Hepatocellular carcinoma with an unusual neuroendocrine component

We report a rare case of hepatocellular carcinoma (HCC) with an unusual neuroendocrine component. During a follow-up study for chronic hepatitis C in a 71-year-old man, a nodular lesion showed rapid growth from 1 cm to 4 cm in diameter within 3 months. Histologically, the tumor was consistent with moderately differentiated HCC, but was intermingled with nests of small round cells with scarce cytoplasm, which resembled those found in small cell carcinoma. This population formed small solid nests among the trabecular structures. Immunohistochemically the small round cell component of the tumor was strongly positive for neuron-specific enolase (NSE), chromogranin A and synaptophysin, but hepatocyte paraffin-1 (HP-1) and alpha-fetoprotein (AFP) were negative. In contast, HP-1 and AFP were positive, and NSE, chromogranin A and synaptophysin were negative in moderately differentiated HCC tissues. Electron microscopy revealed many intracytoplasmic neurosecretory granules in the small round cells. The labeling indexes of p53 and Ki-67 were significantly higher in the small round cell component than in the moderately differentiated HCC component. Overall, we conclude that this nodule was HCC with neuroendocrine differentiation.