Although most patients with a histologic diagnosis of Wilms tumor fare well with current treatment, approximately 10% of patients have histopathologic features that are associated with a poorer prognosis, and in some types, with a high incidence of relapse and death. Wilms tumor can be separated into three prognostic groups on the basis of histopathology-favorable histology, anaplastic histology, and nephrogenic rests.
Histologically, Wilms tumor mimics development of a normal kidney consisting of three cell types: blastemal, epithelial (tubules), and stromal. Not all tumors are triphasic, and monophasic patterns may present diagnostic difficulties. While associations between histologic features and prognosis or responsiveness to therapy have been suggested, with the exception of anaplasia, none of these features have reached statistical significance and therefore do not direct the initial therapy.
Anaplastic histology accounts for about 10% of Wilms tumors. Anaplastic histology is the single most important histologic predictor of response and survival in patients with Wilms tumor. There are two histologic criteria for anaplasia, both of which must be present for the diagnosis. They are the presence of multipolar polyploid mitotic figures with marked nuclear enlargement and hyperchromasia. Mutations in the p53 gene have been associated with anaplastic histology. Anaplasia correlates best with responsiveness to therapy rather than to aggressiveness. It is most consistently associated with poor prognosis when it is diffusely distributed and when identified at advanced stages. These tumors are more resistant to the chemotherapy traditionally used in children with favorable-histology Wilms tumor. This is the reason why focal anaplasia and diffuse anaplasia are differentiated, both pathologically and therapeutically. Focal anaplasia is defined as the presence of one or a few sharply localized regions of anaplasia within a primary tumor. Focal anaplasia does not confer as poor a prognosis as does diffuse anaplasia.[3,4,5]
Nephrogenic rests are abnormally retained embryonic kidney precursor cells arranged in clusters. Nephrogenic rests are found in about 1% of unselected pediatric autopsies, 35% of kidneys with unilateral Wilms tumors, and in nearly 100% of kidneys with bilateral Wilms tumors.[6,7] The term nephroblastomatosis is defined as the presence of diffuse or multifocal nephrogenic rests. There are two types: intralobar nephrogenic rests and perilobar nephrogenic rests. Diffuse hyperplastic perilobar nephroblastomatosis is defined as nephroblastomatosis forming a thick rind around one or both kidneys and is considered a preneoplastic condition. Patients with any type of nephrogenic rest in a kidney removed for nephroblastoma should be considered at increased risk for tumor formation in the remaining kidney. This risk decreases with patient age. Extrarenal nephrogenic rests rarely occur, but may develop into extrarenal Wilms tumor.
Clear Cell Sarcoma of the Kidney
Clear cell sarcoma of the kidney (CCSK) is not a Wilms tumor variant, but it is an important primary renal tumor associated with a significantly higher rate of relapse and death than favorable-histology Wilms tumor. In addition to pulmonary metastases, clear cell sarcoma also spreads to bone, brain, and soft tissue. The classic pattern of CCSK is defined by nests or cords of cells separated by regularly spaced fibrovascular septa. Previously, relapses have occurred in long intervals after the completion of chemotherapy (up to 10 years), however with current therapy relapses after 3 years are uncommon. The brain is a frequent site of recurrent disease.[12,13]