Thorium dioxide-related angiosarcoma of the liver. Pathomorphologic study of 29 autopsy cases

We describe the pathomorphologic features of 29 autopsy cases of thorium dioxide-related angiosarcoma (AGS) of the liver. The average (+/- SD) latent period after thorium dioxide injection was 36.2 +/- 5.2 years. Macroscopically, thorium dioxide-related AGS was divided into four types as follows: diffuse micronodular, multinodular, massive, and mixed multinodular and massive. Diffuse-micronodular and multinodular types were the most common. Histologically, thorium dioxide-related hepatic AGS was characterized by two cell types (spindle-shaped cells and polyhedral cells) and two structural patterns (sinusoidal and solid). There was no case composed of a solid pattern only. Immunohistochemically, factor VIII-related antigen was found to be positive in the endothelial cells of normal blood vessels and in the hyperplastic endothelial cells of the sinusoids, but negative in the tumor cells. Extramedullary hematopoiesis was found in both the tumorous and nontumorous areas in four cases. Erythrophagocytosis by the tumor cells was found in three cases. In the nontumorous area, varying degrees of sinusoidal dilatation with frequent hyperplastic changes of the sinusoidal lining cells were observed in all cases. These sinusoidal changes were frequently contiguous to AGS foci and were considered as a precursor change. In addition to the dominant sinusoidal changes, nodular hepatocytic hyperplasia was observed in two cases.