[Hepatocellular carcinoma--from macroscopy to molecular pathology]

Hepatocellular carcinoma (HCC) is a tumor with rather bad prognosis. Recent years, however, have seen considerable progress in the diagnostics and treatment of this disease, contributing to better understanding of its molecular pathogenesis. Large regenerative nodules, low and high grade dysplastic nodules are premalignant alterations of HCC developing on the grounds of cirrhosis. Microscopically the WHO distinguishes trabecular, acinar (pseudoglandular), scirrhous and solid forms. Special histological subtypes are the clear cell, fibrolamellar and mixed hepato-cholangiocellular variants. The prognostic significance of these histological types is argued. The fibrolamellar, non-cirrhotic form of HCC occurring in young age is considered to be of better prognosis, but this is probably due to the fact that this type is not accompanied by cirrhosis. Certain tumor markers may help the diagnosis, such as alpha-fetoprotein (AFP), glypican-3, survivin, the recently described agrin and claudins, furthermore, the hepatocyte specific antigen (HSA), which confirms the hepatocytic origin of the tumor. Recently, the diagnostic significance of microRNAs, primarily of the hepatocyte-specific mir122 has also emerged. In addition to the Barcelona Clinic Liver Cancer (BCLC) staging classification which determines the course of therapy, the molecular classification of HCC is based on key molecular alterations, many of which are observable in all HCC cases, whereas some alterations are only detectable in certain tumors.