Bilateral Wilms tumour: a review of clinical and molecular features

Abstract

Wilms tumour (WT) is the most common paediatric kidney cancer and affects approximately one in 10 000 children. The tumour is associated with undifferentiated embryonic lesions called nephrogenic rests (NRs) or, when diffuse, nephroblastomatosis. WT or NRs can occur in both kidneys, termed bilateral disease, found in only 5-8% of cases. Management of bilateral WT presents a major clinical challenge in terms of maximising survival, preserving renal function and understanding underlying genetic risk. In this review, we compile clinical data from 545 published cases of bilateral WT and discuss recent progress in understanding the molecular basis of bilateral WT and its associated precursor NRs in the context of the latest radiological, surgical and epidemiological features.

Figure 1.

Bilateral Wilms tumour (BWT) is frequently associated with germline genetic or epigenetic aberrations. During kidney development, kidney precursor cells undergo mesenchymal to epithelial transition (MET) to form the epithelial structures of the normal kidney (light orange). In cases where cells carry germline aberrations (but not in every case), normal development is disrupted and retained embryonic tissue is found in the normal kidney (nephrogenic rests; dark orange). Intralobar nephrogenic rests (ILNR) are associated with WT1 mutation and perilobar nephrogenic rests (PLNR) are associated with 11p15 loss of imprinting (LOI). These lesions are considered precursors to Wilms tumour and are found in nearly all cases of bilateral Wilms tumour (BWT; dark red) although the molecular mechanisms involved in transformation are unknown. Mutation of CTNNB1 is likely to be a secondary event following germline WT1 mutation. Further late events are acquired over the progression of the tumour. Shown in black are several reported germline aberrations found in patients with BWT, however the genetic background is not always known and BWT could also arise from somatic mutation in each kidney.

Figure 2.

MRI images of bilateral nephroblastomatosis enhancing the diffuse homogeneity and the rind-like peripheral location of the lesions (a) compared with the heterogeneity and round shape of bilateral WT (b). The left kidney seems suitable to a nephron sparing surgery as the mass arises from the superior pole above the left pedicle (b). Corresponding apparent diffusion coefficient (ADC) maps demonstrate low ADC in both kidneys with nephroblastomatosis (c) but different ADC values between the right solid nephroblastoma and the left cystic tumour (d).