Adrenocortical carcinoma in patients with MEN1: a kindred report and review of the literature.

Objective: Up to 40% of multiple endocrine neoplasia type 1 (MEN1) patients may have adrenal cortical tumors. However, adrenocortical carcinoma (ACC) is rare. The clinical manifestations, prevalence, inheritance and prognosis of ACC associated with MEN1 remain unclear. Here we report the clinical manifestations and prevalence of ACC in patients with MEN1. Design and methods: A retrospective analysis of ACC associated with MEN1 patients at a single tertiary care center from December 2001 to June 2017. Genetic analysis of MEN1 and other ACC associated genes, loss of heterozygosity (LOH) of MEN1 locus, immunohistochemistry staining of menin, P53 and beta-catenin in ACC tissue were performed. Results: Two related patients had ACC associated with MEN1. The father had ENSAT stage IV tumor with excessive production of cortisol; the daughter had nonfunctional ENSAT stage I tumor. Both patients carried novel germline heterozygous mutation (c. 400_401insC) of MEN1. The wild-type MEN1 allele was lost in the resected ACC tissue from the daughter with no menin staining. The ACC tissue had nuclear beta-catenin staining, with heterozygous CTNNB1 mutation of 357del24 and P53 staining in only 20% cells. Conclusions: ACC associated with MEN1 is rare and may occur in familial aggregates.