Pediatric adrenal cortical carcinomas: Histopathological criteria and clinical trials. A systematic review

Adrenal tumors are quite rare in infancy and childhood with the exception of neuroblastoma. In fact, adrenocortical tumors (ACT) account for only 0.2% of all malignant cancers in children and adolescents. According to a multicenter registry investigation, the median interval between first endocrine symptoms and the diagnosis of ACT is 5 months, and death is seen in 38% of patients, who suffer from tumor progression following the diagnosis in about 2½ years. The prognosis of pediatric ACC is poor with a 5-year event-free survival of 54%. To face this dreadful scenario, a few decades ago the International Pediatric Adrenocortical Tumor Registry (IPACTR) was established. Moreover, Children's Oncology Group (COG) and National Cancer Institute (NCI) have approved several clinical trials designed to investigate new treatment options in pediatric ACT. In this systematic review, we summarize the diagnostic histopathologic criteria, bio-markers, and clinical trials of this challenging diagnosis. Eleven pediatric ACT trials were reviewed in our investigation. Two out of 11 studies were conducted in Brazil showing apparently an increased rate of germline mutation-related pediatric ACT. A heterogeneous methodology was evident with four non-randomized clinical trials, three prospective cohort studies, and four retrospective case-control studies limiting higher statistical approach. Tumor histology remains the backbone to diagnose ACT creating a common investigative platform and potentially supporting studies aiming to increase international collaborative research, which is crucial for this challenging disease.