Pediatric Adrenocortical Carcinoma: The Nuts and Bolts of Diagnosis and Treatment and Avenues for Future Discovery

Allison F O’Neill,1 Raul C Ribeiro,2 Emilia M Pinto,3 Michael R Clay,4 Gerard P Zambetti,3 Brent A Orr,3 Christopher B Weldon,5 Carlos Rodriguez-Galindo2,6 1Department of Pediatric Oncology, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA, USA; 2Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA; 3Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN, USA; 4Department of Pathology, Children’s Hospital Colorado, Denver, CO, USA; 5Department of Surgery, Boston Children’s Hospital, Boston, MA, USA; 6Department of Global Pediatric Medicine, St. Jude Children’s Research Hospital, Memphis, TN, USACorrespondence: Allison F O’Neill, Department of Pediatric Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue – DA3111, Boston, MA, 02215, USA, Email [email protected]: Adrenocortical tumors (ACTs) are infrequent neoplasms in children and adolescents and are typically associated with clinical symptoms reflective of androgen overproduction. Pediatric ACTs typically occur in the context of a germline TP53 mutation, can be cured when diagnosed at an early stage, but are difficult to treat when advanced or associated with concurrent TP53 and ATRX alterations. Recent work has demonstrated DNA methylation patterns suggestive of prognostic significance. While current treatment standards rely heavily upon surgical resection, chemotherapy, and hormonal modulation, small cohort studies suggest promise for multi-tyrosine kinases targeting anti-angiogenic pathways or immunomodulatory therapies. Future work will focus on novel risk stratification algorithms and combination therapies intended to mitigate toxicity for patients with perceived low-risk disease while intensifying therapy or accelerating discoveries aimed at improving survival for patients with difficult-to-treat disease.Keywords: adrenocortical, pediatric, management, discovery, carcinoma, tumors