Abstract C013: The spectrum of nephrogenic rests in children with cancer predisposition syndromes

Abstract

Nephrogenic rests (NR) are foci of abnormal embryonal renal tissue that persist beyond fetal development and are recognized as potential precursor lesions of Wilms tumor. Perilobar NRs are associated with Beckwith-Wiedemann syndrome (BWS), however NRs have not been stratified by BWS molecular subtype. Imaging characteristics used to distinguish NRs from small Wilms tumors were developed in non-syndromic, perilobar-predominant cohorts and may not be applicable in patients with predisposition syndromes. We conducted a multi-institutional, retrospective analysis in 44 children with NRs and a cancer predisposition syndrome (29 BWS, 10 WAGR, 3 Perlman syndrome, 2 WT1-related Wilms tumor predisposition). NRs were defined as lesions that were suspected radiologically and/or confirmed pathologically to be NRs and were classified by their location (perilobar, intralobar, combined), hyperplastic nature on pathology, and by molecular subtype in BWS. We also descriptively analyzed the potential malignant transformation of NRs as well as how they responded to chemotherapy on serial imaging. Patients with gain of methylation at imprinting cluster one (IC1 GOM) were the most common subtype of BWS with NRs. Although perilobar NRs were more common in BWS, two patients with BWS-IC1 GOM had pathologically confirmed intralobar NRs without the presence of perilobar NRs which has not previously been reported. Among the 10 patients with WAGR syndrome, five patients who underwent partial nephrectomies for suspected Wilms tumor were ultimately found to have intralobar NRs rather than Wilms tumor on pathology. Given the elevated risk of developing chronic kidney disease in WAGR syndrome, this observation has important implications for surveillance and decisions to treat versus observe small renal lesions in children with WAGR syndrome. Our study provides the subtype level stratification of NRs in BWS and reports on the high rate of NR misclassification for Wilms tumor in WAGR syndrome.