Light and electron microscopic comparisons of normal hepatocytes and neoplastic hepatocytes of well-differentiated hepatocellular carcinomas in a teleost fish

Well-differentiated hepatocellular carcinomas (HCC's) induced in the sheepshead minnow Cyprinodon variegatus w ~ t h N-nitrosodiethylamine perm~tted light microscop~cal and ultrastructural comparisons of normal hepatocytes and adjacent HCC cells. Normal hepatocytes contained typical organelles with their intracellular distribution similar to that described for other teleosts. These cells revealed a strong compartmentalization of organelles consisting of restricted perinuclear cytoplasm containing rough endoplasmic reticulum (RER) and mitochondria; most of the rest of the cell's cytoplasm volume was filled with P-glycogen particles. Adjacent HCC cells at the border of the neoplasm interdigitated (invaded) between normal hepatocytes and replaced normal hepatocytes close to the HCC edge and adjacent to the bile canaliculi. Within the HCC, cells had little intercellular space between them and atypical bile canaliculi were found occasionally between adjacent hepatocytes. The HCC cells appeared to differ mainly in a quantitative, rather than in a qualitative fashion, and in the distribut~on of organelles from normal hepatocytes. HCC cells were not compartmentalized; their organelles (RER and mitochondria) were distributed throughout the cytoplasm, and only small amounts of glycogen remained diffusely distnbuted or in small masses or foci. Mitochondrial intermembrane myelin bodies (MMB's) were found frequently in the HCC cells but less frequently in the normal hepatocytes. Some cells at the edge of the HCCs appeared to be intermediate between inner HCC cells and normal hepatocytes in terms of abundance and distribution of organelles and glycogen. The possible significance of the MMB's and intermediate, edge cells is discussed, as well as the need to better characterize features of well-differentiated hepatic neoplasms in order to assure their proper inclusion in neoplasm incidence/prevalence data in fish carcinogenesis assays and field studies.