Introduction
Meningiomas are slow-growing extraaxial tumors that account for about 25% of all intracranial tumors. The World Health Organization (WHO) classifies meningiomas as grade I, II, or III based upon morphologic criteria with higher grades correlating with more aggressive behavior such as local invasion, recurrence, and shortened survival. The main options for the management of meningiomas include surgery, radiation, and observation. The management of these patients varies depending on a combination of clinical factors including the patient’s clinical symptoms, radiographic characteristic of the tumor, grade of the tumor, and extent of prior resections. Grade I meningiomas in asymptomatic patients can typically be managed conservatively with clinical observation and serial imaging. For symptomatic patients or patients with more aggressive tumors, surgical resection with potential adjuvant radiation are favored depending on the grade and extent of resection. Unfortunately, medical therapy for recurrent meningiomas is lacking, although several clinical trials are underway to assess the efficacy of various adjuvant therapies.
The goal of this chapter is to help guide clinicians in providing the best clinical care for patients with meningiomas. Case-based presentations are used to discuss the management approaches to patients presenting with different clinical symptoms and grades of meningiomas. Although general guidelines to the management of these patients are proposed, the decision for treatment should be made on an individualized basis carefully weighing the risks and benefits of each treatment option.
Epidemiology
Meningiomas are extraaxial brain tumors that typically present as slowly growing dural-based masses, most of which (98.2%) are nonmalignant. They are the most common of all primary central nervous system tumors (37.1%) with an incidence rate of 8.33 per 100,000 people. There were 145,916 new cases diagnosed between 2011 and 2015, and 31,990 new cases are projected for 2019 according to the Central Brain Tumor Registry in the United States. The incidence of meningiomas increases significantly with age, as they occur most frequently in adults over the age of 65 and are rare in children ages 0–14. The median age of diagnosis is 66 years. Women are twice as likely to develop meningiomas as men, and thus an etiologic role for hormones in the development of meningiomas has been hypothesized.
The etiology for the majority of meningiomas is unknown. These tumors are often benign, slow-growing, and solitary. However, several potential risk factors have been shown to be associated with the development of meningiomas, including prior exposure to ionizing radiation and particular genetic conditions. Radiation-induced meningiomas are the most common brain neoplasm resulting from ionizing radiation. These meningiomas are clinically and biologically more aggressive than sporadic meningiomas; they have more frequent mitoses, are often atypical and multifocal, and have higher recurrence rates. , In many cases, there can be a latency period of more than 20 years between radiation exposure and meningioma occurance. In terms of genetic predispositions, 50 to 70% of individuals with neurofibromatosis type 2 (NF2), an autosomal dominant disorder characterized by mutations in the NF2 gene, develop one or more meningiomas (see Chapter 16 for further discussion of NF2). This gene is a tumor suppressor gene on chromosome 22 that encodes for the protein merlin, which regulates meningioma cell proliferation and tumor formation. Meningiomas arising from this condition are phenotypically more aggressive and develop earlier in life than their sporadic counterparts. The other broad class of genetically-driven meningiomas consists of those with mutations in other genes such as Smoothened (SMO) , TRAF7 , AKT1, and PI3KA . No genetic alterations are detected in 20% of meningiomas. In these meningiomas, epigenomic mutations may play a crucial role in tumor formation.
Meningiomas arise from neoplastic arachnoid cap cells in the meningeal coverings of the brain and spinal cord. They can arise anywhere along the dura and are commonly found in the parasagittal and convexity regions. They may also arise in the skull base or at sites of dural reflection, including the falx cerebri, tentorium cerebelli, and venous sinuses. Meningiomas arising from the cerebral meninges account for 79.8%, and 4.2% arise from the spinal meninges. Spinal meningiomas are most often found in the thoracic spine, followed by the cervical spine and the craniocervical junction. They may also arise in the optic nerve sheath and choroid plexus, but these locations are less common.
Clinical presentation
Many meningiomas are asymptomatic and are discovered incidentally during neuroimaging for unrelated symptoms or at autopsy. One study showed that meningiomas are found in about 1% of brain magnetic resonance imaging (MRI) scans of the general adult population (ages 45 to 97). Many meningiomas remain the same size or grow very slowly over a long period of time without the patient noticing symptoms. These incidentally discovered tumors are usually treated conservatively with observation rather than surgical intervention. However, meningiomas may become symptomatic due to compression of nearby brain structures, blockage of cerebrospinal fluid (CSF) flow and venous sinuses, or even invasion into brain tissue. About 30% of patients with intracranial meningiomas present with seizures, but the pathogenesis of this is poorly understood.
Symptomatic focal deficits are linked to the tumor location. As the tumors grow at a slow rate, symptom onset is typically gradual, and patients often do not notice these changes immediately. Patients may experience visual changes with tumors disrupting the optic pathway. Cerebellopontine angle meningiomas can lead to cranial nerve deficits including hearing loss and facial pain. Olfactory groove or sphenoid ridge meningiomas can compress the olfactory tract and interfere with smell. Large subfrontal meningiomas can cause behavioral changes such as inattention and apathy. Meningiomas in proximity to the motor strip can lead to focal weakness. In addition to symptoms caused by direct compression of adjacent neural structures, meningiomas can also cause symptoms related to increased intracranial pressure or obstruction of the ventricular system leading to obstructive hydrocephalus. These patients can present with headaches, gait difficulties, and even mental status deterioration.
Classification
Meningiomas are usually lobular, well-circumscribed masses. Tumors that grow diffusely over the dura are referred to as meningioma en plaque . Although they often appear similar on imaging and macroscopically, meningiomas can exhibit heterogeneity on histopathology. The WHO classifies meningiomas into three groups based upon morphologic criteria (see Chapter 1 , Case 1.5 for further discussion of histologic classification of meningioma). These classifications have been shown to correlate with clinical outcomes. Most meningiomas are WHO grade I and carry an excellent prognosis, whereas rarer WHO grade II and III meningiomas are more likely to be invasive, recur locally following treatment, and have shorten overall survival. Due to these factors, treatment planning favors more aggressive approaches with increasing WHO grade. The characteristics of each grade of meningioma are summarized below.
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WHO grade I: Account for 80.6% of meningiomas. They are benign and subdivided into nine subtypes, including meningothelial, fibrous (fibroblastic), transitional (mixed), psammomatous, angiomatous, microcystic, lymphoplasmacyte-rich, metaplastic, and secretory. Their histology includes occasional mitotic figures. The rate of recurrence is 7–25%.
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WHO grade II: Account for 17.6% of meningiomas. They include atypical, clear-cell, and choroid meningiomas. In contrast to grade I meningiomas, grade II tumors have histologic features including more mitotic activity (4 or more mitoses per 10 high-powered fields), brain invasion, or three or more of the following: prominent nucleoli, increased cellularity, small cells with high nuclear-to-cytoplasmic ratio, sheet-like growth, and localized spontaneous necrosis. The rate of recurrence is 29–59%.
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WHO grade III: Account for 1.7% of meningiomas. These tumors are malignant and include papillary, anaplastic, and rhabdoid meningiomas. Histologic features of these meningiomas include significantly increased mitotic activity (20 or more mitoses per 10 high-powered fields), loss of typical growth patterns, infiltration of the brain, atypical mitoses, and multifocal spontaneous necrosis. The rate of recurrence is very high at 60–94%.
Nonmalignant meningiomas have a 5-year survival rate of 86.7% and a 10-year survival rate of 81.5% for all ages, and malignant meningiomas have a 5-year survival rate of 63.8% and a 10-year survival rate of 56.1% for all ages.
Due to their slow growth rate and a majority of tumors being asymptomatic, incidental meningiomas can be managed conservatively with observation and serial imaging. For most cases of symptomatic meningioma, surgical resection is the preferred treatment. The 5-tier Simpson scale grades the extent of surgical resection and strongly correlates with risk of meningioma recurrence ( Table 10.1 ). The dural tail is the site of thickening and enhancement of the dura is seen adjacent to meningiomas. Whereas evidence on whether the dural tail harbors neoplastic cells continues to be controversial, with some studies suggesting that it is an imaging correlate of dilated meningeal vessels, many still advocate for the removal of the dural tail during surgery, as it has been shown to affect the timing of tumor recurrence. Bone involvement is common and can lead to hyperostosis and osteolysis. Hyperostosis occurs in 20% of cases and varies in appearance unrelated to tumor size. It is often associated with bony invasion of tumor but may also represent a reactive phenomenon. The presence of strong, homogeneous enhancement within hyperostotic bone suggests tumor infiltration. Malignant meningiomas typically invade the brain and can cause osteolysis of the adjacent calvarium with extension into the scalp. , This osteolytic activity results in sequestration of the tumor within bone. Additionally, primary intraosseous meningiomas that cause osteolysis are more likely to behave in a malignant manner and have anaplastic or malignant hisopathology. ,
| Extent of resection | Recurrence risk (10-year interval) | |
|---|---|---|
| Grade I | Macroscopically complete removal of tumor, involved bones, venous sinuses, and dural tail. | 9% |
| Grade II | Macroscopically complete removal of tumor, coagulation of dural tail. | 19% |
| Grade III | Macroscopically complete removal of tumor, no resection of dural tail. | 29% |
| Grade IV | Partial tumor removal, no resection of dural tail. | 44% |
| Grade V | Simple decompression, no resection of dural tail. | 100% |
Imaging characteristics
(Also see Chapter 5 for approach to the imaging of dural-based lesions.) MRI is currently the main diagnostic method of choice in the evaluation of meningiomas. Meningiomas typically appear as an isointense to slightly hypointense unilobular mass relative to grey matter with associated displacement of cortical grey matter on T1-weighted sequences pre-contrast. On post-contrast imaging, meningiomas demonstrate strong homogenous enhancement often seen with a dural tail, a peripheral dural thickening adjacent to the tumor. Areas of necrosis or calcifications within the tumor do not enhance and will give the tumor a patchy, heterogeneous appearance. On T2-weighted images, meningiomas can demonstrate more heterogeneous intensity which may be indicative of particular tumor characteristics. Hyperintensity on T2-weighted images suggests softer tumor texture, whereas hypointensity suggests firmer texture or even calcification. , Hyperintense tumors are often accompanied by increased likelihood and severity of brain edema. This is thought to be due to the elevated water content of these tumors that allows water diffusion into surrounding brain. T2-weighted MRI can also provide an indication to the extent of brain invasion. Extraaxial tumors can exhibit a crescent-shaped cleft of CSF between the mass and brain, although this cleft can be absent in the setting when higher-grade meningiomas invade the brain. An ambiguous brain-tumor border on T2-weighted MRI has been shown to be correlated with a greater degree of tumor proliferation. Magnetic resonance venography (MRV) and magnetic resonance angiogram (MRA) are useful in determining a tumor’s relation to surrounding vasculature. MRV can be used to evaluate the presence of local venous sinus invasion, interrupted blood flow, and the presence of collateral venous drainage. MRA and digital subtraction angiograph (DSA) can aid in identifying the arterial branches supplying the tumor and the extent of tumor vascularization. As meningiomas arise from the dura, arterial blood supply of the tumor is typically from the dural arteries that supply the dura adjacent to the tumor. In the setting of significant tumor vascularization, preoperative embolization of vessels supplying the tumor can significantly reduce blood loss during surgery. Meningiomas may grow near or even be in contact with eloquent regions of the brain, so surgical management of meningioma patients must balance extent of resection with preservation of eloquent function. Functional MRI (fMRI) can be used alongside intraoperative cortical mapping to inform the optimal degree of tumor resection for clinical outcome.
CT images are often less useful in the evaluation of tumor characteristics and relationship to surrounding neural structures and vasculature compared to MRI. However, CT scans can be useful in the evaluation of surrounding bony involvement. In addition to thickening of the adjacent dura, meningiomas can also extend locally into the surrounding bone, with localized hyperostosis or erosion. The effect of the tumor on the bony anatomy is best appreciated on a CT image. Calcifications of the tumor are also more evident on CT scan, shown as patchy areas of hyperdensity within the hypodense tumor.
Common sites of occurrence
Meningiomas can arise from any dura ( Fig. 10.1 ). Common sites of meningiomas are parasagittal ( Fig. 10.2 ) and within the cerebral convexity ( Fig. 10.3 ), with each location accounting for about 20% of meningiomas.
With tumors in proximity to the superior sagittal sinus (SSS), evaluation of the extent of SSS involvement through MRV is critical for management decisions, surgical planning, and developing goals of SSS reconstruction. Sindou classified parasagittal tumors based on the level of SSS involvement and invasion into six types ( Fig. 10.4 ). ,
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Type I: Tumor is attached to the outer surface of the SSS lateral wall.
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Type II: Tumor has invaded the lateral recess.
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Type III: The tumor has invaded the lateral wall.
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Type IV: The tumor has invaded the lateral wall and roof of the SSS.
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Type V: The tumor has invaded the whole SSS except one lateral wall.
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Type VI: The tumor has invaded the whole SSS.
Parasellar meningiomas arise from the tuberculum sellae and clinoid processes and can extend to the planum sphenoidale, olfactory groove, or sphenoid wing ( Fig. 10.5 ). Very rarely, they can arise from the optic chiasm and spread anteriorly to the optic nerves and posteriorly through the optic tracts to the lateral geniculate bodies.
Meningiomas can also occur at other, less common locations, including the tentorium ( Fig. 10.6 ). Tentorial meningiomas account for about 5% of meningiomas and can extend supratentorially or infratentorially ( Fig. 10.6 ). Falcine meningiomas arise from the falx cerebri and account for 5 to 9% of meningiomas. The remaining locations include the greater or lesser sphenoid wing, olfactory groove, and less commonly, the optic nerve sheath, choroid plexus, and spine. In about 1% of cases, meningiomas will arise outside of the dura, in sites including the temporal bone, mandible, mediastinum, and lung.
Clinical cases
Case . An elderly patient presents with 2 years of intermittent sinus headaches without other associated symptoms. The patient has no other significant past medical history or history of other malignancies. Head CT demonstrates a partially calcified parasagittal mass.
Teaching Points: Evaluation and Management of a Parasagittal Meningioma. As with any patient who presents with a new chief complaint, the management of a patient presenting with a new mass suspicious for meningioma begins with a detailed clinical history including the onset, duration, and quality of symptoms. A clinical examination should include a full neurological assessment of mental status, cranial nerve, motor, sensory, and cerebellar function with emphasis on particular neurological systems depending on the location of the mass. Any deficits found on the neurological assessment should be correlated with tumor location, associated peritumoral edema, and vascular involvement.
Signs and symptoms of parasagittal and parafalcine meningiomas depend on their location along the SSS. Tumors arising in the anterior aspect of the falx and SSS often present with symptoms of personality changes and headaches. Meningiomas located along the middle third of the SSS can present with seizures and focal motor or sensory deficits. Masses in the posterior aspect of the falx and SSS can cause visual symptoms and compression of the ventricular system leading to headaches and papilledema. CT is the most common imaging modality to assess any new neurological complaints; therefore, patients often will present with CT findings suspicious for meningioma. An MRI should be obtained to further evaluate the location and characteristics of the tumor, including its relationship to surrounding neural structures, vasculature, and amount of peritumoral edema. An MRI with contrast was obtained for the patient which demonstrated a parasagittal homogenously enhancing mass with minimal surrounding T2 fluid attenuated inversion recovery (FLAIR) signal ( Fig. 10.2 ). MRV demonstrated the tumor abutting the SSS without occlusion ( Fig. 10.2E,F ).
Because of the slow-growing nature of meningiomas, most of these tumors are discovered incidentally and can be observed without surgical intervention. In patients who present with a newly diagnosed mass suspicious for meningioma without prior tissue diagnosis, the management options depend vastly on the patient’s symptoms. In the asymptomatic patient, observation is generally favored, especially in elderly patients (>85 years of age), as with the patient presented in this case. Conservative management consists of surveillance imaging and symptom monitoring. MRI scans are performed at 3-month intervals after initial diagnosis of the tumor. If the tumor demonstrates stable size, then MRI scans can be spaced out to 6 months, then yearly to ensure the tumor remains stable. If the tumor demonstrates evidence of growth, then more frequent imaging is performed, and treatment options are discussed with the patient. Observation is also preferred in younger patients with asymptomatic meningiomas located in non-eloquent regions without peritumoral edema and mass effect. The authors’ practice is to follow patients with serial imaging for life, as the tumor’s growth pattern can change over time. As is the case with this patient, who is above the age of 85 with no prior history of cancer, presenting with an asymptomatic parasagittal meningioma without significant peritumor edema or mass effect, conservative observation with serial imaging was the elected management.
There are cases, however, where surgical intervention may be recommended in asymptomatic patients. A tissue diagnosis through biopsy or resection, if feasible, may be necessary if the diagnosis of meningioma is not certain, such as in patients with history of prior malignancy with concerns for metastatic disease. Additionally, there are certain imaging and clinical characteristics of the tumor that may suggest a more aggressive growth pattern or a higher-grade meningioma. These tumors would prompt early tissue diagnosis to further dictate postoperative adjuvant treatment. Tumors that display significant T2 signal on MRI that lack calcification are more likely to have an aggressive growth pattern. Meningiomas in younger patients that are greater than 3 cm in size are more likely to have continued growth. In young patients with consistent tumor growth over the span of a year or two, surgical resection may be preferred given the natural history of the disease. Surgery at this time may be more beneficial with its smaller size. Furthermore, in tumors with close proximity to vital vascular structures or eloquent regions, early surgical intervention may be preferred to prevent potential invasion into these structures with subsequent growth and to minimize surgical risk.
Clinical Pearls
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The decision for observation or surgery of a meningioma should be made on an individual basis after discussions with the patient, taking into account the patient’s clinical presentation, imaging characteristics, tumor growth patterns, and other medical history and comorbidities.
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In symptomatic patients or patients with rapidly enlarging tumors without tissue diagnosis, surgery is the main treatment modality for both symptomatic relief and pathologic diagnosis.
Case . While on a trip out of state, a middle-aged patient experienced nausea, diarrhea, headaches, and disorientation. Upon arrival at a local hospital, they were noted to have an episode of speech difficulty concerning for seizure activity. CT and MRI scans show a large right frontal extraaxial mass with significant T2 FLAIR intensity and mass effect ( Fig. 10.3 ). The patient also noted an expanding, tender lump on the right side of their forehead over the last year.
Teaching Points: Management of Meningioma of the Convexity. The patient’s physical and neurological examination was normal, with the exception of a bony, tender protrusion on their right forehead. The MRI was most consistent with a right frontal convexity meningioma. In contrast to the MRI findings from the previous patient, this patient’s tumor is significantly larger (>3 cm) with significant peritumoral edema and associated mass effect on the surrounding normal brain. Tumors with significant edema also increase the risk of seizure activity. Given the patient’s relatively young age, large tumor size, significant cerebral edema associated with the tumor, mass effect of the tumor on the adjacent brain, and the fact that they are symptomatic, surgery was recommended for diagnosis, to decrease mass effect, and for symptomatic relief.
Patients who present with seizures should be placed on antiepileptic drug therapy (AED). In patients who have significant peritumoral edema leading to focal neurological deficits or symptoms of increased intracranial pressure, corticosteroids can be administered to decrease cerebral edema prior to surgery. However, many patients with meningioma have very little to no vasogenic edema, even in cases of large tumors. When indicated, dexamethasone can be started on doses up to 16 mg/day divided over four doses and tapered down to a minimal effective dose or discontinued in the postoperative period. The patient was started on levetiracetam and dexamethasone.
Gross total resection (GTR) of tumor is the goal for any surgical resection of meningioma if feasible. The estimated 10-year progression-free survival rates are about 60–80% for GTR of WHO grade I meningiomas and about 50% for those with subtotal resection (STR). Once surgical intervention is decided, further preoperative evaluation of the tumor’s relationship to neighboring structures is needed for safe surgical planning. Given the tumor’s proximity to the anterior cerebral arteries, MRA and CTA were obtained to further evaluate the tumor’s relationship to the vasculature. The patient’s CTA demonstrated that the anterior cerebral arteries were displaced medially by the tumor and showed an incidental right anterior cerebral artery aneurysm ( Fig. 10.3E ). The patient’s MRI further demonstrated enhancement in the subgaleal space and the skull adjacent to the tumor ( Fig. 10.3B ). A CT was performed to better evaluate the extent of bone involvement, which showed osseous infiltration of the tumor ( Fig. 10.3F ). The patient underwent surgical resection of the meningioma and involved calvarium in conjunction with plastic surgery with subsequent cranioplasty. With the advent of modern surgical navigation and techniques, combined with the favorable location of this patient’s frontal convexity meningioma, it was possible to achieve a GTR including the involved dura and bone. Reported surgical complication rates are low for convexity meningiomas between 8–10%. A study found that less than 2% of patients with large (>4 cm) convexity tumors experienced new neurological deficits postoperatively.
The patient’s pathologic diagnosis returned as a WHO grade I meningioma. Grade I meningiomas are the most common and are benign, with a recurrence rate of 7–25%. Aggressiveness and recurrence of WHO grade I meningiomas depends largely on extent of surgical resection and tumor location. The extent of resection, graded on the Simpson Scale, predicts the probability of recurrence and therefore determines treatment course. For grade I meningiomas, the overall tumor recurrence rate for Simpson grades I, II, III, and IV resections are 5%, 22%, 31%, and 35%, respectively. Grade I meningioma resections with Simpson grades I–III (indicating total/near total resection of tumor) generally only require observation with serial MRI scans following surgery as the risk of tumor recurrence is low. Resections with Simpson grades IV–V (indicating partial/minimal resection of tumor) have a higher recurrence rate. In those cases, planning for a combination of STR followed by adjuvant high precision stereotactic radiosurgery (SRS) or intensity modulated radiotherapy can be considered to maximize complete tumor treatment while minimizing the risk of adverse events, especially in tumors in critical areas such as the skull base. Tumors located in the skull base have significantly reduced recurrence-free survival and overall survival likely due to the inability to achieve gross total or near total resection.
In grade I meningiomas that are not conducive to complete surgical resection or near total resection due to high surgical risks to surrounding neural structures, such as those of the skull base, SRS can be used as first-line therapy. SRS consists of extremely precise, high dose per fraction radiotherapy delivered with a 3D localization system in a single session usually to small, well-defined targets (see Chapter 3 , Case 3.2 for stereotactic radiotherapy in neuro-oncology). This option is typically feasible for tumors less than 3–4 cm in diameter that are at least 2 mm away from critical structures such as the optic nerve and chiasm. A retrospective study found a 5-year progression-free survival of 87% for grade I, 56% for grade II, and 47% for grade III meningiomas treated with SRS. Tumors involving the skull base can be challenging to target in one radiosurgery session due to variable contours, ambiguous margins, and proximity to critical structures. Fractionated SRS may be used in these cases to deliver ablative doses over several treatments. Intensity-modulated radiation therapy refers to external beam radiation therapy from distinct beam orientations. This treatment can be optimized to provide a desired dose distribution in the patient.
Following the successful GTR of the meningioma, the patient was followed with surveillance imaging to monitor for tumor recurrence initially at 3-month and 6-month intervals followed by yearly intervals. They remain well with no evidence of tumor recurrence.
Clinical Pearls
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GTR is the goal of any meningioma surgery.
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Extent of resection after meningioma surgery is determined by the Simpson grading scale with Simpson grades I–III indicating total/near total resection of tumor and Simpson grades IV–V indicating partial/minimal resection of tumor.
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For WHO grade I meningiomas, tumors can be monitored with serial imaging after GTR if the patient remains asymptomatic.
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