Scanning electron microscopy of experimentally induced hepatocellular carcinoma.

Hepatocellular carcinomas (HCC) induced in rats by diethylnitrosamine were observed by light microscopy (LM) and scanning electron microscopy (SEM). Liver cirrhosis did not develop. The tumors were of 4 types; trabecular, glandular, adenoid and hyperplastic nodular (HN). SEM demonstrated that trabecular lesions were packed with many layers of HCC cells which had in some places bile canaliculi on the intercellular surfaces with sparse microvilli. Glandular lesions were composed of gland-like structures having columnar or cuboidal cells with numerous microvilli on the hemispherical apex. Glandular lumens were bordered from intercellular spaces by the zona occludens. The glandular structures were derived from the exterior of the trabecular lesions and were closed at both ends, as confirmed by reconstruction of serial sections. Adenoid lesions, which had gland-like structures in the trabecula, were often observed between purely trabecular and purely glandular lesions. HN-type lesions composed of two-cell-thick plates were mostly located at the peripheral parts of the HCC tumor and were continuous with other lesions. HN-type lesions had markedly dilated bile canaliculi and well-developed microvillous projections on the intercellular surfaces. The HN-type lesions had structures similar to those of late HN. The existence of lesions indistinguishable from late HN in the periphery of HCC tumors indicates the HCC develop from HN. In summary, the rat HCC were of 4 types of lesions which had characteristic histological and cytological structures, but which were connected with each other, changing gradually from one to the other.