[Histogenesis of hepatoblastoma. Morphological, immunoelectron microscopic and immunohistochemical findings]

The wide range of epithelial and mesenchymal lines of differentiation seen in hepatoblastoma suggests that this tumor derives from a pluripotent stem cell. In order to test this hypothesis, seven hepatoblastomas of various subtypes were investigated for the presence of cells with the features of the oval cells found during hepatocarcinogenesis in rodents that are thought to be closely related to hepatic stem cells. The specimens were investigated by electron microscopy, electron microscopic immunocytochemistry, and immunohistochemical staining for cytokeratins nos. 7, 8, 18, and 19. Small epithelial cells (SEC) corresponding to the oval cells of the rat and the "small cells" found in human liver disease with chronic ductular reaction, both of which are thought to be related to hepatic stem cells, were found. The SEC were oval and exhibited intercellular junctions, tonofilament bundles, and a biliary epithelium-type cytokeratin profile. They were found in small numbers in fetal hepatoblastoma and in moderate numbers in embryonal hepatoblastoma. In small cell hepatoblastoma, nearly all the tumor cells exhibited SEC-like ultrastructural features and a corresponding cytokeratin profile. Thus, cells with the features of hepatic stem cells are detectable in hepatoblastoma. Their numbers vary according to the subtype, reflecting the differing degrees of differentiation of the various subtypes, consistent with the theory propounded in the literature that embryonal and, with further differentiation, fetal tumor cells derive from precursor small cells. The findings support the hypothesis that hepatoblastoma derives from a pluripotent, probably entodermal or even less committed, stem cell.