To identify Ito cells in normal and pathological adult human livers, immunohistochemical studies were performed by the avidin-biotin-peroxidase complex method using monoclonal antibodies for alpha-smooth muscle actin (ASMA), desmin, and vimentin. Fifty one needle biopsies, 7 surgically resected specimens, and 5 autopsy specimens were studied. In the normal adult liver vascular smooth muscle cells and pericytes, together with perisinusoidal cells with thin cytoplasmic processes were positive for ASMA. These latter cells formed a loose and discontinuous layer along the sinusoidal walls. Immunoelectron microscopy showed that the ASMA-positive perisinusoidal cells were Ito cells containing fat droplets. The other sinusoidal lining cells were negative for ASMA. In chronic liver disease, ASMA-positive Ito cells showed an increase in number, size, and the intensity of immunostaining in areas of piece-meal necrosis), and formed a continuous cellular network. These cells were dendritic in shape with irregularly elongated cytoplasmic processes and contained an increased amount of microfilaments, in association with loss of the characteristic fat droplets. Thus, their ultrastructural features corresponded to those of myofibroblastic cells. Ito cells showed no staining for desmin in both normal and pathological livers. These results indicate that immunohistochemistry using an anti-ASMA antibody is a sensitive and reliable method for the identification of both normal and transformed Ito cells in adult human livers.

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It is conceivable that the carcinomatous and sarcomatous components grow separately from the early stage of the tumors, and that the sarcomatous component forms a protruding tumor mass because it has abundant stroma positive for type IV collagen and laminin.

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The purpose of this study is to clarify the morphological characteristics and functional significance of the perisinusoidal stromal cells in hepatocellular carcinoma. The liver specimens surgically resected from 24 patients with hepatocellular carcinoma were studied by electron microscopy and immunohistochemistry using monoclonal antibodies against alpha-smooth muscle actin, vimentin and desmin. In the tissue space between endothelial cells and trabeculae of cancer cells, the stromal cells were frequently found. They were strongly positive for alpha-smooth muscle actin, weakly and less frequently positive for vimentin but negative for desmin. They varied in shape, size and distribution, stretching cytoplasmic processes and occasionally surrounding the trabeculae of cancer cells. They contained considerable amounts of microfilaments that were positive for alpha-smooth muscle actin and condensed in cell periphery. Along the cell membrane, the short dense areas and pinocytotic vesicles were seen. The external lamina incompletely invested the stromal cells. They were always surrounded by amorphous material. In the granulation tissue and fibrotic areas around necrotic cancer tissue, they were increased in size and number. On the other hand, immunohistochemically and ultrastructurally, they closely resembled the Ito cells in the piecemeal necrosis that showed myofibroblastic transformation. These results suggest that the perisinusoidal stromal cells in nonnecrotic cancer tissue produce the extracellular matrix in the tissue space and maintain the cancerous trabecular structure. After necrosis of cancer tissue, they may become activated and actively participate in the fibrosis.