Oral contraceptive‐associated liver cell adenoma and hepatocellular carcinoma. Cytomorphology and mechanism of malignant transformation

From January 1976 to May 1990, 1673 patients with a liver mass or masses detected by imaging techniques underwent percutaneous fine‐needle aspiration biopsy of the liver. Of these, 99 were diagnosed cytologically as “hepatocellular carcinoma” and 9 as “consistent with liver cell adenoma.” The cytologic diagnoses were confirmed in the follow‐up of all cases. Among the 99 patients with hepatocellular carcinoma, 3 had taken oral contraceptives for a period of 10, 11, and 12 years, respectively. The nine patients with liver cell adenoma were all users of oral contraceptives over a period ranging from 5 to 10 years. Of these, two who had taken oral contraceptives for a period of 8 and 10 years, respectively, had foci or areas of liver cell dysplasia within the adenomas. The cytologic criteria for the diagnosis of liver cell dysplasia included cytoplasmic and nuclear enlargement, nuclear pleomorphism together with prominent nucleoli, hyperchromasia and multinucleation. The cytologic features of liver cell dysplasia strikingly mimic hepatocellular carcinoma. From this study, the foci or areas of liver cell dysplasia arising within the liver cell adenomas appear to be the missing link responsible for the transformation of liver cell adenoma to carcinoma. It is believed that liver cell adenomas are not premalignant and may undergo reversible change after withdrawal of causative agents, whereas liver cell dysplasia is an irreversible, premalignant change and will eventually progress to hepatocellular carcinoma.