Histopathological and Molecular Characteristics of Wilms Tumor

ABSTRACT

Diagnosis of malignant renal tumors does not mostly create difficulties. Although micrometastases may be encountered during postmortem examination, kidney is not a preferred organ for clinically detected metastases of malignant tumors. Therefore, almost all renal tumors in adults and children are primary tumors. When primary renal tumors are encountered, most of the cases pose a diagnostic simplicity. Indeed, diagnosis of malignant kidney tumors in children is Wilms tumor (WT) in 80–90% of the cases, while it is renal cell carcinoma in adults. In fact, a typical WT contains tissue components in three different morphologies. These are mesenchymal component resembling primitive fetal mesenchyme, epithelial component that reminds us fetal renal tubules and glomeruli, and blastomatous component consisting of clusters of blast cells that contributed to the coinage of the term “nephroblastoma.” However, not all WTs are triphasic, and different tissue components in very restricted areas may be overlooked. Besides, immunohistochemical staining methods helpful in the differential diagnosis of other tumors are not much useful in WT. Embryonic development of kidney is a complex process in which different transcription factors, proto-oncogenes, and various types of growth factors are effective. WT can be considered a failure of this transition. A number of genes are involved in nephrogenesis, as well as in Wilms tumorigenesis. Recently, some of these genes are believed to be regulated by HACE1, glypican 3 (GPC3), and six WT genes. The incidence of WT is 1:10,000 worldwide. Currently, high cure rates can be achieved, and multimodality treatment has resulted in a significant improvement in outcomes. In this chapter, histopathological features of WT, genetic and molecular modifications related to WT, the effects of these genetic abnormalities on prognosis, and clues for differential diagnosis were evaluated.