Final Diagnosis -- Seven Year Old Girl with Meningioangiomatosis

DISCUSSION:

Meningioangiomatosis (MA) is a rare hamartomatous lesion of the cerebral cortex and sometimes the overlying leptomeninges that was first described by Bassoe and Nusum in 1915 in association with neurofibromatosis (NF) (2), and the name MA was coined by Worster-Drought et. al., in 1937 (21). In 1986, Halper et. al. reported 6 cases of MA and elegantly reviewed 17 other cases from the literature (8). Five of their cases were not associated with NF. Harada et. al., reviewed 13 similar cases (9). Approximately 50 cases are now described in the English language literature. Cases associated with NF comprise less than one-third of the reported cases (where commented upon) and all were discovered at autopsy (8, 18). These patients have a mean age of 32 years (range: 15-70), and male: female of 2: 1. About one-third of these cases had multiple lesions (8, 18). The exact incidence of MA in NF is unknown; it was seen in 4 of 11 patients with "central" NF at autopsy (18), and in 1 of 135 patients with von Recklinghausen's disease in a clinical study (10). It appears to be far more common in NF-2 than in NF-1 (14). Most cases of MA, however, are not associated with NF. There are clinical differences between the sporadic cases and those cases of MA associated with NF. In the sporadic cases the ratio of male to female patients is more equal and the mean patient age is younger (17 years, range: 11 months-55 years). Also, these patients usually present with intractable seizures (1, 3, 6-9, 15, 16, 19). Duration of seizures range from 2 months to 30 years before diagnosis, and are occasionally preceded by febrile convulsions in infancy (8) . Headache is an uncommon presenting symptom (11, 17). Rarely MA is found at surgery for other lesions (13, 20).

Topographically, MA affects the cerebral cortex in 90% of the cases and is usually in the frontal or temporal lobes. Other locations include the third ventricle, thalamus and cerebral peduncles (8) , and the brain stem (12). Interestingly, about 80% of the cases are on the right side. Detailed neuroradiologic features of MA have been provided by many authors (1, 7, 19). Computerized tomography reveals variable amount of calcifications with little or no contrast enhancement. By magnetic resonance imaging, the abnormality is confined to the cortex and consists of isointensity or hypointensity on T1-weighted images. The T2-weighted images reveal a heterogeneous cortical mass surrounded by an area of increased signal intensity.

The gross appearance of MA is usually a sharply demarcated lesion with or without calcification of overlying leptomeninges. In this case, the borders were not apparent and microscopically, the lesion was present in all sections. The degree of leptomeningeal calcification is also variable (11). Abnormally prominent blood vessels may be seen and an associated arteriovenous malformation was seen in one instance (18). The histologic appearance varies with chronicity of the lesion (4). The current case illustrates the typical histologic appearance of MA (see above). In addition to psammoma bodies, some cases, possibly more chronic ones, demonstrate pronounced leptomeningeal calcifications or even ossification (4, 11). The presence of neurofibrillary tangles in the majority of cases is of particular interest, and may represent degenerative change in entrapped neurons (8). These tangles are typically tau and Alz-50 reactive, but less reactive for ubiquitin (6). Granulovacuolar degeneration can also be seen (4).

The pathogenesis of MA is unclear. It is currently classified as a hamartomatous lesion, but its association with NF-2 is intriguing. The NF-2 gene has been located on chromosome 22 and meningiomas are a common tumor in NF-2. Meningiomas (including those not associated with NF-2) often have monosomy 22 or other karytypic abnormalities associated with chromosome 22. It is thought that there is a meningioma-related tumor suppressor gene on chromosome 22, however, it appears that this putative gene is distinct from the NF-2 gene (5). While MA is obviously an abnormal proliferation involving vessels and meningothelial cells, it is uncertain if it is a static lesion or a very gradual process. It has a very low proliferation index (16, 19) .

Total surgical resection is the treatment of choice for MA and the prognosis following surgery is excellent with cure of seizures in almost all cases (8, 9, 16).

References:

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