Histological heterogeneity in primary and metastatic classic combined hepatocellular-cholangiocarcinoma: a case series

Virchows Arch. 2017 Nov;471(5):619-629. doi: 10.1007/s00428-017-2196-x. Epub 2017 Jul 13.


Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare and aggressive primary liver cancer with both hepatocellular and cholangiocellular differentiation. Due to its bi-phenotypic component, cHCC-CC is a heterogeneous tumour and histopathological analysis of metastatic deposits is poorly characterized. In this retrospective study, we describe four patients in whom the histology from resected specimens of both primary and recurrent and/or metastatic tumour was available for comparison and immunohistochemical characterization. Our study shows that recurrent or metastatic deposits replicate the heterogeneity of the primary cHCC-CC, that even originally small foci of divergent differentiation can become predominant later on and that hepatocellular and cholangiocellular components can show different tropism in distant organs. In our experience, the behaviour of recurrent/metastatic cHCC-CC is unpredictable and histological examination is necessary to guide treatment options at present.

Keywords: Combined hepatocellular-cholangiocarcinoma; Heterogeneity; Metastasis.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aged
  • Bile Duct Neoplasms / pathology*
  • Bile Ducts, Intrahepatic / pathology
  • Carcinoma, Hepatocellular / pathology*
  • Cholangiocarcinoma / pathology*
  • Female
  • Humans
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Metastasis / pathology
  • Neoplasm Recurrence, Local / pathology
  • Retrospective Studies