Answer: Intrahepatic cholangiocarcinoma

Histology: This is a lesion, which, while grossly circumscribed, does infiltrate at its borders between hepatocytes. The lesion is centrally sclerotic and hyalinized. Much of the tumor has a trabecular growth pattern which simulates that of hepatocellular carcinoma. Mitoses and focal necrosis are readily evident. There are areas of tubule formation. The lesion is immunoreactive for cytokeratin 7 and not for HepPar-1.

Discussion: Hepatocellular carcinoma would label for HepPar- 1, and typically does not label for cytokeratin 7 or cytokeratin 20. Hepatocellular carcinomas typically do not have the centrally hyalinized areas of an intrahepatic, peripheral cholangiocarcinoma, unless they belong to the sclerosing or fibrolamellar variants. Bile duct adenomas are typically small lesions which are subcapsular in location. While these lesions may show modest nuclear atypia, they typically do not show mitotic activity or necrosis. An epithelioid hemangioendothelioma would show similar central hyalinization, though this typically has a more myxoid appearance. These tumor cells may label for cytokeratin, but they have a more “blistered” cytologic appearance, and will label for endothelial markers such as CD34 and CD31.

Intrahepatic cholangiocarcinoma is approximately ten fold as common in Japan as it is in the United States. Risk factors for this include fibrocystic diseases of the liver such as Caroli’s disease and solitary cysts, recurrent pyogenic cholangitis and intrahepatic lithiasis, and parasitic disorders such as Clonorchis sinensis. These lesions may be classified as either peripheral (mass forming type) such as the current case, or periductal infiltrating type based upon their growth pattern. By immunohistochemistry, these tumors label for cytokeratin 7, and approximately 50 percent will label for cytokeratin 20. CEA is usually positive, while HepPar-1 and CD10 are negative.