Light and Electron Microscopic Analysis of Liver Sinusoids during Hepatocarcinogenesis with 2‐Acetylaminofluorene in Rats

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Abstract
To clarify the sequential changes and morphological differences of the sinusoidal structures between hepatocellular carcinoma (HCC) and hepatocellular adenoma (HA), we examined morphological changes of sinusoidal cells and related structures such as basement membrane during hepatocarcinogenesis in the rat. During continuous feeding of carcinogenic diets containing 2‐acetylaminofluorene to rats, HA appeared at the 8th week in the periportal area and then extended toward the centrolobular area. The appearance of HCC was recognized at the 27th week. In the HA lesion, the morphology of sinusoidal cells and related structures was basically the same as that of normal liver except for a slight thickening of the basement membrane and a decreased amount of vitamin A‐lipid droplets of stellate cells. In HCC, the fenestrations of endothelial cells disappeared and the basement membrane became continuous, thick and often multilayered. Stellate cells contained almost no vitamin A‐lipid droplets and were associated with abundant collagen fibers. Kupffer cells and pit cells were not seen inside the sinusoid. All these features of the sinusoids in HCC resembled the morphological characteristics of the capillary. The present study has revealed that HCC possesses sinusoid structures distinct from those of HA. This suggests that HCC may not derive directly from HA but may develop newly within the HA.