Development of hepatic angiosarcoma in man induced by vinyl chloride, thorotrast, and arsenic. Comparison with cases of unknown etiology.
Studies on the induction of hepatic angiosarcoma in man by vinyl- chloride (75014), thorium-dioxide (1314201) (Thorotrast), and inorganic arsenic (7440382) were summarized. Epidemiological and histological data on biopsies from 167 cases of hepatic angiosarcoma, 128 males including four children, were examined. Nineteen cases were known to have exposure to vinyl-chloride, 28 to Thorotrast, and five to Fowler's solution (a medicinal arsenical). The etiology of the other cases was unknown. The same general patterns of development were seen in all cases, independent of the etiology. The most prominent feature of Thorotrast associated lesions was deposition of large amounts of Thorotrast in dense connective tissue in the capsule, portal tracts, and parenchyma. Proliferation of bile ductules was absent or rarely seen, in contrast to the cases resulting from vinyl-chloride and arsenical exposure. Development of hepatic angiosarcoma was characterized by a precursor stage in which hepatocytic proliferation occurred in association with varying degrees of sinusoidal lining cell proliferation and sinusoidal dilatation. In the transition to angiosarcoma, five processes were involved in varying degrees: proliferation with increasing anaplasia of intralobular endothelial cells, initial hyperplasia of hepatocytes followed by atrophy and disappearance, increasing fibrosis in perisinusoidal spaces, progression of sinusoidal dilatation to peliosis, and sarcomatous transformation of lining cells of sinusoids and portal capillaries. The authors suggest that the uniform evolution indicates that an environmental factor is involved in the cases of unknown etiology.