An 11-year-old boy presented with a 2-year history of complex partial seizures refractory to multiple therapeutic regimens. Past medical history was significant for a behavior disorder, depression, and a learning disability. There was no history of central nervous system infection, head trauma, or febrile seizures. The family history was noncontributory. Results of physical examination were normal, with no evidence of cutaneous lesions. Electroencephalographic studies showed left frontal and right anterior temporal seizure foci with focal slowing. Magnetic resonance imaging with and without contrast demonstrated a heterogeneous lesion of the right anterior and lateral temporal lobe with subtle enhancement of the leptomeninges and subjacent temporal lobe parenchyma. (Figure 1). A complete workup for demyelinating and neurodegenerative diseases was performed and was negative.

A frontal-temporal craniotomy was performed with a large right temporal lobectomy, including removal of the amygdala and hippocampus. Histopathology revealed a proliferation of blood vessels and meningothelial cells concentrically arranged around vessels in the meninges, underlying cortex, and white matter (Figure 2). Scattered meningothelial cells demonstrated intranuclear cytoplasmic invaginations. Focal epithelial membrane antigen positivity was observed in the meningothelial cells. Intervening cortex and white matter showed reactive gliosis and focal perivascular sclerosis. Psammoma bodies were occasionally observed (Figure 3) in association with the lesion in the cortex. Mitotic figures, necrosis, prominent nucleoli, and marked pleomorphism were not identified.

What is your diagnosis?

Meningioangiomatosis is a cerebral lesion that was first described by Bassoe and Nuzum1 (1915) as an incidental autopsy finding in a patient with von Recklinghausen disease. The disease was later named by Worster-Drought et al.2 Von Recklinghausen disease (neurofibromatosis type 1 [NF1]) is inherited as an autosomal-dominant condition in which the gene defect has been located to chromosome 17.1–10 Neurofibromatosis type 1 has long been associated with vascular abnormalities and various types of heterotopia or dysplasia within the central nervous system, including heterotopic gray matter, excessive myelination within gray matter, discrete foci of cortical dysplasia, subependymal glial nodules, ependymal ectopia, and intramedullary schwannosis.3 Although historically associated with NF1, growing evidence indicates a greater association of meningioangiomatosis and neurofibromatosis type 2 (NF2).4 The NF2 gene on chromosome 22 appears to function as a tumor suppressor.4 Neurofibromatosis type 2 patients have inactivating germline mutations of the NF2 gene, predisposing these patients to schwannomas and meningiomas.4 Although it is commonly associated with NF1 or NF2, a significant number of meningioangiomatosis cases have been reported in which the clinical stigmata and family history of NF1 and NF2 are absent.3–10 

The radiographic findings of meningioangiomatosis may show a variety of features. Computed tomography findings show variable amounts of calcification with little or no contrast enhancement. Magnetic resonance imaging findings vary with regions of hypointensity and hyperintensity, depending on the amount of calcification and edema present. Contrast enhancement is common but is not the rule. In view of the wide spectrum of findings, radiographic imaging does not permit a precise diagnosis.8 

Electrophysiological studies have revealed a range of abnormalities.5 The epileptic foci can resemble a focal, nondysplastic lesion, whose epileptogenicity is produced by adjacent cortex or is similar to that of cortical dysplasias, in which the lesion itself produces spikes.5 

Meningioangiomatosis shares the microscopic features of both meningioma and angioma.3,4 Neuropathologic findings usually consist of thickened and opaque leptomeninges containing abnormal vessels without any evidence of a neoplastic process.3 Occasionally, prominent meningothelial cell proliferation in the leptomeninges may be evident, reminiscent of a meningioma. The lesion is characterized by perivascular meningothelial cell proliferation with collagen deposition, involving the cortex and sometimes the underlying white matter.7,8 Leptomeningeal and parenchymal mineralization may occur, ranging from psammoma bodies to dense osteoid formation.3,4,7 Neurofibrillary tangles, similar to those observed in the patient with Alzheimer disease, have been noted and are most likely the result of nonspecific degenerative changes.4 Prominent mitotic activity, necrosis, small cell change, prominent nucleolation, or marked nuclear pleomorphism of cells are not observed.4 

Because of the complexity of histologic features, a specific diagnosis of meningioangiomatosis is difficult to make. Tumors such as a meningioma, schwannoma, or leptomeningeal sarcoma may have similar histologic findings. Immunocytochemistry may aid in the differentiation of schwannoma versus meningoma. Schwannomas are diffusely S100 protein positive and epithelial membrane antigen negative, whereas only 20% of meningiomas stain focally S100 protein positive and 80% stain epithelial membrane antigen positive.4 Leptomeningeal sarcoma can be excluded, as they follow an aggressive clinical course and are characterized by more aggressive histologic features, such as necrosis, prominent mitotic activity, nuclear pleomorphism, and loss of architectural pattern. In Sturge-Weber syndrome, capillarovenous leptomeningeal angiomatosis or multiple intracranial hemangiomatosis can appear, as is the case with meningioangiomatosis, but this syndrome lacks the meningothelial cell component.3,8 

Although the pathogenesis of meningioangiomatosis is still unclear, 2 main theories have been proposed. The first theory holds that the lesion arises from an initial angiomatous component, with the secondary proliferation of meningiomatous elements.3–6,8 The leptomeninges and associated arachnoidal cap cells are known to surround blood vessels as they infiltrate the cortex.4 Hence, the cellular components needed for the formation of a lesion such as meningioangiomatosis are in place.4 An alternate theory focuses on the meningothelial cell proliferation and would suggest that meningioangiomatosis represents a variant of meningioma.3–6,8 In this situation, meningioangiomatosis would represent a direct invasion of brain parenchyma by a leptomeningeal-based meningioma.4 Meningioangiomatosis does not represent a malignant neoplasm, and in contrast to a malignant meningioma, it is slow growing and has a relatively benign clinical course.3,4,8 Regardless of the underlying pathogenesis, it would appear that meningioangiomatosis represents a malformative or hamartomatous lesion. This is supported by the well-documented association of this lesion with NF1 and NF2, by the lesion's slow growth, and by its overall benign course.4 

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Author notes

Corresponding author: Richard A. Prayson, MD, Department of Anatomic Pathology (L25), Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195