Adrenocortical tumors associated with the TP53 p.R337H germline mutation can be identified during child-care consultations.

ABSTRACT

OBJECTIVE: To evaluate the clinical features associated with adrenocortical hormone overexpression and familial cancer profiling as potential markers for early detection of adrenocortical tumors in children from South and Southeast Brazil. METHODS: The clinical manifestations and anthropometric measurements of 103 children diagnosed with adrenocortical tumors were analyzed. RESULTS: Between 1982 and 2011, 69 girls and 34 boys diagnosed with adrenocortical tumors were followed-up for a median time of 9.0 years (0-34 years). Signs of androgen overproduction alone (n=75) or associated with cortisol (n=18) were present in 90.3%. TP53 p.R337H mutation was found in 90.5% of patients. Stages I, II, III, and IV were observed in 45.6%, 27.2%, 19.4%, and 7.8% of patients, respectively. At diagnosis, there were no significant differences in height (p=0.92) and weight (p=0.22) among children with adrenocortical tumors, but children with virilization alone had significantly higher height-for-age Z-scores (0.92±1.4) than children with hypercortisolism alone or combined (-0.32±1,8; p=0.03). The five-year overall survival was 76.7% (SD±4.2). Patients with advanced-stage disease had a significantly worse prognosis than those with limited disease (p<0.001). During follow-up, ten of 55 p.R337H carrier parents developed cancer, whereas none of the 55 non-carriers did. CONCLUSIONS: Signs of adrenocortical hormone overproduction appear early, even in cases with early-stage. These signs can be identified at the physical examination and anthropometric measurements. In southern Brazil, pediatric adrenocortical tumor is a sentinel cancer for detecting families with germline p.R337H mutation in TP53 gene.