From the Departments of Oncology and Biochemistry, St. Jude Children's Research Hospital, Memphis, TN
Authors’ disclosures of potential conflicts of interest are found at the end of this article.
Address reprint requests to Carlos Rodriguez-Galindo, MD, Department of Oncology, St. Jude Children's Research Hospital, 262 Danny Thomas Pl, MS 260, Room C-6009, Memphis, TN 38105; e-mail: carlos.rodriguez-galindo{at}stjude.org
Overview: Childhood adrenocortical tumors (ACTs) are very aggressive endocrine neoplasms whose incidence is quite low. Little is known about their pathogenesis, clinical presentation, and optimal treatment. In recent years, however, new information has been derived from the International Pediatric Adrenocortical Tumor Registry, and new clues to its pathogenesis have emerged. Germline TP53 mutation is almost always the predisposing factor in childhood ACTs. A unique germline mutation (TP53–R337H) has been described in Southern Brazil, where the incidence of ACT is 10 to 15 times the general incidence. Childhood ACTs typically present during the first 5 years of life and have female predominance. Hormone hyperproduction is almost universal, and most patients present with virilization. Surgery is the definitive treatment for ACTs, and a curative complete resection should always be attempted. Cisplatin-based chemotherapy with mitotane is indicated for unresectable or metastatic disease, although its impact on overall outcome is slight. In childhood ACTs, age, tumor size, and tumor resectability are the most important prognostic indicators. Outcome is stage-dependent; patients with small, resectable tumors have survival rates in excess of 80%, whereas the outcome for patients with unresectable disease is dismal. Patients with large, resectable tumors have an intermediate outcome. Childhood ACTs are rare, but their unique epidemiology appears to implicate novel oncogenic pathways that are unique to the pediatric population. Multiinstitutional and prospective studies are necessary to further our understanding of the pathogenesis and to improve outcomes.
