Familial Wilms' tumor with neural elements: Characterization by histology,immunohistochemistry, and genetic analysis

Wilms' tumor (WT) is the most common renal malignancy of children. While mo st occur sporadically, a small percentage are familial or occur as part of a developmental syndrome. Classic WTs exhibit a triphasic histologic patter n composed of blastema, epithelium, and stroma. Occasionally, heterologous elements may also be observed. In this study we investigated a series of fo ur WTs that occurred within a single familial aggregate and contained focal areas of neural differentiation. The tumors were evaluated histologically for the presence of neural elements and immunohistochemically for expressio n of neural-related markers. Genetic linkage analysis was performed on 3 of the 4 WTs. In addition to the classic triphasic histology, the WTs contain ed tumor rosettes (4/4), ganglion cells (2/4), foci of ganglioneuromatous d ifferentiation (2/4), and anaplasia (1/4). Staining for chromogranin, S-100 , synaptophysin, vimentin, and neuron-specific enolase was positive in all 4 tumors within the areas of neural differentiation whereas staining for CD 99 (013) and glial fibrillary acidic protein was negative. Linkage analysis studies suggest that the familial predisposition gene segregating in this family is at 19q13.4. To our knowledge, this is the first reported series o f WTs with neural differentiation that occurred within a single family aggr egate. Genetic linkage analysis of this family is consistent with linkage t o the FWT2 WT predisposition gene at 19q13.4. We propose that these tumors may represent a unique manifestation of tumor susceptibility in this family .