Meningioma of the skull base, presenting with multiple cranial nerve palsies
In this case, the patient presents with multiple cranial nerve abnormalities on the left side, which have developed gradually with no systemic symptoms. Intramedullary (intra-axial) or extramedullary (extra-axial) lesions may cause multiple cranial neuropathies. An intramedullary process such as a posterior circulation infarct is likely to produce crossed findings with ipsilateral cranial nerve deficits and long tract signs on the opposite side of the body. There is no evidence of crossed findings in this case. In contrast, extramedullary syndromes typically involve adjacent cranial nerves, often in succession. Long tract findings are less common and, when they occur, usually occur later and are mild. The differential diagnosis in these cases includes trauma, localized infections such as herpes zoster, granulomatous diseases (such as Wegener's granulomatosis, sarcoidosis, or tuberculous meningitis), meningeal inflammation, and compression by tumors or aneurysms. The history and neurologic findings in this case are more consistent with an evolving extramedullary process. MR imaging in this patient defines a strongly enhancing mass lesion located at the skull base, encasing much of the brainstem, and extending inferiorly to the cervical region, where it displaces the two major branches of the left common carotid artery. This mass overlaps into the middle cranial fossa, with prominent tentorial thickening and enhancement, and also encroaches on the sphenoid sinus and enters into the left internal auditory canal.
The differential diagnosis of enhancing mass lesions located at the skull base is extensive, and the discussion will be confined to the more frequently encountered tumors that may mimic this patient's presentation.
Paragangliomas, including carotid body tumors, glomus vagale, glomus jugulare, and glomus tympanicum tumors, are slow-growing, highly vascular tumors that may present with skull base involvement (8). Pulsatile tinnitus is often a clue to the emergence of a glomus tympanicum paraganglioma. Early development of a jugular foramen syndrome (involvement of cranial nerves IX, X and XI) may also herald the emergence of a paraganglioma. On MR imaging, a characteristic "salt-and-pepper" appearance is usual, owing to hyperintense tumor (salt) and flow voids of tumor vessels (pepper). These features were not observed in this patient's MRI studies. On dye angiography, these tumors are extremely vascular, with rapid shunting of dye through the tumor vessels into an early venous phase (again not noted in this patient's studies). Other extremely vascular masses that can involve the skull base include arteriovenous malformations, hemangiomas, and glomus tumors arising as hyperplasia or hamartomatous development of glomus bodies.
Carcinomas arising in the nasopharynx or sinuses may invade the skull base, typically producing substantial local destruction and pain as neurovascular structures become involved. The substantial displacement of carotid branches (rather than invasion or infiltration), and virtual absence of edema in adjacent brain tissue, as noted on this patient's imaging, would be atypical for an aggressive malignancy.
Vestibular schwannomas, often known as "acoustic neuromas," typically arise from the vestibular portion of the eighth cranial nerve, and present with early hearing loss, tinnitus, and vertigo prior to invasion of the cerebello-pontine angle and involvement of other cranial nerves, such as V, VII and the IX-XI complex; involvement of cranial nerve VI is unusual. Schwannomas may be isointense to normal brain on unenhanced T1-weighted MR images, as in this patient, and may substantially enhance with gadolinium. Vestibular schwannomas in the cerebello-pontine angle typically manifest as round or ovoid masses, in contrast to the semilunar shape of meningiomas in this region. Many tumors of the cerebello-pontine angle can involve the internal auditory meatus, however, an enlarged internal auditory meatus is considered highly suggestive of vestibular schwannoma. On dye angiography, schwannomas are usually described as hypovascular, although occasionally schwannomas may exhibit substantial vascularity. Feeding vessels typically derive from the external carotid branches, with occasional contributions from branches of the vertebrobasilar system (7). Vascular supply from branches of the internal carotid artery would be extremely rare for vestibular schwannomas.
Meningiomas of the skull base can present in a variety of fashions. They may be isointense to normal brain on unenhanced T1-weighted sequences, and typically enhance strongly with gadolinium. These slowly growing tumors classically displace rather than invade nearby tissue, although they may infiltrate the dura, producing thickening and increased ehnacement, as was seen in the tentorium in this patient. Arteriography of skull-base meningiomas shows multiple feeding arteries, often with a dual vascular supply arising from branches of the external carotid artery and the internal carotid artery. The late arterial and capillary phases of angiography are typically prolonged in meningiomas, without the early venous filling more typical of paragangliomas and glomus tumors.
Angiographic evaluation of this patient's tumor showed vascular supply from the ascending pharyngeal artery (the 2nd branch of the external carotid artery) and also transosseous supply from the occipital artery, the 5th branch of the external carotid artery. In addition, there was vascular supply to the tumor from the meningohypophyseal artery, a branch of the cavernous portion of the internal carotid artery. Not posted on the angiographic summary, but discussed by the neuroradiologist, there was a prolonged tumor blush, without early venous filling, on this patient's study.
The MR imaging and angiographic findings, together with the the patient's age, gender, and clinical progression, were felt to be highly suggestive of a meningioma loacted at the skull base, with extension throughout the posterior fossa and through the foramen magnum into the high cervical region. An atypical presentation of a vestibular schwannoma was considered much less likely, for the reasons outlined above. It is particularly important to be familiar with the epidemiology, pathologic variants, and imaging findings of meningioma, as diagnosis of these tumors is often made on the basis of typical clinical and radiographic findings, and treatment is often initiated without histological confirmation.
Meningiomas occur in adults primarily between the ages of 40 and 60. The incidence in women outnumbers that in men by a ratio of 2-4 to 1. Only 1-2% of meningiomas occur in children under 16 years of age, often in atypical locations. Meningiomas are the most common nonglial primary CNS tumor in adults and represent 15-20% of all primary brain tumors. The incidence of symptomatic meningiomas is 2-3 per 100,000 people (1, 6).
Meningiomas are usually extra-axial, dural-based lesions. They most commonly arise from meningiothelial (or meningo-epithelial) cells in the arachnoid granulations, although some may arise from arachnoid membrane associated with cranial nerves or the choroid plexus. These neoplasms are generally sharply circumscribed, even in tumors with extensive growth. They classically displace nearby tissue rather than invading it, although they may infiltrate the dura and sometimes the underlying brain. On gross examination, meningiomas often appear lobulated, and they may even have a cleft of arachnoid membrane with prominent vessels and trapped CSF. Their consistency varies from soft to tough, or even gritty as some tumors have extensive calcifications. They frequently have small areas of necrosis or small focal hemorrhages, but rarely demonstrate gross hemorrhage.
Histologically, meningiomas are heterogeneous neoplasms. Psammomatous calcifications and meningothelial cells aggregated into whorls are present in many of these lesions (meningotheliomatous meningiomas). Other tumors are characterized by abundant reticular and collagenous fibers (fibrous meningiomas) while some are highly cellular and vascular (angioblastic meningiomas). In the WHO classification of these tumors, 88-94% of meningiomas are benign or typical, 5-7% show cellular atypia, and only 1-2% are anaplastic or malignant (1, 6).
Chromosome 22 monosomy in tumor cells has been reported in a high percentage of cases, and long arm deletions are also common. Neurofibromatosis type 2 (NF-2), caused by a mutation of the NF-2 gene on chromosome 22, also predisposes to the formation of meningiomas. Progesterone and estrogen receptor expression has been demonstrated in meningiomas, possibly correlating with the gender predisposition of these tumors (6).
Many meningiomas are incidentally found on imaging studies or at autopsy, making it difficult to estimate a true incidence. It is believed that fewer than 10% of all meningiomas are ever symptomatic. The clinical presentation, as would be expected, varies widely depending on the location of the lesion. Most of these tumors are supratentorial (90% of cases). In general, they occur at sites of arachnoid granulations, along dural sinuses, or at sutures. The most common sites for these tumors to arise are in the parasagittal regions and cerebral convexities (25% and 20% respectively). These cases may present with hemiparesis or seizures. Other common locations include the sphenoid ridge (15-20%), olfactory groove (5-10%), and parasellar regions (5-10%). Sphenoid lesions often cause early visual field defects. Meningiomas arising in the cavernous sinus may present with multiple cranial nerve abnormalities (6).
Ten percent of meningiomas occur in the posterior fossa. Approximately 2% of intracranial meningiomas have no clear dural attachments, and arise in the ventricles, optic nerve sheath or pineal regions. Only 1% of meningiomas arise outside the CNS dura. In these cases, the tumor mass may extend into the sinuses and nasal cavity, or along the vertebrae. Infrequently, meningiomas may also occur in the parotid glands or even the skin.
Location and resectability are the factors that most affect the clinical outcome. For example, a tumor occurring on the convexity of the brain (that can usually be completely resected) will be expected to have a much more benign course than a tumor occurring in the cavernous sinus or skull base, even if the histology is identical. Given similar location and resectability, histological factors clearly affect the clinical course. Recurrence rates are low (3-7% over five years) in typical meningiomas, higher in tumors with cellular atypia (up to 33%), and highest in anaplastic meningiomas (almost 75%). Meningioma metastases are rare, occurring in only 0.1-0.2% of cases. It is important to note that tumor histology does not correlate absolutely with metastatic potential, as both histologically benign and anaplastic meningiomas have been reported to metastasize (1, 6).
CT scanning with contrast detects over 90% of intracranial meningiomas. The tumor usually appears as a well-circumscribed, round or smoothly lobulated mass next to a dural surface. These tumors appear as heterogeneous, hyperdense masses on non-contrasted CT scans in 70-75% of cases, with calcification seen in 20-25%. Cystic areas may be seen in 10-15% of cases and usually correspond to cysts of trapped arachnoid and pools of CSF, as is seen on gross pathological examination. Edema in the region around the tumor is seen in 60% of cases and may be quite extensive, mimicking that evoked by tumor metastases. On contrasted studies, these tumors intensely, and relatively uniformly, enhance in 90% of cases.
On MR imaging, meningiomas typically appear isointense with gray matter on T1-weighted sequences. Over 95% strongly enhance with gadolinium contrast. The CSF clefts commonly noted in pathologic specimens are often evident between the tumor and adjacent brain on MR imaging. Sixty percent of meningiomas have a "dural tail," a collar of thickened, enhancing tissue at their dural attachments. While this radiographic feature is not specific for meningiomas, it is highly suggestive of the diagnosis.
Meningiomas may be evaluated by angiography as the majority of the tumors are vascular. Large tumors often have a dual vascular supply, with meningeal vessels supplying the central portion and the tumor periphery supplied by pial branches from the anterior, middle or posterior cerebral arteries. Selective injection of the external and internal carotids may show this dual vascular supply. The typical parasagittal or convexity tumor may display a "sunburst" pattern of enlarged dural feeding vessels within the tumor. There is usually a prominent, prolonged vascular blush on the late arterial and capillary-phase films. This prolonged vascular blush has been dubbed the "mother-in-law sign," according to Dr. James Smirniotopoulos, who noted that "it comes early and stays late!" (6)
Treatment of skull based meningiomas has changed over the last several years, reflecting technological advances in the areas of microsurgery as well as radiotherapy. Observation is still recommended in many asymptomatic or mildly symptomatic patients. Microsurgical approaches have improved the approach to skull base lesions, but total resection rates for meningiomas in this region remain low due to their precarious location and vascularity (4). The likelihood of accomplishing total resection correlates well with six pre-operative factors: 1) prior irradiation, 2) vessel encasement, 3) multiple fossa involvement, and palsies of the 4) oculomotor, 5) trigeminal, or 6) abducens nerves. Levine et al. have proposed a grading system based on these criteria in which increasing numbers of these factors correlate with decreased total resection rates and inferior post-operative performance status (3, 5). Adjuvant focused radiotherapy has been shown to treat residual tumor as well as tumor recurrences with improved progression-free survival rates. Patients who are not surgical candidates may be treated with radiotherapy alone, with the goals of palliation and a higher probability of recurrence-free survival (2, 3, 4). Thus far, adjunctive chemotherapy appears to be of limited value, even in malignant lesions (4).
This patient was diagnosed clinically and radiographically as having a meningioma of the skull base, extending into the upper cervical spine region and involving the carotid arteries on the left. She had palsies of the V, VI, VIII, IX, X, XI and XII cranial nerves on the left, consistent with the imaging findings. In addition, there was weakness in the proximal left upper extremity, possibly related to mass effect or edema, as there did not appear to be direct extension of the mass into the region of the brachial plexus or lower cervical areas.
The patient was not considered a good candidate for surgical resection, owing to the extent of tumor, vessel encroachment, and substantial cranial nerve involvement. She underwent stereotactic external beam irradiation with minimal effect on her symptoms, and has been monitored with periodic neuroimaging over a course of more than eight years. More recently she has begun to experience tingling and pain in the left arm and shoulder, and is being re-evaluated by the Neurosurgery Service for partial resection of the tumor mass.
We thank Terrence Riley, M.D., of the Ben Taub General Hospital Neurology Service, for assistance with the development of this case.
-- Dennis R. Mosier, M.D., Ph.D.