Answer: Mixed hepatocellular cholangiocarcinoma

Histology: This tumor arises in a background of a non-cirrhotic liver. The tumor has basically two morphologies which merge with each other. In some areas, the tumor is composed of polygonal eosinophilic cells with a trabecular or sinusoidal growth pattern, typical of hepatocellular carcinoma. Additionally, however, there are areas of small gland formations by cuboidal cells with some stromal inflammation and desmoplasia, suggestive of cholangiocarcinoma. Immunohistochemical stains confirm the mixed differentiation of this tumor. Foci of the tumor demonstrate granular cytoplasmic labeling for HepPar1 (not shown), while other areas demonstrate intracytoplasmic mucin and diffuse staining for cytokeratin 7 (figure 4) and Mucicarmine (figure 5).

Discussion: Pure hepatocellular carcinoma should not show overt gland formations, expression of biliary type cytokeratins such as cytokeratin 7, or intracytoplasmic mucin.Peripheral cholangiocarcinoma would lack the areas of true hepatocellular differentiation, as evidenced by the trabecular morphology and immunostaining for HepPar1.Metastatic adenocarcinoma is eliminated by the
presence of hepatocellular differentiation and clinical history.

The prognosis for mixed hepatocellular cholangiocarcinoma is similar to that of hepatocellular carcinoma and cholangiocarcinoma; namely, a poor one.Interestingly, these tumors typically are not associated with cirrhosis or a history of Hepatitis B, indicating that their demographics are
closer to that of cholangiocarcinoma than hepatocellular carcinoma.These tumors likely arise from a common stem cell that differentiates along hepatocellular and biliary lines.

Reference(s):
– Am J Surg Pathol 2002; 26: 989-997.
– Cancer 2002;94: 2040-2046.