiomas include an average latent period of 36-38 years for patients who were exposed to low-dose radiation to the head, whereas patients who develop meningiomas after exposure to high-dose radiation may show signs as early as 5 years postradiation.[9]
In general, radiation-induced meningiomas occur more frequently over the convexities (ie, in about 80% of cases). They have a more frequent recurrence rate, and they exhibit malignant behavior that is also indicated histologically by hypercellularity and pleomorphism.
Head trauma used to be considered a possible risk factor, but recent large studies do not support this association.
Another factor that has been studied is hereditary predisposition.
Loss of DNA on chromosome 22 has been shown in 40% of meningiomas.
In cytogenetic studies, genetic abnormalities at the level of chromosome 22 are seen frequently in meningiomas with the loss of a copy of chromosome 22 as the most commonly reported abnormality.
Monosomy of chromosome 22 has been reported to occur in 70-80% of meningiomas.
Abnormalities of chromosome 22 have been associated with type II neurofibromatosis.
Hormonal factors, such as estrogen and progesterone, have been studied extensively as risk factors for meningiomas because of the striking predominance of meningiomas in women. Other evidence to substantiate the implication of gender-specific hormones comes from data showing increased growth of meningiomas during pregnancy and size changes with menses. Initially, interest was focused on estrogen because it had been reported in one comprehensive review by McCutcheon that 30% of meningiomas have estrogen receptors; however, no further studies were conducted, and interest became focused on other hormones (ie, progesterone).[10]
The progesterone receptor is the most likely candidate as an etiology for meningiomas. Progesterone receptors have been shown to be expressed in 81% of women and in 40% of men with meningiomas. Other studies indicate that progesterone binds to meningiomas in 50-100% of tested specimens; however, most reports show binding in the higher end of this range. No relation has been found between progesterone receptor status and age, sex, tumor location, or menopausal state. These findings have prompted researchers to develop antiprogesterone medications, such as mifepristone (RU-486), which appear to inhibit tumor growth in vitro and in vivo.
Androgen receptors have been found in 40-100% of meningiomas studied in several studies, but their receptor expression is variable, making them less likely candidates in the pathophysiology of meningiomas. Meningiomas vary in expression of receptors for other hormones (eg, epidermal growth factor [EGF], platelet derived growth factor [PDGF], fibroblast growth factor), which makes them less likely candidates for oncogenesis of meningiomas. It has been suggested that the direct stimulatory effect of EGF on PDGF or PDGF itself may be partially responsible for angiogenesis and even oncogenesis in meningiomas. PDGF is a particularly attractive candidate because it has structural homology with the product of c-sis oncogene on chromosome 22. Infectious agents that have been associated with meningiomas include simian vacuolating virus 40 (SV-40) and adenovirus.
See the list below:
View Image | Meningioma of the orbit. Axial sequence on T1-weighted MRI with gadolinium that shows enhancing lesion of the orbit causing proptosis and en plaque in.... |
View Image | Meningioma of the optic nerve sheath. Coronal section of T1-weighted MRI of the orbits that shows a left orbital mass lesion occupying most of the orb.... |
Historically, the classification of meningiomas has been based upon cell shapes, cell patterns, and cell products. The macroscopic appearance of meningiomas may be hemispheric, bun-shaped, or globular, and they may vary in gross appearance as epithelial or mesenchymal. They usually are attached to the dura and invaginate into adjacent neural structures. Enveloped in a thin capsule derived from the adjacent meninges, they remain extraaxial and are separated easily from the brain or the spinal cord.
According to the World Health Organization (WHO) in 1993, 3 different types of meningiomas exist based on malignant behavior, as follows:
Malignant transformation is rare. Originally, malignancy was seen in anaplastic tumors, but they may arise from any of the meningioma variants or atypical meningiomas. Papillary histopathology is associated with local aggressiveness and increased incidence of late distant metastasis. The papillary type is considered malignant by definition and is encountered more frequently in children.
Earlier classification schemes used the term angioblastic meningioma for what is now considered to be a hemangiopericytoma. This neoplasm is distinctly separate from a meningioma, and it shows extremely high propensity for recurrence and metastasis. Hemangiopericytoma is a sarcoma in the new WHO classification.
Growth type classification of meningiomas according to cell type is as follows:
Many believe that patients with optic nerve sheath meningioma (ONSM) can be observed if there is no evidence of intracranial extension and if there is mild or no vision loss or, in some cases, stable degrees of vision loss.[13]
Radiologic findings help diagnose most cases; therefore, biopsy is unnecessary. Biopsy should be reserved for only rare cases with ambiguous neuroimaging findings because the effects on vision can be catastrophic.
Treatment with primary radiation or radiation following surgical removal has been associated with a better chance of visual improvement.[14, 15, 16]
Conventional radiation therapy is beneficial for patients with recurrent (or incompletely resected) benign meningiomas, and it is recommended for patients with aggressive and malignant meningiomas. Patients with meningiomas are good candidates for radiotherapy because the tumors are extra-axial and are visualized easily on CT scan or MRI. Stereotactic radiation and interstitial brachytherapy are useful in some refractory or recurrent meningiomas.
In the largest, most comprehensive review of patients with meningiomas from 1962-1980 by Mirimanoff et al, only 80 patients out of 225 had residual tumor after debulking.[17] This study suggests that the recurrence rate for patients with full resection of tumor is about 10%, whereas patients with subtotal resection had a recurrence rate of 55% at 10 years and 91% at 15 years.
In another study by Barbaro et al, patients with subtotal resection of benign meningiomas were divided into 2 groups; one group received postoperative radiotherapy, and the other group was only observed.[18] The rate of tumor progression was 60% for the latter group and 32% for the former group. In addition, the time to progression was twice as long for patients who had received radiotherapy. The improved survival rate was associated with higher radiation doses; 93% survival rate for patients having received 52 Gy versus 65% for patients treated with smaller doses.
In a study by Goldsmith et al, the 5-year survival rate was 58% for patients with malignant meningiomas who had received additional radiotherapy. This rate was significantly higher than the survival rate of patients who had only surgery. In this group, only 3.6% had serious complications (eg, blindness, brain necrosis). In another review by Glaholm et al, the 10-year survival rate was 46% for patients who had received radiotherapy alone for treatment of unresectable meningiomas.[19]
One proposed protocol to minimize adverse effects is to deliver fractionated external radiation of 1.8 Gy per day for a total of 54 Gy. For superficial tumors, radiation with a 4-6 MV accelerator or a Cobalt 60 machine is preferred because these parameters spare skin lesions and allow a rapid build-up of radiation dose.
Radiosurgery can be delivered with either a gamma knife or a modified linear accelerator. The gamma knife can deliver multiple small fields with relative ease; therefore, it conforms well to uneven masses. The use of linear accelerators for radiosurgery and stereotactic radiotherapy has resulted in an improved outcome from radiation. In a series of 56 skull base meningiomas by Black, 95% of them were controlled (ie, showed no growth) over a 4-year period.[20]
Chemotherapy is reserved for patients with unresectable, recurrent, or previously irradiated meningiomas. Combination treatment with 5-fluroouracil, folate, and levamisole, or a combination of intra-arterial cisplatin with intravenous doxorubicin, may be beneficial. Other proposed combinations include Adriamycin and dacarbazine or ifosfamide and mesna. Adriamycin is an antibiotic that causes DNA damage. Dacarbazine (DTIC) is an alkalizing agent that inhibits DNA synthesis for a total of 1 year, if the tumor responds, or indefinitely until a response occurs.
In a pilot study with mifepristone by Greenberg et al, a marginal response was seen in a small group of patients (6 out of 24 patients).[21] Another study by Grunberg et al confirmed benefit for a majority of 14 patients.[22]
Interferon alpha is the most frequently advocated immunotherapy and is generally well tolerated. It has been shown to have a growth inhibitory effect in vitro, and isolated reports have indicated a stabilizing response in unresectable benign meningiomas.
The management scheme below has been proposed.
In the absence of visual impairment, follow up with visual function testing, including pupil testing, color vision testing, and perimetry, every 6-12 months and obtain an MRI every 1-2 years.
If visual acuity or the visual field deteriorates, it may be beneficial to treat the patient with radiation to the orbit.
If the eye is blind and the tumor is confined to the orbit, observe the patient. (In some cases, if the eye is completely blind, some advocate surgically resecting the ONSM; the globe sometimes can be left behind.)
If the eye is blind and intracranial extension is present, excise the tumor and the nerve. Possible complications of surgery include visual impairment, postoperative bleeding, and cerebrospinal fluid leakage.
Preoperative evaluation of patients with anterior basal meningiomas includes a careful visual testing and a complete neuro-ophthalmological evaluation. Endocrine testing is important, as pituitary insufficiency has been reported to occur in 22% of patients with anterior skull base meningiomas. MRI angiography may be helpful in establishing the relationship of the tumor to its vascular supply. Three-dimensional scanning is becoming increasingly popular because it can be taken into the operating room and linked to the operative instruments. Surgery remains the mainstay of meningioma management.
For any skull base surgery, the procedure can be divided into 3 steps, as follows:
In cases of optic nerve sheath meningioma (ONSM), a team approach involving ophthalmologists, neurologists, neurosurgeons, radiation therapists, and radiologists is most beneficial.
The use of antihormonal agents in treating meningiomas is in anecdotal reports. Medical treatment is reserved for atypical and malignant meningiomas as an adjunct to surgery, partially resected benign meningiomas, and recurrence of meningiomas after a surgical resection.
Tamoxifen, an antiestrogen hormone, has been reported in a handful of patients with refractory or unresectable meningiomas; in one study by De Monte, the use of this agent resulted in stabilization of 6 out of 9 cases.[23]
Clinical Context: Competitively binds to the estrogen receptor, producing a nuclear complex that decreases DNA synthesis and inhibits estrogen effects.
Clinical Context: Used experimentally in patients with recurrent benign meningiomas; in one study, tumor regression was reported in 5 out of 14 patients.
Outpatient follow-up care of patients with optic nerve sheath meningioma (ONSM) includes visual acuity testing and field testing, in addition to an imaging study in the form of MRI with gadolinium, preferably every year to check for recurrent disease.
Visual loss is the major complication of surgery for ONSM. Surgery is rarely successful unless the ONSM is pedunculated.
In one series by Coke et al, the overall survival rate for all patients at 5 years and 10 years was 87% and 58%, respectively.[2] The 5- and 10-year survival rates for atypical meningiomas were over 85%. For malignant meningiomas, the survival rate is reported to be approximately 60%. All patients in this series had received surgery and high-dose radiation. No difference in survival rate was apparent in patients as a function of dural or cortical invasion. Long-term survival is possible for patients with atypical and malignant meningiomas treated with surgery and postoperative radiation.
In a review from the literature by Black et al, of 417 patients older than 65 years who underwent meningioma surgery, the average 30-day mortality rate was 16%.[24] The complication rate averaged 39%. The series by Milosevic et al included the records of 59 patients who were treated at the Princess Margaret Hospital from 1966-1990 with histologically confirmed intracranial atypical or malignant meningiomas.[25]
Immediately after diagnosis, 24 patients were referred for radiation, and the remainder of the patients was referred after at least 1 recurrence. The extent of the most recent surgery prior to radiation was gross total excision in 17 patients, subtotal excision in 35 patients, biopsy in 3 patients, and none or unknown in 4 patients. All patients received megavoltage radiation to a median dose of 50 Gy.
Disease progressed in 39 patients (66%) after radiation. Of these, 36 patients died of meningioma, and 3 patients were alive after further surgery. The 5-year actuarial overall and cause-specific survivals were 28% and 34%, respectively. Factors that were associated independently with higher cause-specific survival by multivariate analysis include an age younger than 58 years, treatment after 1975, and a radiation dose of 50 Gy or higher. It is recommended that all patients be evaluated for radiotherapy immediately after initial surgery.
Young age, modern imaging and treatment planning techniques, and postoperative radiation dose of at least 50 Gy contribute to improved outcome in patients with atypical or malignant meningiomas.
In a prospective study that compared prognosis in elderly patients (ie, >65 y) to younger patients, Black et al evaluated 114 patients undergoing meningioma resection divided into 2 groups, as follows: 57 patients aged 65-87 years and a control group of 57 patients aged 25-64 years matched by the American Society of Anesthesiology (ASA) status and tumor site.[24]
Operative complications, 30-day mortality, and preoperative and postoperative neurologic status were assessed with follow-up care for 1-3 months. Complication rates in the 2 groups were similar and were low, that is, 7% in the elderly population had a surgical complication compared with 8.8% of younger patients. Excluding asymptomatic deep venous thrombosis (DVT) detected by screening, 3 elderly patients (5.2%) had medical complications compared with 2 control patients (3.5%).
The vast majority of patients (ie, 93% of the elderly group and 89.4% in the control group) experienced either improvement or no change in neurological status at follow-up 1-3 months after surgery.
One death among elderly patients occurred within 30 days, for a mortality rate of 1.8% compared with no mortality in the younger age group. The death was the result of pneumonia 3 weeks after surgery. They attributed the lower morbidity and mortality rates after meningioma surgery in elderly patients to better patient selection and surgical techniques and to better preoperative and postoperative care by health care providers.
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