Diseases Predisposing to Adrenocortical Malignancy (Li-Fraumeni Syndrome, Beckwith-Wiedemann Syndrome, and Carney Complex)

Adrenocortical malignancies can occur in the context of several tumor predisposition syndromes.The Carney complex (CNC) is responsible for the majority of primary pigmented nodular adrenal diseases and is more rarely associated with adrenocortical carcinoma (ACC). Other core manifestations of CNC include cardiac and cutaneous myxomas, lentiginosis, somatotroph pituitary adenomas, Sertoli tumors, melanocytic schwannoma, and thyroid, breast, and bone tumors. CNC is mostly due to germline inactivating mutations of PRKAR1A.The majority of childhood ACC are related to genetic predisposition. The Beckwith-Wiedemann syndrome (BWS) is an overgrowth and tumor predisposition syndrome due to genetic or epigenetic alterations at the 11p15 locus. Classical tumor spectrum of BWS includes embryonal tumors and childhood ACC. The Li-Fraumeni syndrome (LFS) is a devastating tumor predisposition syndrome, due to germline inactivating mutations of TP53, and characterized by a high, various, and early-onset cancer risk. LFS spectrum includes premenopausal breast cancer, soft-tissue sarcoma, osteosarcoma, central nervous system tumor, and ACC, accounting for 50-80% of pediatric cases. Finally, germline predisposition affects up to 10% of adult ACC patients, mostly in part of LFS and Lynch syndrome.This chapter focuses on the diagnosis, screening, and management of adrenal tumors in part of these tumor predisposition syndromes.