Meningiomas represent 30% of all primary brain tumors. Anterior skull base meningiomas represent 8.8% of all meningiomas. Surgical resection is a main treatment option for tumors that are symptomatic and/or growing. Recurrence is directly related to the extent of resection of the tumor, the dural attachment, and pathologic bone. Endoscopic endonasal approaches represent an important addition to the treatment armamentarium for skull base meningiomas. This article provides an overview of meningiomas, with a focus on those of the anterior skull base and their management.
Key points
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Meningiomas are mostly benign tumors (∼95%); however, more aggressive and malignant variants exist.
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The rate of recurrence is directly related to the extent of resection of the tumor, its dural attachment, and pathologic bone.
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The endoscopic endonasal approach provides an optimal corridor for the resection of select anterior midline skull base tumors.
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Reconstruction using vascularized regional flaps, such as the nasal-septal flap, has significantly decrease morbidity, including rates of cerebrospinal fluid leak.
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We recommend a 2-surgeon, 4-hand approach with collaborative expertise in rhinology and neurosurgery.
According to the Central Brain Tumor Registry of the United States, meningiomas are the most common primary brain tumor. Anterior skull base meningiomas represent 6% of all meningiomas. This article provides an overview of meningiomas and focuses on the management of anterior skull base meningiomas in which endoscopic endonasal surgery is a treatment option.
Epidemiology
Meningiomas comprise 24% to 30% of all primary intracranial tumors and have an annual incidence of 13 per 100,000. The incidence increases in the fourth and fifth decades with a peak in the sixth decade. Female to male ratio is 1.7:1 with an even greater female predisposition in the reproductive age group (3.5:1).
Meningiomas are found incidentally in 1.4% of autopsy cases. Multiple meningiomas represent less than 10% of all sporadic meningiomas; however, they represent a greater cluster in patients with neurofibromatosis type 2 (NF2).
Epidemiology
Meningiomas comprise 24% to 30% of all primary intracranial tumors and have an annual incidence of 13 per 100,000. The incidence increases in the fourth and fifth decades with a peak in the sixth decade. Female to male ratio is 1.7:1 with an even greater female predisposition in the reproductive age group (3.5:1).
Meningiomas are found incidentally in 1.4% of autopsy cases. Multiple meningiomas represent less than 10% of all sporadic meningiomas; however, they represent a greater cluster in patients with neurofibromatosis type 2 (NF2).
Cause and pathophysiology
Meningiomas are thought to grow from the arachnoid cap cells; however, intraosseous and intraventricular meningiomas have been reported. There are several theories regarding the cause and development of meningiomas.
Meningiomas and the Female Sex
Meningiomas are most common in women; the female to male ratio tends to be greater in the younger age group. The ratio in postmenopausal women is 1.7:1 compared with 3.5:1 in the reproductive age group. This difference has been explained by the presence of progesterone and estrogen receptors in 88% and 39% of the lesions respectively. In addition, women on estrogen-only hormonal therapy have a slightly increased risk of developing a meningioma, although the same link has not been found for women on estrogen-progestin hormonal therapy.
Meningiomas and History of Radiation
Meningioma development is strongly related to a history of ionizing radiation exposure. This relationship has been witnessed in the survivors of the Hiroshima atomic bombing and later after the delivery of radiation therapy to pediatric patients diagnosed with cancer. The dose of radiation is inversely related to the time to meningioma development. The average interval for meningioma development is 19 to 24 years after exposure to high-dose radiation, compared with 35 years after lower doses of radiation. Radiation-induced meningiomas tend more to be atypical, multifocal meningiomas, with higher proliferative indices, and they occur at younger ages.
Genetic Predisposition of Meningiomas
Neurofibromatosis type 2
The pathways that are responsible for the transformation of arachnoid cap cells to meningiomas have been evaluated. One of the common pathways that is affected involves the NF2 gene. Loss of heterozygosity of chromosome 22q results in its inactivation. This gene is thought to encode Merlin, a tumor suppressor gene.
Non–neurofibromatosis type 2
In families with positive family history and without features of NF2, pathways other than the NF2 gene have been implicated, including vascular endothelial growth factor, Hedgehog gene, and mTORC1 (mammalian target of rapamycin complex 1), which is responsible for tumor suppression.
Head Injuries and Meningiomas
Several theories have been proposed regarding the development of meningiomas after head injuries. One hypothesis is that local alteration of the blood-brain barrier as a result of head injury is associated with extravasation of inflammatory mediators. These mediators include cytokines, histamines, and bradykinins, and may predispose patients to meningioma development. In addition, genes that control transcription regulation and signal transduction have been shown to be altered following head injuries. Although reports comprising smaller case numbers continue to arise that suggest a link between head injury and meningioma development, a large prospective observational study of 2953 patients with head injuries failed to show a clear link. In addition, women have both a higher incidence of meningiomas and a lower incidence of head trauma compared with men, which goes against this theory.
Classification
According to Grade
Meningiomas are divided into 3 grades according to their histologic features as defined by the World Health Organization (WHO). Grade I meningiomas represent 94.6% of all meningiomas. They are considered benign, tend to grow more slowly, and have a lower risk of recurrence. WHO grade II meningiomas (atypical) are more aggressive and represent 4.2% of all meningiomas, whereas WHO grade III meningiomas (anaplastic) are malignant and represent 1.3%.
According to Site
In addition to the WHO grading system, meningiomas are classified according to the primary dural attachment site of the tumor. Initially proposed by Harvey Cushing and Louise Eisenhardt, this classification helps describe the natural history, including the development of clinical signs and symptoms, and helps in planning the appropriate surgical approach.
Meningiomas have been classified broadly based on supratentorial and infratentorial location, but are commonly subdivided by specific location. Most commonly, meningiomas arise in the convexity (34.7%) and parasagittal locations (22.3%). Infratentorial meningiomas represent 10% of all meningiomas, of which almost 50% are in the cerebellar convexity. The anterior skull base represents the site of origin for 8.8% of all meningiomas. The most common midline anterior skull base dural attachment is the tuberculum sellae (3.6%), followed by the olfactory groove (3.1%).
Pathology
Gross Pathology
Most meningiomas are firm in consistency, are well demarcated in relation to surrounding tissues, and have a broad dural attachment. It is common for these types of tumor to invade the underlying dura and dural sinuses, and they occasionally involve the bone of the calvarium, causing hyperostosis. In addition, meningiomas may invade beyond the bone and even infiltrate the skin and extend to the extracranial compartments such as the orbit. In the midline of the anterior skull base, meningiomas are primarily perfused by the ethmoidal arteries ; however, other meningeal and ophthalmic branches can also perfuse them. Although less common, large tumors can obtain perfusion from branches of the frontopolar arteries or other smaller branches from the anterior cerebral arteries. They also may attach or encase the cerebral vessels. Malignant meningiomas can also invade the walls of these vessels.
Clinical presentation of midline anterior skull base meningiomas
Olfactory groove meningiomas originate from the meninges that overlie the cribriform plate of the ethmoidal bone and the region bounded by the frontosphenoid, sphenoethmoid, and frontoethmoidal sutures ( Fig. 1 ). When these tumors grow large, they can extend posteriorly to the planum sphenoidale. They tend to present at larger sizes than meningiomas arising in different skull base locations. Symptoms tend to develop later in their course because the surrounding structures (ie, the frontal lobes and the olfactory nerves) tolerate compression longer than other neural structures. Symptoms appear gradually and are rarely recognized in the initial stages. In 30% to 40% of patients, early symptoms can include behavioral changes, personality changes, and headaches. Anosmia, despite occurring in 13.3% to 64.5% of patients and being retrospectively noted early in the course, is rarely the symptom leading to tumor discovery. Visual symptoms usually appear as late manifestations because they require a very large tumor to be present. Seizures are the presenting sign in 13.3% to 17.8%, whereas in 3.8% to 13.3% of cases the tumors are found incidentally. Foster-Kennedy syndrome refers to unilateral optic atrophy, unilateral anosmia, unilateral central scotoma, and contralateral papilledema. Despite the classic association of Foster-Kennedy syndrome with olfactory groove meningiomas, it is rare given that modern high-quality imaging typically leads to the diagnosis before the meningioma reaches a size large enough to cause this group of symptoms.
The planum sphenoidale, which is the portion of the anterior skull base corresponding with the bony roof of the sphenoid sinus, is another common site of origin for anterior skull base meningiomas. Planum sphenoidale meningiomas tend to push the optic nerves and chiasm as they grow posteriorly and inferiorly, as well as displacing the frontal lobes laterally. The tumors are initially silent because they rarely involve the pituitary stalk or the visual pathway. Usually patients present with headaches (63%) followed by visual impairment (14%); less commonly they present with endocrinopathies caused by impairment of the pituitary stalk.
The tuberculum sellae, which is the junction of the sella turcica with the anterior skull base, gives rise to meningiomas with a distinct presentation compared with the other anterior skull base meningiomas. Their origin lies in the dural attachment at the chiasmatic sulcus, which is just medial to the bilateral optic foramina anterior to the sella. Tuberculum sellae meningiomas can displace the optic nerves and chiasm. The direction of displacement depends on whether the optic chiasm lies anterior to the chiasmatic sulcus (prefixed chiasm, superior displacement) or posterior to the chiasmatic sulcus (postfixed chiasm, posterior and lateral displacement). In addition, tuberculum sellae meningiomas have a propensity to invade the optic canals, resulting in early visual symptoms. Visual deficits are the most common presenting symptoms (84%–89%), followed by endocrinopathies (8.4%–25.9%), headaches (17.1%–23.2%), and seizures (<2.5%). Tuberculum sellae meningiomas are found incidentally in 4.1% to 14.3% of cases.
Radiology
Meningiomas usually appear isodense on computed tomography unless they have regions of calcifications, in which case those regions are hyperdense. They are isointense on T1-weighted MRI and they uniformly enhance with gadolinium contrast. A dural tail, enhancement of the dural perimeter surrounding the dural attachment, is present in 58% to 72% of cases.
Given that most meningiomas are benign and grow slowly, the amount peritumoral edema is typically minimal to none on T2 and fluid attenuation inversion recovery MRI sequences. However, edema is frequently observed in atypical and malignant meningiomas. Cyst formation, if present, occurs at the peripheral part of the tumor.
Although meningiomas are the most commonly seen extra-axial tumors, other possibilities must not be discounted in the differential diagnosis, including dural-based metastases, idiopathic hypertrophic pachymeningitis, and granulomas.
Management
Typical benign meningiomas have a slow growth rate and a mean doubling time of 5.2 years. The growth rate tends to be higher in younger patients and lower in the presence of calcification. Therefore initial observation with close imaging follow-up can be considered, especially in elderly patients, those with multiple comorbidities, asymptomatic patients without proven growth, and in those with a calcified meningioma. In patients who are symptomatic and/or having demonstrated growth, treatment with surgery or radiation can be considered.
Surgical treatment
The surgical approach selected to treat meningiomas differs based on site of dural attachment. A key selection criterion when selecting the surgical approach is the ability to obtain maximum extent of resection, which includes resection of the tumor in addition to the pathologic dural attachment and hyperostotic bone, because this is predictive of rate of recurrence. In 1957, Simpson was the first surgeon to describe the different grades of meningioma resection, with observation of the rate of recurrence of each grade ( Table 1 ).
