Primary liver carcinoma of intermediate (hepatocyte-cholangiocyte) phenotype

Background/Aims: Recent evidence of hepatic progenitor cells with the bipotential to differentiate into hepatocytes and cholangiocytes gives rise to the suggestion that primary hepatic carcinomas with features intermediate between hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) may originate from hepatic progenitor cells. Methods: Fifty-four cases of primary liver carcinomas were selected and an immunohistochemical analysis was performed using hepatocytic markers (α-fetoprotein, hepatocyte), cholangiocytic markers (carcinoembryonic antigen, cytokeratin 19) and progenitor cell marker (c-kit). Results: Thirteen cases designated 'intermediate' carcinomas demonstrated strands/trabeculae of small, uniform, round-to-oval cells with scanty cytoplasm and hyperchromatic nuclei embedded within a thick desmoplastic stroma. Six were designated transitional type combined hepatocellular-cholangiocarcinoma (CHC). Ten were named HCC small cell type, demonstrating similar features to typical HCC, but composed of smaller cells. Simultaneous expression of hepatocytic and cholangiocytic markers was demonstrated in 8/13 (61.5%), 4/6 (66.7%), and 3/10 (30%) cases of intermediate carcinomas, transitional CHCs, and HCC small cell type, respectively, and c-kit expression was noted in 10/13 (76.9%), 4/6 (66.7%) and 7/10 (70%) cases, in the same order. Conclusions: Intermediate carcinoma may be a distinct type of primary liver carcinoma, morphologically and phenotypically intermediate between HCC and CC, which originates from transformed hepatic progenitor cells.