Ultrastructural and Immunocytochemical Characterization of the Cellular Phenotype in Primary Adenoid Liver Tumours of the Rat

The cellular phenotype of 34 primary adenoid liver tumours induced in rats with N-nitrosomorpholine was studied by immunocytochemical and electron microscopical methods in order to elucidate the histo- and cytogenesis of these tumours. Three types of ducts were distinguished in the adenoid liver tumours at the ultrastructural level being characterized as of hepatocellular, transitional and cholangiocellular phenotype. The transitional cells took an intermediate position between the hepatocellular and the cholangiocellular phenotype. Frequent features of the hepatocyte-like differentiation were large round nuclei with a dispersed chromatin, glycogen-associated ER complexes, peroxisomes and the formation of bile canaliculi. Evidence for the relationship to bile ductular cells was provided by the regular association with a basement membrane, the (inconstant) positive immunohistochemical reaction for cytokeratin polypeptide KA-4, a poorly developed ER and small mitochondria. An additional finding in the ducts with a transitional cellular phenotype was the selective accumulation of mast cells integrated into the epithelium. Intimate associations between cells of the hepatocellular, transitional and cholangiocellular phenotype were observed at the light and electron microscopic level. The results suggest that a transdifferentiation (metaplasia) from cells with a hepatocellular to those with a transitional or cholangiocellular phenotype takes place in many liver tumours.