Development of hepatic angiosarcoma in man induced by vinyl chloride, thorotrast, and arsenic. Comparison with cases of unknown etiology

Am J Pathol. 1978 Aug;92(2):349-76.


Examples of human angiosarcoma following exposure to vinyl chloride, Thorotrast, or arsenic (medicinal and industrial) and cases, including children, of unknown etiology were studied to establish diagnostic criteria and to study their evolution. The uniform evolution suggests an environmental factor also in the cases of unknown etiology, which may be established by epidemiologic studies. A precursor stage is charaterized by areas of combined hyperlasia of hepatocytes and a variety of sinusoidal and perisinusoidal cells associated with excess of reticulin and with sinusoidal dialation. The diagnostically useful picture in silver impregnations indicated reticulum formation by the perisinusoidal cells, presumably the libocytes. The hepatocytic proliferation suggests a hepatocarcinogenic but usually not fully expressed potential. The mixed hyperplasia of the various sinusoidal cells proceeds to an overgrowth of angiosarcoma cells, presumably derived from endothelial cells. In early stages they are usually in contact with hepatocytes (intralobular growth). A trabecular arrangement results from loosening of the lobular plate arrangement by dilatation of sinusoids, leading to primary peliosis. With disappearance of the hepatocytes, various growth patterns develop, terminating in nodular, solid angiosarcoma composed of either spindle-shaped or polyhedral cells which undergo necrosis or hemorrhage (secondary peliosis). The interaction between hepatocytes and sinusoidal cells requires elucidation.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Arsenic / adverse effects*
  • Child, Preschool
  • Female
  • Hemangiosarcoma / chemically induced*
  • Hemangiosarcoma / diagnosis
  • Hemangiosarcoma / pathology
  • Humans
  • Hyperplasia
  • Liver / pathology*
  • Liver Neoplasms / chemically induced*
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Thorium Dioxide / adverse effects*
  • Vinyl Chloride / adverse effects*
  • Vinyl Compounds / adverse effects*


  • Vinyl Compounds
  • Thorium Dioxide
  • Arsenic
  • Vinyl Chloride