Changing role of histopathology in the diagnosis and management of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common and fatal cancer in the world. HCC frequently presents with advanced disease, has a high recurrence rate and limited treatment options, which leads to very poor prognosis. This warrants urgent improvement in the diagnosis and treatment. Liver biopsy plays very important role in the diagnosis and prognosis of HCC, but with technical advancements and progression in the field of imaging, clinical guidelines have restricted the role of biopsy to very limited situations. Biopsy also has its own problems of needle tract seeding of tumor, small risk of complications, technical and sampling errors along with interpretative errors. Despite this, tissue analysis is often required because imaging is not always specific, limited expertise and lack of advanced imaging in many centers and limitations of imaging in the diagnosis of small, mixed and other variant forms of HCC. In addition, biopsy confirmation is often required for clinical trials of new drugs and targeted therapies. Tissue biomarkers along with certain morphological features, phenotypes and immune-phenotypes that serve as important prognostic and outcome predictors and as decisive factors for therapy decisions, add to the continuing role of histopathology. Advancements in cancer biology and development of molecular classification of HCC with clinic pathological correlation, lead to discovery of HCC phenotypic surrogates of prognostic and therapeutically significant molecular signatures. Thus tissue characteristics and morphology based correlates of molecular subtypes provide invaluable information for management and prognosis. This review thus focuses on the importance of histopathology and resurgence of role of biopsy in the diagnosis, management and prognostication of HCC.

Keywords: Hepatocellular carcinoma; Biomarker; Biopsy; Histopathology; Immunohistochemistry; Targeted therapy; Molecular; Diagnosis; Prognosis

Core tip: Liver biopsy plays important roles in the diagnosis and prognosis of hepatocellular carcinoma. However biopsy related complications and limitations along with advancements in imaging have restricted its role to very limited situations. In recent time, studies on tissue biomarkers, molecular classifications and targeted therapies for hepatocellular carcinoma (HCC) with their clinic-pathologic correlations have highlighted that morphologic variants and subtypes can serve as importance surrogates of molecular signatures, thus renewing the interest in tissue analysis. Tumor biopsy thus is increasingly being recognized as an invaluable tool for the diagnosis, management and prognostication of HCC.