Hepatocarcinogenesis in human liver

Due to the development of the imaging techniques and liver surgery, pathologists are encountered more frequently with preneoplastic liver lesions. Well-defined stages of human hepatocarcinogenesis have been distinguished recently. Dysplastic foci represent the earliest stage of this process. Small-cell dysplastic foci are tumor precursors, but the large-cell form of this lesion does not progress further. The next stage is the dysplastic nodule, this larger lesion can be recognized by imaging techniques and gross examination of the specimen. Low- and high-risk forms are distinguished based on the level of cytological and structural atypia. The small hepatocellular carcinomas have a diameter of less than 2 cm by definition. The small HCC of indistinctly nodular type is equivalent of in situ carcinomas in other organs and designated sometimes as early HCC. The small HCC of the distinctly nodular type can be interpreted as advanced cancer despite its small size. The distinction between these lesions can be facilitated by ancillary techniques. The so-called capillarization of the liver sinusoids during the progression is characterized by the increased expression of endothelial markers as CD31 and CD34. Immunostaining for CD44, beta-catenin and p53 has prognostic value. Molecular biological techniques reveal gradual epigenetic and DNA changes during the process of hepatocarcinogenesis. Global gene expression profiling of hepatocellular carcinomas may result in a new classification of this tumor and can reveal new potential therapeutic targets.