SMALL EPITHELIAL-CELLS AND THE HISTOGENESIS OF HEPATOBLASTOMA - ELECTRON-MICROSCOPIC, 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 pluripo tent stem cell. To test this hypothesis, seven hepatoblastomas of vari ous subtypes were investigated for the presence of cells with the feat ures of the oval cells found during hepatocarcinogenesis in rodents th at are thought to be closely related to hepatic stent cells. Because s imilar cells, referred to as ''small cells,'' have been described in h uman liver disease with chronic ductular reaction, five liver biopsies front infants with biliary atresia were also investigated The specime ns were investigated by electron microscopy, immunoelectron microscopy , and immunostaining for cytokeratins 7, 8, 18, and 19. Small epitheli al cells (SEC) corresponding to the oval cells of the rat and the ''sm all cells'' in humans were found in both biliary atresia and hepatobla stoma. These cells were oval and exhibited intercellular junctions, to nofilament bundles, and a biliary epithelium-type cytokeratin profile. SEC were found in small numbers in fetal hepatoblastoma and in modera te 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 exhibiting morph ological and immunophenotypic features of hepatic stem cells are detec table in hepatoblastoma. Their numbers vary according to the subtype, reflecting the differing degrees of differentiation of the various sub types, consistent with the theory propounded in the literature that em bryonal and, with further differentiation, fetal tumor cells derive fr om precursor small cells. The findings support the hypothesis that hep atoblastoma derives from a pluripotent, probably entodermal or even le ss committed, stem cell.