Biology of hepatocellular neoplasia in the mouse. III. Electron microscopy of safrole-induced hepatocellular adenomas and hepatocellular carcinomas.

A systematic, ultrastructural analysis wsa performed on safrole-induced hepatocellular adenomas and hepatocellular carcinoma(s) (HPC) in BALB/c mice. Adenomas were heterogeneous in cell composition containing dark-staining basophilic cells, pale-staining acidophilic cells, clear cells, and lipid-laden cells. Darkly staining cells resembled fetal hepatocytes. They had large nuclei with irregular borders and limited diversity of organelles. Rough endoplasmic reticulum was prominent and seen as parallel cisternae in single or double tracts often in association with mitochondria. Pale-staining cells contained abundant smooth endoplasmic reticulum. Other organelles were often displaced to the perinuclear or peripheral region of the cell. The clear cells resembled dark-staining or pale-staining cells but also containing large areas of glycogen deposition. Lipid-laden cells contained numerous, multisized lipid droplets in the cytoplasm. HPC contained cell types similar to those of the adenoma. In addition, they contained many anaplastic cells. These resembled hepatocytes but contained several other alterations. The most striking was an apparent increase in the number of altered mitochondria. The cytoplasm was often fluid with enlarged mitochondria with dense or pale matrices. The cristae were few and had altered configurations. Also, an apparent increase was seen in the number of microbodies. These were often clustered in one region of the cytoplasm. An increase in microbodies was also noted in other cell types of hepatocellular carcinomas. The results of this study demonstrated similarities in the cell types of the adenomas and HPC. This study also demonstrated differences, with the anaplastic cell being common only to the carcinoma. Due to the similarity of cell types, the adenoma should be considered a possible site of HPC development.