Combined hepatocellular-cholangiocarcinoma: what the radiologist needs to know about biphenotypic liver carcinoma

Abstract

Combined hepatocellular-cholangiocarcinoma (CHC), also referred to as primary liver carcinoma (PLC) with biphenotypic differentiation, is an increasingly recognized subtype of malignant PLC encompassing varying morphologic forms thought to arise either from progenitor cell lineage or dedifferentiation of mature liver cells. Tumor cells express both biliary and hepatocellular markers by immunohistochemistry, and may also express progenitor cell and stem cell markers. Due to the relative rarity of this tumor type, little is known about the risk factors, imaging appearance, or prognosis. Few studies have demonstrated risk factors that overlap with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), though not all appear to arise in the background of cirrhosis. The imaging appearances of these tumors may overlap with those of HCC and CC and discriminating features such as classic enhancement patterns and biliary ductal dilation are not universally present. Serum tumor markers, such as alpha-fetoprotein and carbohydrate antigen 19-9, may be helpful when they are discordant with imaging or if both are elevated to a significant degree. In regards to management and prognosis, most studies demonstrate worse outcomes compared with HCC or CC. In the United States, the diagnosis of HCC is frequently made with imaging alone, and subsequent management decisions, including organ allocation for transplantation, rely upon the radiological diagnosis. Given the importance of radiological diagnosis, awareness of this tumor type is essential for appropriate management.