Abstract
Cystic degeneration (CD) in the liver is a cyst-like lesion composed of one or more pseudocysts lacking lining cells, occurring spontaneously in rats older than 12 months, with a male predilection. In this study, 32 CDs were identified in 23 out of 104 non-treated, control male Sprague-Dawley rats from two combined chronic toxicity and carcinogenicity studies with agrochemicals. They were examined histologically, histochemically, and immunohistochemically to assess the pathogenesis and pathological significance of CD, focusing on pseudocapillarization in aged rat liver. Pseudocapillarization refers to age-related capillarization of hepatic sinusoids and is distinct from sinusoidal capillarization observed in hepatic cirrhosis. Both CD and pseudocapillarization, characterized by factor VIII-related antigen expression, were primarily noted in the periportal regions of the rat liver. CD areas exhibited enhanced vimentin expression in a diffuse linear pattern in their septa with occasional focal linear α-smooth muscle actin expression and the fluid containing hyaluronic acid accumulated in their lumen that are thought to be formed by hepatocellular apoptosis. These findings suggest a series of reactive changes associated with hepatocellular apoptosis due to pseudocapillarization in the sinusoids. In conclusion, spontaneous CD in rat liver is not a degenerative lesion or cystic enlargement of stellate cells, but a structural abnormality in pre-existing liver tissue resulting from aging-related changes in sinusoidal endothelial cells and hepatocytes. Pseudocapillarization of sinusoids is considered a precursor lesion of CD in the rat liver.