Cholangiocarcinoma: Classification, Histopathology and Molecular Carcinogenesis

  • Gábor Lendvai
  • Tímea Szekerczés
  • Idikó Illyés
  • Réka Dóra
  • Endre Kontsek
  • Alíz Gógl
  • András Kiss
  • Klára Werling
  • Ilona Kovalszky
  • Zsuzsa SchaffEmail author
  • Katalin Borka


Cholangiocarcinoma (CC) is the second most common tumor of the liver, originating from the biliary system with increasing incidence and mortality worldwide. Several new classifications review the significance of tumor localization, site of origin, proliferation and biomarkers in the intrahepatic, perihilar and distal forms of the lesion. Based on growth pattern mass-forming, periductal-infiltrating, intraductal, undefined and mixed types are differentiated. There are further subclassifications which are applied for the histological features, in particular for intrahepatic CC. Recognition of the precursors and early lesions of CC including biliary intraepithelial neoplasia (BilIN), intraductal papillary neoplasm of the bile ducts (IPNB), biliary mucinous cystic neoplasm (MCNB) and the candidate precursors, such as bile duct adenoma and von Meyenburg complex is of increasing significance. In addition to the previously used biliary markers detected by immunohistochemistry, several new markers have been added to the differentiation of both the benign and malignant lesions, which can be used to aid in the subclassification in association with the outcome of CC. Major aspects of biliary carcinogenesis have been revealed, yet, the exact way of this diverse process is still unclear. The factors contributing to molecular cholangiocarcinogenesis include various risk factors, different anatomical localizations, multiple cellular origins, genetic and epigenetic alterations, tumor microenvironment, heterogeneity and clonal evolution. Driver mutations have been identified, implying that they are optimal candidates for targeted therapy. The most promising therapeutic candidates have entered clinical trials.


Cholangiocarcinoma Liver cancer Biliary markers Stem cells MicroRNA 



This work was supported by grant #OTKA 108548 by the Hungarian National Research Foundation and grant #NVKP_16_1–2016-0004 by the Hungarian National Research, Development and Innovation Office.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest with respect to the research, authorship, and/or publication of this article.

Supplementary material

12253_2018_491_MOESM1_ESM.docx (150 kb)
ESM 1 (DOCX 150 kb)


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Copyright information

© Arányi Lajos Foundation 2018

Authors and Affiliations

  • Gábor Lendvai
    • 1
  • Tímea Szekerczés
    • 1
  • Idikó Illyés
    • 1
  • Réka Dóra
    • 1
  • Endre Kontsek
    • 1
  • Alíz Gógl
    • 1
  • András Kiss
    • 1
  • Klára Werling
    • 2
  • Ilona Kovalszky
    • 3
  • Zsuzsa Schaff
    • 1
    Email author
  • Katalin Borka
    • 1
  1. 1.2nd Department of PathologySemmelweis UniversityBudapestHungary
  2. 2.2nd Department of Internal MedicineSemmelweis UniversityBudapestHungary
  3. 3.1st Department of Pathology and Experimental Cancer ResearchSemmelweis UniversityBudapestHungary

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