The strengths and weaknesses of gross and histopathological evaluation in hepatocellular carcinoma: a brief review

Abstract

Careful pathological analysis of hepatocellular carcinoma (HCC) specimens is essential for definitive diagnosis and patient prognostication. Tumor size and focality, gross patterns, macro- and microvascular invasion, degree of histological differentiation and expression of Keratin 19 (K19) are relevant features for risk stratification in this cancer and have been validated by multiple independent cohorts. However, there are important limitations to pathological analyses in HCC. First, liver biopsies are not recommended for diagnosis according to current clinical guidelines. Second, there is limited morphological data from patients at intermediate, advanced and terminal disease stages. Finally, there is little consensus on the evaluation of key histopathological features, notably histological grading (degree of differentiation). Here, we review important morphological aspects of HCC, provide insights to molecular events in relation to phenotypic findings and explore the current limitations to pathological analyses in this cancer.