Hepatocarcinomas, cholangiocarcinomas, and hepatoblastomas produced by chemically transformed cultured rat liver epithelial cells. A light- and electron-microscopic analysis.

The histology and ultrastructure of more than 100 tumors produced by a chemically transformed rat liver epithelial cell line and its single-cell-derived clonal subpopulations were studied. Wide-ranging morphologic presentations were observed, including carcinomas, sarcomas, "mixed epithelial-mesenchymal" tumors, and undifferentiated tumors. In addition to epidermoid and adenocarcinomas, several tumors were morphologically indistinguishable from hepatocellular carcinomas. The "mixed epithelial-mesenchymal" tumors reproduced most of the various histologic features of human hepatoblastomas. In many instances, the epithelial component occupied focal areas of tumors, and transmission electron microscopic studies of the "sarcomatous" regions revealed either spindle-shaped epithelial tumor cells or, in most cases, scattered epithelial tumor cells surrounded by numerous fibroblasts or myofibroblasts. Similar findings were observed in several "sarcomas" examined ultrastructurally, which suggests that most of the mixed tumors or sarcomas actually were spindle cell carcinomas and/or carcinomas with marked host fibroblastic reaction. However, in a few mixed tumors produced by clonally derived cell strains, unequivocal carcinosarcomas with neoplastic osteoid or chondroid tissue were demonstrated. The findings of this study are discussed in the context of current insights on the cellular composition of the liver and on the histogenesis of human hepatoblastoma.