Adrenocortical Tumors in Children

Abstract

Childhood adrenocortical carcinoma (ACC) is rare; only 25 cases are expected to occur annually in the United States. Internationally, however, its incidence varies; it is 10–15 times higher in Southern Brazil. Germline TP53 mutations have been implicated in 50–65% of cases generally and in 95% of cases in Brazil, where the TP53p.R337H variant is prevalent. Children with ACC present typically in the first 5 years of life, with a strong female predominance, and almost universally with virilization. Biologically, childhood ACC has distinctive features; its genomic landscape is characterized by copy-neutral loss of heterozygosity (LOH) of chromosomes 11 and 17 associated with germline TP53 pathogenic variants, universal IGF2 overexpression, and somatic mutations in ATRX and CTNNB1. Surgery is the mainstay of therapy, and for children with advanced disease, chemotherapy and mitotane are indicated. Low stage and complete resection are the most important prognostic factors; more than 90% of patients with small, localized tumors are long-term survivors, compared with 10% of those with metastatic disease. Despite complete tumor resection, disease recurs in 50% of patients with large, localized tumors, where tumor spillage is common. Future clinical studies should focus on risk-adapted therapies that incorporate clinical and biological features.