The meningioma is the neurosurgeon's "friend" and often his most enduring challenge. For both the physician and patient, this tumor carries a true tag of benign. It also carries the possibility of "cure" in approximately 80% of cases. Thus, the long-term outcome for a patient with this tumor is a direct function of the skill and assiduousness of the surgeon who removes it.
Elsewhere in the Brain Surgery Information Center's Primer on Brain Tumor Biology, it was mentioned that "benign" often does not really mean benign. Be assured that in this case, the tumor really is benign.
As mentioned earlier in the Primer, each type of brain tumor arises from a specific cell type. The cell of origin for the meningioma is call the arachnoid cap cell, found on the surface coverings (called meninges) of the brain in the paccionian granulations. These serve as the one-way valve system between the water system of the brain and the veins that drain from the brain to the heart.
Interestingly, these tumors have an embryologic relationship with cells found in the muscle layer of the utereus . In fact, it is exceedingly difficult for the pathologist to distinguish the meningioma from the fibroid tumors of the utereus under the microscope. Also, they share the characteristic female hormonal receptors (estrogen and progesterone) on their cell surfaces. This characteristic has lead to the testing of anti-estrogen receptor agents, such as tamoxifin, as a growth-inhibiting agent in these tumors. Clinical studies to date have failed to provide siginificantly positive results.
The following are the main points about optic nerve meningioma:
orbital and optic nerve sheath meningioma are less common than intracranial meningioma. Orbital meningioma often arises secondarily from either intracranial meningioma or optic nerve sheath meningioma.
it is commoner in middle-aged female.
there is a small increased incidence in neurofibromatosis type I
clinical signs of optic nerve meningioma include unilateral papilloedema, optic atrophy and optico-ciliary shunt
there are a variety of histological patterns but within the orbit only two are commonly found (see pictures below for description):
meningotheliomatous
Meningotheliomatous type of meningioma. This is the most common cell type
seen in all meningioma. The tumour has large, ill-defined cells with abundant
cytoplasm. Numerous whorls are formed by several flattened cells wrapped
around a large round cell. Psammomas bodies sometimes occur within the whorls.
psammomatous
This is a variant characterized by the abundance of psammoma bodies.These can
form confluent masses between which lie islands of meningothelial or fibroblastic
-like cells. This is seen less commonly than meningotheliomatous type.
Background: Coined by Harvey Cushing, the term meningioma refers to a set of tumors that arise contiguously to the meninges.
Pathophysiology: Meningiomas may occur intracranially or within the spinal canal. They are thought to arise from arachnoidal cap cells, which reside in the arachnoid layer covering the surface of the brain.
Meningiomas commonly are found at the surface of the brain, either over the convexity or at the skull base. In rare cases, meningiomas occur in an intraventricular or intraosseous location. The problem of classifying meningioma is that arachnoidal cells may express both mesenchymal and epithelial characteristics. Other mesodermal structures also may give rise to similar tumors (eg, hemangiopericytomas or sarcomas). The classification of all of these tumors together is controversial. The current trend is to separate unequivocal meningiomas from other less well-defined neoplasms. Undoubtedly, advances in molecular biology will allow scientists to determine the exact genomic aberration responsible for each specific neoplasm.
Frequency:
In the US: The annual incidence of symptomatic meningiomas is approximately 2 per 100,000 individuals. Meningiomas account for approximately 20% of all primary intracranial neoplasms. However, the true prevalence is likely higher than this because autopsy studies reveal that 2.3% of individuals have undiagnosed asymptomatic meningiomas. Meningiomas are multiple in 5-40% of cases, particularly when they associated with neurofibromatosis-2 (NF-2). Familial meningiomas are rare unless associated with NF-2.
Internationally: The frequency of meningiomas in Africa is nearly 30% of all primary intracranial tumors.
Mortality/Morbidity: Mortality and morbidity rates for meningiomas are difficult to assess. Some meningiomas are discovered fortuitously when CT or MRI is done to assess for unrelated diseases or conditions. Therefore, some patients die with meningioma and not from it.
Meningiomas usually grow slowly, and they may produce severe morbidity before causing death
Factors that may be predictive of a high postoperative morbidity rate include patient-related factors (eg, advanced age, comorbid states such as diabetes or coronary artery disease, preoperative neurological status), tumor factors (eg, location, size, consistency, vascularity, vascular or neural involvement), previous surgery, or previous radiation therapy.
Race: Meningiomas are more prevalent in Africa than in North America or Europe. In Los Angeles county, meningioma is reported more commonly in African Americans than in others.
Sex: Meningiomas afflict women more often than men. The male-to-female ratio ranges from 1:1.4 to 1:2.8.
The female preponderance may be less pronounced in the black population than in other groups.
Meningiomas are equally distributed between boys and girls.
Age: The incidence increases with age.
Meningiomas produce their symptoms by several mechanisms. They may cause symptoms by irritating the underlying cortex, compressing the brain or the cranial nerves, producing hyperostosis and/or invading the overlying soft tissues, or inducing vascular injuries to the brain. The signs and symptoms secondary to meningiomas may appear or become exacerbated during pregnancy but usually abate or improve in the postpartum period.
Irritation: By irritating the underlying cortex, meningiomas can cause seizures. New-onset seizures in adults justify neuroimaging (eg, MRI) to exclude the possibility of an intracranial neoplasm.
Compression: Localized or nonspecific headaches are common. Compression of the underlying brain can give rise to focal or more generalized cerebral dysfunction, as evinced by focal weakness, dysphasia, apathy, and/or somnolence.
Stereotypic symptoms: Meningiomas in specific locations may give rise to the stereotyped symptoms listed in the Table. These stereotypical symptoms are not pathognomonic of meningiomas in these locations; they may occur with other conditions or lesions. Conversely, meningiomas in these locations may remain asymptomatic or produce other unlisted symptoms.
Table 1. Symptoms and Signs Associated with Meningiomas in Specific Locations
Location Symptoms
Parasagittal Monoparesis of the contralateral leg
Subfrontal Change in mentation, apathy or disinhibited behavior, urinary incontinence
Olfactory groove Anosmia with possible ipsilateral optic atrophy and contralateral papilledema (this triad termed Kennedy-Foster syndrome)
Cavernous sinus Multiple cranial nerve deficits (II, III, IV, V, VI), leading to decreased vision and diplopia with associated facial numbness
Occipital lobe Contralateral hemianopsia
Cerebellopontine angle Decreased hearing with possible facial weakness and facial numbness
Spinal cord Localized spinal pain, Brown-Sequard (hemispinal cord) syndrome
Optic nerve Exophthalmos, monocular loss of vision or blindness, ipsilateral dilated pupil that does not react to direct light stimulation but might contract on consensual light stimulation; often, monocular optic nerve swelling with optociliary shunt vessels
Sphenoid wing Seizures; multiple cranial nerve palsies if the superior orbital fissure involved
Tentorial May protrude within supratentorial and infratentorial compartments, producing symptoms by compressing specific structures within these 2 compartments
Foramen magnum Paraparesis, sphincteric troubles, tongue atrophy associated with fasciculation
Vascular: This presentation, although rare, should be considered. Meningiomas of the skull base may narrow and even occlude important cerebral arteries, possibly presenting either as transient ischemic attack (TIA)–like episodes or as stroke.
Miscellaneous
Intraventricular meningiomas may present with obstructive hydrocephalus.
Meningiomas in the vicinity of the sella turcica may produce panhypopituitarism.
Meningiomas that compress the visual pathways produce various visual field defects, depending on their location.
Physical: The physical findings mirror the aforementioned symptoms and include signs due to raised intracranial pressure, involvement of cranial nerves, compression of the underlying parenchyma, and involvement of bone and subcutaneous tissues by the meningioma.
Raised intracranial pressure leads to papilledema, decreased mentation and, ultimately, to brain herniation.
Involvement of the cranial nerves may lead to anosmia, visual field defects, optic atrophy, diplopia, decreased facial sensation, facial paresis, decreased hearing, deviation of the uvula, and hemiatrophy of the tongue.
Compression of the underlying parenchyma may give rise to pyramidal signs that are exemplified by pronator drift, hyperreflexia, positive Hoffman sign, and presence of the Babinski sign. Parietal-lobe syndrome may occur if the parietal lobes are compressed.
Compression of the dominant (usually left) parietal lobe may give rise to Gerstmann syndrome: agraphia, acalculia, right-left disorientation, and finger agnosia.
Compression of the nondominant (usually right) parietal lobe leads to tactile and visual extinction and neglect of the contralateral side.
Compression of the occipital lobes leads to a congruent homonymous hemianopsia.
Spinal meningiomas may give rise to a Brown-Sequard syndrome (ie, contralateral decreased pain sensation, ipsilateral weakness, decrease in position sense), sphincteric weakness and, ultimately, complete quadriparesis or paraparesis.
Causes:
Trauma and viruses have been investigated as possible causative agents for development of meningiomas. However, no definitive proof has yet been found.
On the other hand, the role of radiation in the genesis of meningiomas has been shown.
Patients subjected to low-dose irradiation for tinea capitis may develop multiple meningiomas decades later in the field of irradiation.
High-dose cranial irradiation may induce meningiomas after a short latency period.
Genetic causes have been implicated in the development of meningiomas.
The best characterized and most common genetic alteration is the loss of the NF-2 gene (NF2) on chromosome 22q. NF2 encodes a tumor suppressor known as merlin (or schwannomin).
Of interest, the meningioma locus is close to but probably different from the gene responsible for NF-2.
Up to 60% of sporadic meningiomas were found to harbor NF2 mutations.
Other cytogenetic alterations are chromosomal loss of 1p, 3p, 6q, and 14q.
Loss of chromosome 10 is associated with increased tumor grade, shortened time to recurrence, and shortened survival.
Progression to anaplastic meningioma has been associated with involvement of chromosomal site 17q.
The following events were found to be associated with higher grades of meningiomas: loss of the tumor suppressor in lung cancer-1 gene (TSLC-1), loss of progesterone receptors, increased expression of cyclooxygenase 2 and ornithine decarboxylase.
Monosomy of chromosome 7 is a rare cytogenetic change. However, it is frequently reported in radiation-induced meningiomas.
The invasive potential of meningioma cells seems to be reflected by a balance between the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs).
The most consistent chromosomal abnormality isolated in meningiomas is on the long arm of chromosome 22.
A meningioma is a type of tumor that develops from the meninges, the membrane that surrounds the brain and spinal cord. There are three layers of meninges, called the dura mater, arachnoid and pia mater. Most meningiomas (90%) are categorized as benign tumors, with the remaining 10% being atypical or malignant. However, the word "benign" can be misleading in this case, as when benign tumors grow and constrict and affect the brain, they can cause disability and even be life threatening.
In many cases, benign meningiomas grow slowly. This means that depending upon where it is located, a meningioma may reach a relatively large size before it causes symptoms. Other meningiomas grow more rapidly, or have sudden growth spurts. There is no way to predict the rate of growth for a meningioma, or to know for certain how long a specific tumor was growing before diagnosis.
Most people with a meningioma will only have a tumor at only one site, but it is also possible to have several tumors growing simultaneously in different parts of the brain and spinal cord. When multiple meningiomas occur, more than one type of treatment may have to be used.
Meningiomas vary in their symptoms and appropriate treatment options depending on where they are located.
A primary brain tumor originates in the central nervous system, while metastatic brain tumors spread to the brain from other parts of the body. Meningiomas account for about 27% of primary brain tumors, making them the most common of that type.
Who is at risk?
Meningiomas are most common in people between the ages of 40 and 70. They are more common in women than in men. Among middle-aged patients, there is a marked female bias, with a female: male ratio of almost 3:1 in the brain and up to 6:1 in the spinal cord. Meningiomas are very rare in children, with pediatric cases accounting for only 1.5% of the total.
How is the diagnosis made?
Meningiomas may cause seizures, headaches, and focal neurological defects, such as arm or leg weakness, or vision loss. Patients often have subtle symptoms for a long period before the meningioma is diagnosed. Sometimes memory loss, carelessness, and unsteadiness are the only symptoms.
Diagnosis is made by a contrast enhanced CT and/or MRI (magnetic resonance imaging) scan. While MRIs are in some ways superior, the CT can be helpful in determining if the tumor invades the bone, or if it’s becoming hard like bone.
For more information about CT scans, click here.
For information about MRI, click here.
How are meningiomas classified?
Meningiomas were originally classified into 9 major subtypes based on their structure and form. However, more recently it’s become more common to group them into three major classes, or not to distinguish subtypes at all. Multiple classifications exist today, but the most commonly used is the World Health Organization’s (WHO) "Classification of Tumours of the Nervous System," most recently updated in 2000. The WHO 2000 Classification of Meningiomas is located here.
What difference does the location of the tumor make?
Convexity meningiomas
These grow on the surface of the brain, often toward the front. They may not produce symptoms until they reach a large size. Symptoms of a convexity meningioma are seizures, focal neurological deficits, or headaches.
Falx and Parasagittal meningiomas
The falx is a groove that runs between the two sides of the brain (front to back), and contains a large blood vessel (sagittal sinus). Parasagittal tumors lie near or close to the falx. Because of the danger of puncturing the blood vessels, removing a tumor in the falx or parasagittal region can be difficult. Large parasagittal meningiomas may result in bilateral leg weakness.
Olfactory groove meningiomas
Olfactory groove meningiomas grow along the nerves that run between the brain and the nose. These nerves allow you to smell, and so often tumors growing here cause loss of smell. If they grow large enough, olfactory groove meningiomas can also compress the nerves to the eyes, causing visual symptoms. Similarly, meningiomas growing on the optic nerve can cause visual problems, including loss of patches within your field of vision, or even blindness. They can grow to a large size prior to being diagnosed due to changes in the sense of smell and mental status changes being difficult to catch.
Sphenoid meningiomas
Sphenoid meningiomas lie behind the eyes. These tumors can cause visual problems, loss of sensation in the face, or facial numbness. Tumors in this location can sometimes involve the blood sources of the brain (e.g. cavernous sinus, or carotid arteries), making them difficult or impossible to completely remove.
Posterior fossa meningiomas
Posterior fossa tumors lie on the underside of the brain. These tumors can compress the cranial nerves causing facial symptoms or loss of hearing. Petroclival tumors can compress the trigeminal nerve, resulting in sharp pain in the face (trigeminal neuralgia) or spasms of the facial muscles. Tentorial meningiomas or those near the area where your spinal cord connects to your brain (foramen magnum) can cause headaches, or other signs of brain stem compression like trouble walking.
Intraventricular meningiomas
Intraventricular meningiomas are associated with the connected chambers of fluid that circulate throughout the central nervous system. They can block the flow of this fluid causing pressure to build up, which can produce headaches and dizziness.
Intraorbital meningiomas
Intraorbital meningiomas grow around the eye sockets of your skull and can cause pressure in the eyes to build up, giving a bulging appearance. They can also cause an increasing loss of vision.
Spinal meningiomas
Spinal meningiomas account for less than 10% of meningiomas. They tend to occur in women (with a female/ male ratio of 5:1), usually between the ages of 40 and 70. They are intradural (within or enclosed within the dura mater), extramedullary (outside or unrelated to any medulla) tumors occurring predominantly in the thoracic spine. They can cause back pain, or pain in the limbs from compression of the nerves where they run into the spinal cord.
The only known predisposing factors associated with meningiomas are exposure to radiation, and certain genetic disorders (e.g. neurofibromatosis). Some have reported an association between meningiomas and the site of a previous injury (e.g. head trauma). However, the relationship with previous head injury isn’t well understood. Some have suggested that viruses may play some role as well, but this is unsubstantiated at this point.
Meningiomas are also more common in women than in men, and have shown increased growth during pregnancy. They have hormone receptors and progesterone and estrogen may play a role in their development, but that role is still unclear.
Previous Trauma
Meningiomas have been found at the site of previous trauma (such as near a previous skull fracture, scarred dura, or around foreign bodies), but the relationship isn’t fully understood.
Radiation
Exposure to radiation has been found to be associated with a higher incidence of meningiomas. For example, survivors of Hiroshima have an increased incidence of these tumors. The more recently developed methods of delivering radiation therapy that use focused beams help to limit unnecessary exposure to areas outside the target, and so are expected to be safer. Patients who have undergone broad radiation treatments in the past should take care to watch for symptoms and monitor themselves for meningiomas. Meningiomas caused by radiation exposure are generally more aggressive.
Genetic Predisposition
People with a genetic disorder known as neurofibromatosis type 2 (Nf2) are more likely to develop meningiomas. Of people with malignant meningiomas, a higher percent have mutations in NF2.
There are some genes that may act as tumor suppressors, and the lack or deletion of these genes may make people more susceptible to tumors. For example, patients with Nf2 are, unfortunately, more likely to develop meningiomas because they have inherited a gene which has the potential to cause normal cells to become cancerous.
Viruses
There is a possibility that viruses may be related to meningioma formation, but the relationship is not defined.
What are the indicators of a good or less good outcome?
Age
The age of the patient at the time the tumor is removed influences outcome. Younger patients tend to do better after surgery than older patients do do. However, older patients in otherwise good health should not assume that their chances of a good outcome are diminished.
Tumor location and accessibility
People with tumors that invade the brain tend to do more poorly than patients with tumors that do not invade. Similarly, people with tumors on the outer surface of the brain (convexity) tend to better than those with tumors that are difficult to access, like those on the undersurface of the brain, in regions adjacent to important structures like those needed for breathing or movement, or near large blood vessels. Incomplete removal of the tumor, which is usually due to limitations caused by the location of the tumor, is associated with a higher chance of tumor recurrence. Residual tumor cells are a potential source of new tumor growth.
Extent of removal
The major clinical factor in recurrence is the extent of resection/ removal. How completely the surgeon is able to remove the tumor is highly effected by the location of the tumor, whether it is adjacent or attached to anything else, and the age of the patient.
Survival estimates show a marked difference when grouped by type. Atypical meningiomas have the highest survival rate, followed by benign and then malignant.
Age at the time of diagnosis is also indicates an increased chance of survival. The younger patients have better survival rates.
Brain invasion indicates an increased chance of recurrence. Brain-invasive benign meningiomas act like atypical meningiomas overall.
|
Topic Tags: 
. In fact, it is exceedingly difficult for the pathologist to distinguish the meningioma from the fibroid tumors of the utereus under the microscope. Also, they share the characteristic female hormonal receptors (estrogen and progesterone) on their cell surfaces. This characteristic has lead to the testing of anti-estrogen receptor agents, such as tamoxifin, as a growth-inhibiting agent in these tumors. 
