Etiology, Pathogenesis, Diagnosis, and Practical Implications of Hepatocellular Neoplasms

Simple Summary In recent years, significant progress has been made in elucidating the mechanisms via which hepatocellular neoplasms, i.e., hepatocellular adenoma and hepatocellular carcinoma, arise. Hepatocellular carcinoma usually occurs in livers with chronic disease, due to deregulation of important intracellular pathways of signal transmission. Recent studies suggest that subclassification of hepatocellular carcinoma is practically useful. On the other hand, subclassification of hepatocellular adenomas has been well established through correlation of molecular alterations with morphology and protein expression. Advances in hepatic imaging have resulted in a new approach for diagnostic assessment of lesions arising in advanced chronic liver disease. Histologic examination, aided by immunohistochemistry, is the gold standard for the diagnosis and subclassification of hepatocellular neoplasms, while clinicopathologic correlation is essential for best patient management. We summarize the etiology and pathogenesis of hepatocellular neoplasms, provide practical information for their histologic diagnosis, and address various frequently asked questions regarding their diagnosis and practical implications. Abstract Hepatocellular carcinoma (HCC), a major global contributor of cancer death, usually arises in a background of chronic liver disease, as a result of molecular changes that deregulate important signal transduction pathways. Recent studies have shown that certain molecular changes of hepatocarcinogenesis are associated with clinicopathologic features and prognosis, suggesting that subclassification of HCC is practically useful. On the other hand, subclassification of hepatocellular adenomas (HCAs), a heterogenous group of neoplasms, has been well established on the basis of genotype–phenotype correlations. Histologic examination, aided by immunohistochemistry, is the gold standard for the diagnosis and subclassification of HCA and HCC, while clinicopathologic correlation is essential for best patient management. Advances in clinico-radio-pathologic correlation have introduced a new approach for the diagnostic assessment of lesions arising in advanced chronic liver disease by imaging (LI-RADS). The rapid expansion of knowledge concerning the molecular pathogenesis of HCC is now starting to produce new therapeutic approaches through precision oncology. This review summarizes the etiology and pathogenesis of HCA and HCC, provides practical information for their histologic diagnosis (including an algorithmic approach), and addresses a variety of frequently asked questions regarding the diagnosis and practical implications of these neoplasms.