Deletion of the NF2 Region in Both Meningioma and Juxtaposed Meningioangiomatosis: Case Report Supporting a Neoplastic Relationship

Abstract

We report a case of juxtaposed atypical meningioma and meningioangiomatosis (MA) in an 8-year-old boy with no clinical stigmata or family history of neurofibromatosis. We studied the proliferative activity and genetic changes in the two lesions in an attempt to define their biologic and pathogenetic relationships. The MIB-1 index was 11% in the meningioma and <1% in the MA, indicating increased proliferative activity in the meningioma. Fluorescence in situ hybridization was done for two chromosomal regions commonly deleted in meningiomas. There was loss of the neurofibromatosis 2 locus (22q12) in both the meningioma and MA. Conversely, the region of 1p32 was not deleted. Our results indicate that both the meningioma and MA arose from the same clonal process, with the meningioma probably undergoing additional, but undefined, genetic alterations that confer upon it a more proliferative potential. This loss of 22q12 in the MA raises doubt about the presumed hamartomatous nature of MA.

Cystic Meningioangiomatosis

“…Microscopically, nodules resembling meningioma was representative of our case. This finding may support previous reports describing concomitance of meningioma adjacent to MA [3, 4]. …”

Sporadic meningioangiomatosis with and without meningioma: analysis of clinical differences and risk factors for poor seizure outcomes

“…This finding suggests that, as an endothelial cell marker to detect microvascular proliferation activity, CD34 could be used as an ancillary method for identifying sporadic MA. As a proliferation index, Ki-67 was consistently low in MA; however, all of the literature pertaining to Ki-67, as well as our cases, has found that Ki-67 is higher in the meningioma component than in the MA portion [3][4][5]61]. One reasonable explanation is that meningioma arises from the MA component with an Overall, the pathogenesis of MA is unclear.…”

“…However, a few cases have shown loss of heterozygosity on 22q12 and 9p21, raising the possibility of a neoplastic nature [3,72]. For MA-M, meningiomaassociated genetic alterations have always been found in both the MA and meningioma components, substantiating the neoplastic nature of MA-M [3][4][5]. Based on the aforementioned genetic studies, we postulate that pure MA and MA-M have distinct biological natures, with pure MA lesions more similar to non-neoplastic lesions and MA-M more similar to neoplastic lesions, which can result in different clinical features.…”

“…A presumed hamartomatous or non-neoplastic nature is favored by its typically benign clinical course and the absence of marked proliferation activity in most cases [15]. For pure MA, genetic studies have supported that the majority of pure MA lesions are non-neoplastic, based on no evidence of NF2 gene deletions [4,5,84]. However, a few cases have shown loss of heterozygosity on 22q12 and 9p21, raising the possibility of a neoplastic nature [3,72].…”

“…Occasionally, sporadic MA combines with a neoplasm, most commonly meningioma (MA-M) [2]. MA is usually considered a benign, nonneoplastic lesion, while genetic and molecular studies have suggested that MA-M may be a neoplasm [3][4][5]. Given the neoplastic nature of MA-M, it is reasonable to assume that the clinical features of MA-M may be different from those of pure MA.…”