RESUMO
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.
Assuntos
Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Neoplasias dos Ductos Biliares/classificação , Neoplasias dos Ductos Biliares/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinogênese/genética , Carcinogênese/metabolismo , Colangiocarcinoma/classificação , Colangiocarcinoma/genética , Humanos , Neoplasias Hepáticas/classificação , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Mutação , Estadiamento de Neoplasias , Lesões Pré-Cancerosas/patologia , Prognóstico , Microambiente TumoralRESUMO
The hepatitis C virus is an RNA virus, which belongs to the genus Hepaciviruses of the family Flaviviridae. Chronic hepatitis, cirrhosis, and ultimately even liver cancer may develop in over 80% of infected cases. The histological features of hepatitis C and hepatitis caused by other hepatotropic viruses show many similarities, however, certain specific histological characteristics are observable. Accordingly, intense lymphocytic infiltration around the periportal areas, steatosis and biliary alterations are frequent findings. Further characteristics of hepatitis C include liver cell destruction (apoptosis, necrosis), periportal inflammation and fibrosis, the degrees of which can be determined by means of the histology activity index. Our knowledge on the hepatitis C virus genome and the mechanism of replication of the virus have established the use of modern, direct-acting antivirals in the treatment of chronic hepatitis C.
