The nephroblastomatosis complex and its relationship to Wilms' tumor: a clinicopathologic treatise

1. At least one third of all children with Wilms' tumors have evidence of aberrant metanephric differentiation, hamartomas, adenomas and nodules of blastema or Wilms' tumorlets in the subcapsular renal cortex. Only the presence of nodular renal blastema was found to correlate with younger age, suggesting that the other tumorlike lesions may be derivatives. 2. In our experience, all patients with bilateral and sequential bilateral Wilms' tumors have exhibited these characteristics in the "uninvolved" renal tissue removed at nephrectomy. 3. Pancortical (infantile), diffuse superficial (late infantile) and multifocal (juvenile) variants of nephroblastomatosis are defined. In the latter 2 forms of nephroblastomatosis the prognosis after modern therapy is at least as good as it is in patients with unilateral, unicentric Wilms' tumor arising in a histologically normal kidney. 4. The morphologic evidence presented strongly indicates that Wilms' tumor in patients with nephroblastomatosis develops either from nodular blastema or metanephric hamartomas. It is hypothetically possible that all Wilms' tumors develop from these precursors. The latent period between cessation of nephrogenesis and clinical presentation of Wilms' tumor is interpreted as favoring the hypothesis that carcinogenesis per se is the result of a postnatal event but that the substrate for tumor development, aberrant metanephric proliferation, has its inception during gestation.