Synchronous hepatocellular carcinoma and cholangiocarcinoma arising in two different dysplastic nodules

We present the first reported case of explant cirrhotic liver that had synchronous cholangiocarcinoma and hepatocellular carcinoma arising in two different high-grade dysplastic nodules. The patient was a 55-year-old woman who had hepatitis B virus-associated liver cirrhosis for 3 years. The moderately differentiated cholangiocarcinoma occurred in high-grade dysplastic nodule with a 1.7-fold cell density compared with that of cirrhotic nodule. The hepatocellular carcinoma arose in a nodule-in-nodule pattern within a peripherally low-grade and centrally high-grade dysplastic nodule and had a 2.7-fold cell density compared with that of cirrhotic nodule. By immunohistochemistry, the tumor cells of the cholangiocarcinoma as well as bile ductular cells in dysplastic nodule were diffusely positive for cytokeratin 7, whereas hepatocellular carcinoma cells and dysplastic hepatocytes were negative for cytokeratin 7. The c-kit-positive hepatic progenitor cells were singly scattered between hepatocytes, and their number was highest in cirrhotic nodule and decreased in dysplastic nodule, whereas they were absent in cholangiocarcinoma and hepatocellular carcinoma arising in dysplastic nodules. Proliferation indices were progressively increased in cirrhotic nodule, dysplastic nodule, and cholangiocarcinoma or hepatocellular carcinoma, sequentially. These observations indicate that cholangiocarcinoma as well as hepatocellular carcinoma can develop in dysplastic nodule and that hepatic progenitor cells might play a role in the early stage of cholangiocarcinogenesis and hepatocarcinogenesis.