Meningiomas may be a component tumor of multiple endocrine neoplasia type 1

Purpose: Recently, an increased incidence of some non-endocrine tumors are reported in patients with multiple endocrine neoplasia type I (MEN 1). There are rare reports of meningiomas and other central nervous system tumors in these patients, but it is unknown if they are more frequent or if allelic loss of the MEN] gene is important in their pathogenesis. The aim of this study was to address these two latter questions. Experimental Design: Results from a prospective study of 74 MEN 1 patients with suspected/proven pancreatic endocrine tumors (PETs) were analyzed, as well as molecular studies performed on a resected meningioma. All patients had serial brain imaging studies (computed tomography, magnetic resonance imaging, and octreoscanning since 1994) and yearly studies evaluating MEN 1 involvement with a mean follow-up of 7.2 years. Results were compared with 185 patients with sporadic Zollinger-Ellison syndrome. Results: Six patients (8%) had meningiomas. Meningiomas were single and found late in the MEN 1 course (mean age = 51 years). Magnetic resonance imaging/computed tomography were more sensitive than octreoscanning. Their diagnosis averaged 18 years after the onset of hyperparathyroidism, 10-15 years after pituitary disease or PETs. Meningiomas were 11 times more frequent in patients with PETs with MEN I than without MEN 1 (P = 0.017). No clinical, laboratory, or MEN I feature distinguished patients with meningiomas. Meningiomas were asymptomatic and 60% showed no growth. A resected meningioma showed loss of heterozygosity at 11q13 and 1p, including at p73 and ARHI/NOEY2 locus, but not at the neurofibromatosis 2 gene locus. Conclusions: These results show meningiomas are not an infrequent occurrence in MEN 1, and loss of the function of the MEN1 gene product plays a role in their pathogenesis in these patients.