Primary liver cancer with bidirectional differentiation into hepatocytes and biliary epithelium

A 70-year old Japanese man with hepatitis B infection developed a 4.8-cm liver tumor in the right lobe. Computed tomographic findings suggested hepatocellular carcinoma or combined hepatocellular and cholangiocarcinoma. After right hepatectomy, the cut surface of the resected specimen showed a whitish tumor with indistinct borders. Microscopically, the tumor consisted of pleomorphic, eosinophilic cells forming thickened trabeculae, suggesting hepatocellular carcinoma, and also tumor cells forming glandular structures, suggesting adenocarcinoma. Cells comprising both the trabeculae and the glands were immunoreactive for cytokeratin (CK) 19. In some gland-forming cells, varying immunoreactivity for CK7 and carcinoembryonic antigen (CEA) was observed. In the cytoplasm of cells in the thickened trabeculae, hepatocyte paraffin (HepPar) 1 and alpha-fetoprotein (AFP) were focally reactive. Some of these tumor cells were also reactive for CK19. Accordingly, we concluded that this tumor was a combined hepatocellular and cholangiocarcinoma whose cells had undergone divergent differentiation into hepatocytes and biliary epithelium. Because the tumor expressed markers of both phenotypes, it may have originated from cells intermediate between hepatocytes and biliary epithelium. A few reported cases have shown similar histologic features.