Hepatocellular Carcinoma With a Grade 3 Neuroendocrine Tumor Component: A Case Report

Mixed hepatocellular carcinoma (HCC) and neuroendocrine tumor (NET) constitute an exceedingly rare and diagnostically challenging entity. We report a 70-year-old man with hepatitis C-related cirrhosis and multifocal HCCs, who was status post multiple microwave and radiofrequency ablation procedures. Total hepatectomy revealed a 1.9-cm viable tumor that, on histologic examination, showed moderately differentiated HCC with trabecular and pseudoacinar growth patterns and expression of albumin, arginase-1, and HepPar-1. Notably, a neuroendocrine component comprising ∼20% of the tumor volume was identified. This component consisted of sheets of intermediate-sized cells with inconspicuous nucleoli and scant cytoplasm. Scattered tumor cells with enlarged nuclei were present, but mitotic figures were difficult to identify, and no necrosis was observed. Immunohistochemically, these tumor cells were positive for synaptophysin and negative for hepatocellular markers, with wild-type p53, retained nuclear RB1, and patchy SSTR2A expression. The Ki-67 labeling index was heterogeneous, ranging from 5% in low-proliferation areas to 31% in hotspots, with an average of 11%. The morphologic and immunohistochemical findings supported a diagnosis of mixed HCC and grade 3 (high-grade) well-differentiated NET. This diagnosis should be distinguished from mixed HCC and neuroendocrine carcinoma given important differences in therapeutic decision-making and prognostic assessment.