Current Management of Meningiomas
Current Management of Meningiomas
ABSTRACT: Although generally benign tumors, meningiomas can cause serious neurological injury and, at times, vexatious management difficulties. Currently, the accepted management of these tumors is attempted total surgical excision when technically possible and associated with an acceptable risk. However, even with innovations in instrumentation and refinements in surgical technique, the goal of total resection may not be achievable. For these patients, and for those with recurrent tumors, options for treatment include reoperation, radiation therapy, and chemotherapy. Recent developments in surgical technique and instrumentation, radiosurgery, and brachytherapy have increased the treatment options, while clinical trials with tamoxifen and mifepristone (RU486) are adding information on the effectiveness of these drugs as chemotherapeutic agents. While the search continues for a uniformly successful management plan, physicians must be aware of the available options and try to help the patient decide which treatment is appropriate, based on current medical knowledge. [ONCOLOGY 9(1):83-100]
Histologically, meningioma is a typically benign neoplasm that would not present a therapeutic challenge if located in any less vital or less anatomically complex region of the body than the intracranial or intraspinal spaces. When located inside the cranium, and especially along the skull base, this usually benign tumor must be viewed as a locally aggressive soft-tissue tumor that will recur if incompletely treated. The following case presentation highlights just such a problem.
In 1965, a 31-year-old woman had a left frontotemporal craniotomy and a subtotal resection of a sphenoid ridge meningioma. Postoperatively, a wound infection led to the removal of the craniotomy bone flap. In 1968, progressive left-sided proptosis due to tumor regrowth developed, and the patient underwent a left orbital exenteration with subtotal removal of the meningioma. Progressive enlargement of the residual meningioma led to two subsequent cranial operations in 1974. Following these surgeries, external beam radiation to a dose of 50 Gy was delivered. The patient remained stable for 17 years.
In 1991, an increased frequency of seizures, somnolence, and memory loss led to reinvestigation. Massive tumor recurrence was found. The initially left-sided sphenoid ridge meningioma had now spread to the right middle fossa and into the posterior fossa. The large right middle fossa component of the tumor was resected. In early 1994, the patient, now 59 years old, developed an ataxic gait and right-sided hearing loss. Enlargement of the tumor was noted. The patient was enrolled in an experimental trial using the antiprogesterone agent mifepristone (RU486). Progressive tumor enlargement with the onset of obstructive hydrocephalus led to the discontinuation of the medication and the insertion of a ventriculoperitoneal shunt. The patient's current magnetic resonance (MR) images are shown in Figure 1. Surgical removal of the large petroclival component of the meningioma has been recommended.
Reported incidence rates of meningioma vary from less than 1 to more than 6 per 100,000 population [1,2]. If the results of three large recent studies of intracranial neoplasms are combined, the overall incidence of meningioma is 2.6 per 100,000 population [1,3,4]. The ratio of male to female cases ranges from 1:1.4 to 1:2.8. The incidence of intracranial meningioma increases with age [1,3,4]. The rates peak in the sixth decade for males and in the seventh for females. These peak rates are 6.0 and 9.5 per 100,000, respectively . Autopsy data suggest that the declining incidence rates beyond the seventh decade may be the result of a less aggressive investigative posture in the elderly .
The World Health Organization (WHO) classification of meningiomas is shown in Table 1. Numerous histologic variants of meningioma exist, none of which has any prognostic significance; all are considered histopathologically benign tumors. The most common of these variants are the meningothelial and fibrous meningiomas (Figure 2).
Certain histopathologic features, which can be detected by light microscopy, portend an increased tumor aggressiveness and increased likelihood for recurrence (Table 2) [6,7]. It is these features that define the atypical meningioma. The diagnosis of malignant meningioma generally requires histologic evidence of brain invasion or distant metastasis, which, in most cases, is accompanied by further evidence of aggressivity such as is seen with the atypical meningiomas. An exception to this requirement is the finding of a papillary pattern . This pattern is associated with a predictable aggressive behavior, with late distant metastases occurring with significant frequency . When dissemination occurs, the more common sites of implantation and growth are the lungs and/or pleura, bones, abdominal viscera (especially the liver), and lymph nodes .
Because the identification of histologic features of aggressiveness is occasionally imprecise, and their presence does not necessarily correlate with future regrowth or recurrence of the tumor, researchers have attempted quantitative measurements of various parameters. Using flow cytometry, May et al  have shown that recurring meningiomas have a significantly higher proliferative index (% S-phase + % G(2)/M-phase) than do nonrecurrent meningiomas. They indicated that a proliferative index of more than 20%, irrespective of the histopathologic appearance, strongly suggested that the tumor would recur.
The determination of the bromodeoxyuridine (BUdR) labeling index or of the number of argyrophilic nucleolar organizer regions (AgNOR) has been used to identify intracranial meningiomas with a higher propensity to recur. Hoshino et al  found that a BUdR labeling index of 1% or higher was indicative of meningiomas with a faster than typical growth rate (higher proliferative potential) and that meningiomas with a BUdR labeling index of 5% or higher had a 100% recurrence rate. The recurrence rate dropped to 55.6% for meningiomas with a BUdR labeling index between 3% and 5% and to 30.6% for those with a BUdR labeling index between 1% and 3% [12,13]. Chin and Hinton  reported that the mean AgNOR counts were statistically different among benign (245 ± 156), atypical (497 ± 135), and malignant meningiomas (921 ± 59). They also noted a statistically different AgNOR count for recurrent meningiomas (544 ± 76) when compared with nonrecurrent meningiomas (329 ± 183).
Finally, positron emission tomography (PET) studies have shown glucose utilization to be lower (1.9 mg/dL/min ± 1.0) in nonrecurring tumors than in recurrent tumors (4.5 mg/dL/min ± 1.9) .
Contrast-enhanced MR imaging provides the best means of detecting meningiomas . Most meningiomas enhance intensely and homogeneously with intravenous paramagnetic contrast material, and in approximately 10% of cases, small additional meningiomas are encountered that are missed on unenhanced MR images. Likewise, contrast enhancement of the dura extending away from the margins of the mass is typical of meningioma, although it can be seen with other dural-based lesions. This "dural tail" can indicate tumor extension, and its resection is important to reduce the risk of recurrence. Postoperative enhanced MR imaging has also been found to be more sensitive and specific in the detection of residual or recurrent meningioma. Thick and nodular enhancement has a high correlation with recurrent or residual neoplasm .
The MR characteristics of meningiomas are relatively consistent. On noncontrasted T(1)-weighted images, 60% to 90% of meningiomas are isointense, whereas 10% to 30% are mildly hypointense when compared with gray matter. T(2)-weighted imaging reveals that 30% to 45% of meningiomas have increased signal intensity, whereas approximately 50% are isointense to gray matter [16,18-20].
Vascular distortion or encasement and tumor vascularity are better assessed by MR imaging than by computed tomography (CT) scanning. Flow-voids produced by flowing blood identify the vasculature local to the tumor (Figure 1).
There is increasing interest in using MR characteristics to tissue-subtype meningiomas preoperatively. The results of these studies have been varied, with some reporting 75% to 96% accuracy, and others finding no correlation [18-21]. The MR characteristics that allowed accurate preoperative identification of meningioma subtypes were confined to findings on T2-weighted studies. Specifically, meningothelial meningiomas were found to have a consistently higher signal intensity on T2-weighted sequences than did fibroblastic or transitional meningiomas, which demonstrated a higher relative signal intensity on intermediate images. High signal intensity on T2-weighted images has also been correlated with microscopic hypervascularity and soft tumor consistency .