Approach to the meningioma patient

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.

• 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%.

• 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%.

• 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. ^,

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.