Newborn Screening for the Detection of the TP53 R337H Variant and Surveillance for Early Diagnosis of Pediatric Adrenocortical Tumors: Lessons Learned and Way Forward

SIMPLE SUMMARY: Adrenocortical tumor (ACT) is rare in children and fatal if not detected early. Children who inherit a mutation of the TP53 gene tend to develop ACT early in life. In the 1990s, scientists revealed that a TP53 variant (R337H) was frequent in South Brazil. Therefore, the incidence of ACT in children is 20 times higher in this region than in other countries. We reviewed the records of 16 children with ACT treated in a pediatric hospital in Parana state (southern Brazil) and 134 children registered in the state public registry data. We found a high number of cases with advanced disease, leading to an unacceptable number of deaths. These observations contradict newborn R337H screening and surveillance data, showing that surgical intervention in early cases of ACT is associated with a 100% cure. Newborn screening/surveillance should be implemented in regions with a high frequency of the R337H variant. ABSTRACT: The incidence of pediatric adrenocortical tumors (ACT) is high in southern Brazil due to the founder TP53 R337H variant. Neonatal screening/surveillance (NSS) for this variant resulted in early ACT detection and improved outcomes. The medical records of children with ACT who did not participate in newborn screening (non-NSS) were reviewed (2012–2018). We compared known prognostic factors between the NSS and non-NSS cohorts and estimated surveillance and treatment costs. Of the 16 non-NSS children with ACT carrying the R337H variant, the disease stages I, II, III, and IV were observed in five, five, one, and five children, respectively. The tumor weight ranged from 22 to 608 g. The 11 NSS children with ACT all had disease stage I and were alive. The median tumor weight, age of diagnosis, and interval between symptoms and diagnosis were 21 g, 1.9 years, and two weeks, respectively, for the NSS cohort and 210 g, 5.2 years, and 15 weeks, respectively, for the non-NSS cohort. The estimated surveillance/screening cost per year of life saved is US$623/patient. NSS is critical for improving the outcome of pediatric ACT in this region. Hence, we strongly advocate for the inclusion of R337H in the state-mandated universal screening and surveillance.