Subcellular abnormalities of liver sinusoidal lesions in human hepatocellular carcinoma

Liver sinusoidal lesions in 20 cases of human hepatocellular carcinoma (HCC) were examined with the electron microscope. Kupffer cells existed in the compact type of HCC. In area with pseudoglandular and trabecular cell patterns, Kupffer cells could not be observed. Only a few macrophages were distributed in the tumor tissues. Endothelial cells were altered and showed a poly-layered arrangement and were attached to each other with desmosome-like junctional complexes. There was a general loss of endothelial fenestrae. Endocytotic vesicles could be recognized in these endothelial cells. Poly-layered endothelial cells and accompanying layers of basal laminae were variably arranged between sinusoids and tumor cells with pseudoglandular, trabecular, or compact types of tumor cell patterns. Atypical cells containing numerous lysosomes, together with altered fat-storing (Ito) cells, were located in the tissue space bordering the capillaries. Moreover, tumor cells possessed flattened sinusoidal surfaces. These alterations of the sinusoidal wall suggest that capillarization of liver sinusoids in HCC took place, by loss of fenestrations, formation of basal laminae, and loss of microvilli on the surface of tumor cells. These architectural alterations are thought to completely change the physiological pattern of exchange of metabolites between tumor cells and the sinusoidal lumen. The absence of large numbers of Kupffer cells suggests that at this stage of tumor development, local cellular defense mechanisms were inoperative.