Hepatocellular carcinoma with biliary and neuroendocrine differentiation: A case report

BACKGROUND: Liver tumors with dual differentiations [combined hepatocellular carcinoma (HCC) and cholangiocarcinoma] are common. However, liver tumors that exhibit hepatocellular, biliary, and neuroendocrine differentiation are exceedingly rare, with only three previous case reports in the literature. CASE SUMMARY: A 65-year-old female with a previous history of hepatitis C and a distant history of low grade, well-differentiated rectal neuroendocrine tumor was found to have two liver lesions in segment 4 and segment 7 on imaging. Serum alpha-fetoprotein and chromogranin A were elevated. Biopsy of the larger lesion in segment 4 revealed a high-grade tumor, with morphologic and immunohistochemical features of a neuroendocrine tumor. Given the previous history of rectal neuroendocrine tumor, imaging investigation, serologic markers, and biopsy findings, metastatic neuroendocrine tumor was considered. Subsequent regional resection of these hepatic lesions revealed the segment 4 lesion to be a HCC with additional biliary and neuroendocrine differentiation and the segment 7 lesion to be a cholangiocarcinoma with neuroendocrine differentiation. Follow-up of the patient revealed disease recurrence in the dome of the liver and metastasis in retro-pancreatic lymph nodes. The patient eventually expired due to complications of chemotherapy. CONCLUSION: HCC cases with additional biliary and neuroendocrine differentiation are exceedingly rare, posing a diagnostic challenge for clinicians and pathologists.