Advertisement

Liver Cancers pp 169-178 | Cite as

Mixed Hepatocellular/Cholangiocarcinomas: Current Perspectives and Management

  • Ray Tan
  • Alberto Quaglia
  • Paul J. RossEmail author
Chapter

Abstract

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.

Keywords

Mixed hepatocellular-cholangiocarcinoma IDH1/IDH2 mutation Histological diagnosis Hepatic resection Locoreional therapy Systemic therapy 

References

  1. 1.
    Wells HG. Primary carcinoma of the liver. Am J M Sc. 1903;126:403–17.CrossRefGoogle Scholar
  2. 2.
    RA A, Lisa JR. Combined liver cell and bile duct carcinoma. Am J Surg Pathol. 1949;25:647–55.Google Scholar
  3. 3.
    Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer. 1954;7(3):462–503.CrossRefGoogle Scholar
  4. 4.
    Akiba J, Nakashima O, Hattori S, Tanikawa K, Takenaka M, Nakayama M, Kondo R, Nomura Y, Koura K, Ueda K, Sanada S, Naito Y, Yamaguchi R, Yano H. Clinicopathologic analysis of combined hepatocellular-cholangiocarcinoma according to the latest WHO classification. Am J Surg Pathol. 2013;37(4):496–505.  https://doi.org/10.1097/PAS.0b013e31827332b0.CrossRefPubMedGoogle Scholar
  5. 5.
    Brunt EM, Paradis V, Sempoux C, Thiese ND. Biphenotypic (hepatobiliary) primary liver carcinomas: the work in progress. Hepatic Oncol. 2015;2(3):255–73.CrossRefGoogle Scholar
  6. 6.
    Zen C, Zen Y, Mitry RR, Corbeil D, Karbanová J, O’Grady J, Karani J, Kane P, Heaton N, Portmann BC, Quaglia A. Mixed phenotype hepatocellular carcinoma after transarterial chemoembolization and liver transplantation. Liver Transpl. 2011;17(8):943–54.  https://doi.org/10.1002/lt.22314.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Nishihara Y, Aishima S, Kuroda Y, Iguchi T, Taguchi K, Asayama Y, Taketomi A, Kinukawa N, Honda H, Tsuneyoshi M. Biliary phenotype of hepatocellular carcinoma after preoperative transcatheter arterial chemoembolization. J Gastroenterol Hepatol. 2008;23(12):1860–8.  https://doi.org/10.1111/j.1440-1746.2008.05601.x.CrossRefPubMedGoogle Scholar
  8. 8.
    Lee JS, Heo J, Libbrecht L, Chu IS, Kaposi-Novak P, Calvisi DF, Mikaelyan A, Roberts LR, Demetris AJ, Sun Z, Nevens F, Roskams T, Thorgeirsson SS. A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat Med. 2006;12(4):410–6.CrossRefGoogle Scholar
  9. 9.
    Marquardt JU, Andersen JB, Thorgeirsson SS. Functional and genetic deconstruction of the cellular origin in liver cancer. Nat Rev Cancer. 2015;15(11):653–67.  https://doi.org/10.1038/nrc4017.CrossRefPubMedGoogle Scholar
  10. 10.
    Cancer Genome Atlas Research Network. Comprehensive and integrative genomic characterization of hepatocellular carcinoma. Cell. 2017;169(7):1327–1341.e23.  https://doi.org/10.1016/j.cell.2017.05.046.CrossRefGoogle Scholar
  11. 11.
    Garancini M, Goffredo P, Pagni F, Romano F, Roman S, Sosa JA, Giardini V. Combined hepatocellular-cholangiocarcinoma: a population-level analysis of an uncommon primary liver tumor. Liver Transpl. 2014;20(8):952–9.  https://doi.org/10.1002/lt.23897.CrossRefPubMedGoogle Scholar
  12. 12.
    Vilchez V, Shah MB, Daily MF, Pena L, Tzeng CW, Davenport D, Hosein PJ, Gedaly R, Maynard E. Long-term outcome of patients undergoing liver transplantation for mixed hepatocellular carcinoma and cholangiocarcinoma: an analysis of the UNOS database. HPB (Oxford). 2016;18(1):29–34.  https://doi.org/10.1016/j.hpb.2015.10.001.CrossRefGoogle Scholar
  13. 13.
    Potretzke TA, Tan BR, Doyle MB, Brunt EM, Heiken JP, Fowler KJ. Imaging features of biphenotypic primary liver carcinoma (Hepatocholangiocarcinoma) and the potential to mimic hepatocellular carcinoma: LI-RADS analysis of CT and MRI features in 61 cases. AJR Am J Roentgenol. 2016;207(1):25–31.  https://doi.org/10.2214/AJR.15.14997.CrossRefPubMedGoogle Scholar
  14. 14.
    The Liver Cancer Study Group of Japan. Primary liver cancer in Japan: clinicopathologic features and results of surgical treatment. Ann Surg. 1990;211:277–87.Google Scholar
  15. 15.
    Groeschl RT, Turaga KK, Clark Gamblin T. Transplantation versus resection for patients with combined hepatocellular carcinoma-cholangiocarcinoma. J Surg Oncol. 2013;107(6):608–12.  https://doi.org/10.1002/jso.23289.CrossRefPubMedGoogle Scholar
  16. 16.
    De Vito C, Sarker D, Ross P, Heaton N, Quaglia A. Histological heterogeneity in primary and metastatic classic combined hepatocellular-cholangiocarcinoma: a case series. Virchows Arch. 2017;  https://doi.org/10.1007/s00428-017-2196-x.CrossRefGoogle Scholar
  17. 17.
    Fowler K, Saad NE, Brunt E, Doyle MB, Amin M, Vachharajani N, Tan B, Chapman WC. Biphenotypic primary liver carcinomas: assessing outcomes of hepatic directed therapy. Ann Surg Oncol. 2015;22(13):4130–7.  https://doi.org/10.1245/s10434-015-4774-y.CrossRefPubMedGoogle Scholar
  18. 18.
    Rogers JE, Bolonesi RM, Rashid A, Elsayes KM, Elbanan MG, Law L, Kaseb A, Shroff RT. Systemic therapy for unresectable, mixed hepatocellular-cholangiocarcinoma: treatment of a rare malignancy. J Gastrointest Oncol. 2017;8(2):347–51.  https://doi.org/10.21037/jgo.2017.03.03.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Govaere O, Roskams T. Pathogenesis and prognosis of hepatocellular carcinoma at the cellular and molecular levels. Clin Liver Dis. 2015;19(2):261–76.  https://doi.org/10.1016/j.cld.2015.01.002.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Medical Oncology, Guy’s CancerGuy’s and St Thomas’ NHS Foundation TrustLondonUK
  2. 2.The Institute of Liver StudiesKing’s College HospitalLondonUK
  3. 3.Department of OncologyKing’s College Hospital NHS Foundation TrustLondonUK

Personalised recommendations