Mixed Hepatocellular/Cholangiocarcinomas: Current Perspectives and Management
Mixed hepatocellular-cholangiocarcinoma (cHCC-CC) accounts for 0.4–14% of primary liver tumours. The diagnosis is based on histology using a combination of morphology, immunohistochemistry, in situ hybridisation and molecular biology to determine lineage. The WHO (2010) classification demonstrates the complexity of the spectrum of tumours. It defines two groups, classical cHCC-CC and cHCC-CC, with stem cell features; the latter is subdivided. Genetic studies are limited with findings similar to those observed in both classical HCC and intrahepatic cholangiocarcinoma. A recent observation is the presence of IDH1/IDH2 mutations in tumours histologically resembling HCC but with clinical and genetic features of cholangiocarcinoma.
The rarity of this tumour has made it difficult to define epidemiologically. Risk factors are similar to those for other primary liver tumours. cHCC-CC is an aggressive tumour with poor long-term outcomes. It develops asymptomatically until the disease is advanced. Radiologically, the majority resemble classical HCC. However, a recent study has suggested subtle differences may be detectable in some tumours. In addition, cHCC-CC may secrete both AFP and CA19-9. However, the diagnosis is dependent on histological assessment of a whole tumour, and sampling error is a concern when examining needle biopsies.
The optimal management is hepatic resection with hilar lymph node dissection. Nodal involvement resembles that of cholangiocarcinoma. Five-year survival rates following resection are around 28%. The role of liver transplantation is debated with outcomes available for only small patient numbers. For those not amenable to surgery, recent data has indicated activity associated with locoregional treatments and systemic anticancer therapy.
KeywordsMixed hepatocellular-cholangiocarcinoma IDH1/IDH2 mutation Histological diagnosis Hepatic resection Locoreional therapy Systemic therapy
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