Histopathological classification of hepatocellular carcinoma

Recent advances in the understanding of HCC heterogeneity have shown not only distinct molecular classes with potential therapeutical implications but also have suggested that subclasses might be mirrored by tumour morphology and phenotype. The classification of HCC is therefore shifting from a more traditional, morphology-based approach to a more functional approach with clinical implications. The classical histological patterns (trabecular, pseudoglandular, solid, etc.) are still taken into account but in combination with other parameters such as cell grading, clonal changes, type and extent of vascularisation, tumour immunophenotype etc. This array of morpho-phenotypical features is expected to ultimately provide information about cell of origin, tumour behaviour and, hopefully, treatment sensitivity. In this chapter we will give a brief overview on modern principles of hepatic carcinogenesis by outlining the events/lesions bridging the microscopic dysplasia to advanced HCC. In this context special emphasis will be given to novel concepts and diagnostics and differential diagnosis of small HCC (of early and progressed type), which is the main target of the surveillance in the cirrhotic population. Novel and emerging subpopulations of HCC will also be considered, for example HCC with stem/progenitor cell phenotype and mixed hepatobiliary forms which are filling the traditional separation between two entities (HCC and cholangiocarcinoma), likely more inter-related than previously thought.