Thorotrast-induced hepatic angiosarcoma, and combined hepatocellular and cholangiocarcinoma in a single patient

Abstract

A 64-year-old man developed hepatic angiosarcoma, and combined hepatocellular and cholangiocarcinoma, 36 years after Thorotrast administration. The patient presented with a large mass in the right upper quadrant. His serum a-fetoprotein increased from 800 ng/ml to 51.2 &ml, and liver biopsy disclosed hepatocellular carcinoma. At autopsy, the liver had two different malignant neoplasms; angiosarcoma and combined hepatocellular and cholangiocarcinoma. Metastases of angiosarcoma to both lungs and of cholangiocarcinoma to periaortic lymph nodes were also seen. Interestingly, some neoplastic cells of angiosarcoma exhibited globular hyaline inclusions, which were Periodic-Acid-Schiff reaction positive and diastase-resistant.Cancer 49:2161-2164, 1982.HOROTRAST (Th), a 25% colloidal solution of tho-T rium dioxide, had been utilized all over the world in the 1930s and 1940s as a contrast medium for various radiographic applications. Thorium has a radioactive half life of 1.39 X 10" years and a biological half life of 400 years, and its energy consists of 90% alpha, 9% beta, and 1% gamma radiation. Although warnings of possible late effects of Th had been given even at its introduction, Th was widely used because it lacked acute toxicity and it gave excellent radiographical results. In 1947, MacMahon et al.' first reported the occurrence of an angiosarcoma (AGS) as a late effect of Th administration. A variety of Th-induced malignant neoplasms have been reported subsequently. It is our purpose to describe an unusual autopsy case of simultaneous hepatic AGS and combined hepatocellular and cholangiocarcinoma occurring in a patient 36 years after Th administration. Case ReportA 64-year-old man was admitted to a local hospital in early November, 1978, with persistent cough and right upper quadrant pain of three weeks' duration. The medical history included left femoral arteriography, utilizing Th as a contrast medium, for a sensory disturbance of the left leg in 1943. On From The First Department of Pathology, Kurume University School of Medicine: *Lecturer. TFellow, $Associate Professor, §Pro-fessor, "The Kurume National Hospital.The authors wish to thank Drs. Hans Popper and Stephen J. Galli for reviewing the slides and the manuscript.Address for reprints: Masamichi Kojiro, MD,

Combined hepatocellular‐cholangiocarcinoma with angiosarcomatoid change: A case report with immunohistochemical study

“…Second, a small portion of undifferentiated spindle cells expressed pan‐cytokeratin, suggesting that the sarcomatoid lesion was derived from HCC. Simultaneous occurrence of angiosarcoma and cHCC‐CCA has been previously reported in a single patient treated with Thorotrast . In that case, carcinoma lesions and angiosarcoma lesions were distributed separately, with overlap in several areas.…”

“…cHCC-CCA has been previously reported in a single patient treated with Thorotrast. 12 In that case, carcinoma lesions and angiosarcoma lesions were distributed separately, with overlap in several areas. As the present case involved a grossly well-defined single nodule containing both carcinomatous and sarcomatous lesions, we concluded that it was a multi-differentiated single tumor rather than a collision tumor.…”

Combined Hepatocellular-Cholangiocarcinoma

“…CHCC-C was found in combination with other liver tumors, e.g., hepatic angiosarcoma in a patient with thorotrastosis (Kojiro et al 1982).…”

Possible Mechanism for the Formation of Tumors by Thorotrast Based on Crystallographic Characterization of Thorotrast Particles in Tissues

“…This substance was injected intravenously into humans as a radiological enhancement medium in angiography from 1927 to 1954 in Japan [2]. Following the injection, many patients have developed malignant tumors presumably due to the deposition of Thorotrast in the reticulo-endothelial system [3][4][5][6][7]. We had previously reproted that Thorotrast was deposited in human tissues mainly in the form of Th02 [8].…”