Angiosarcoma of the Liver and Other Hepatic Malignancies in the Russian Cohort of Mayak Nuclear Workers.

Human occupational exposure to ionizing radiation has been linked to increased risks of developing cancers, including solid tumors. In particular, 239Pu, used in the production of nuclear weapons, has been associated with a higher risk of malignancies of the lungs, liver, and bones, but the specific patterns of malignant histology have not been well described in humans. We assessed the pathological characteristics of liver cancers that occurred in a Russian cohort of nuclear workers from the Mayak Production Association, with a special emphasis on angiosarcoma, and studied the relationships between dosimetry, sex, and histology. The subjects included two main groups of workers whose biological specimens were collected during autopsies: thirty-one were diagnosed with liver cancers (cases), and 38 workers were cancer-free (controls). An independent pathologist reviewed all liver tissues from these cancer cases and performed immunohistochemistry to confirm the diagnoses (angiosarcoma, hepatocellular carcinoma, or cholangiocarcinoma). A third group consisted of 36 workers who developed liver cancer but for whom no biological samples were available. Radiation dose levels, along with sex and age distributions, were compared statistically among the three types of liver tumors and the control groups. There was a predominance of females (9 of 13, 69%) among the workers who developed angiosarcoma of the liver, whereas a male predominance characterized both hepatocellular carcinoma (9 of 9, 100%) and cholangiocarcinoma (8 of 9, 89%). A male predominance was also observed in the group of workers with liver cancer but without biological samples (22 of 36, 61%) and in the group of workers without liver cancer (30 of 38, 79%). Occupational differences were evident, with angiosarcoma patients who had biological samples representing the largest proportion (9 of 13) of plutonium metallurgical plant workers (the most highly exposed occupation to plutonium in the cohort), while the remainder (4 of 13) occurred among the radiochemical plant workers. Compared to other groups, those workers with biological samples who developed angiosarcoma had the largest accumulated and widest range of external doses absorbed by the liver, as well as the highest absorbed doses of 239Pu to the liver. Females with biological samples who developed liver cancer also had some of the highest accumulated doses from 239Pu, exceeding 1 Gy in some instances. Our observations of histology, sex, occupation, and dose patterns provide possible clues to the unusual pattern of liver malignancies, particularly angiosarcoma, related to aspects of plutonium exposure.