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Cholangiocarcinoma: Classification, Histopathology and Molecular Carcinogenesis

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  • Published:
Pathology & Oncology Research

Abstract

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.

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Funding

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.

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  1. Gábor Lendvai and Tímea Szekerczés equally contributed

Authors and Affiliations

  1. 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, H-1091, Hungary

    Gábor Lendvai, Tímea Szekerczés, Idikó Illyés, Réka Dóra, Endre Kontsek, Alíz Gógl, András Kiss, Zsuzsa Schaff & Katalin Borka

  2. 2nd Department of Internal Medicine, Semmelweis University, Budapest, 1085, Hungary

    Klára Werling

  3. 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, 1085, Hungary

    Ilona Kovalszky

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  1. Gábor Lendvai
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Correspondence to Zsuzsa Schaff.

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Lendvai, G., Szekerczés, T., Illyés, I. et al. Cholangiocarcinoma: Classification, Histopathology and Molecular Carcinogenesis. Pathol. Oncol. Res. 26, 3–15 (2020). https://doi.org/10.1007/s12253-018-0491-8

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