Histopathologic evaluation of hepatocellular carcinoma with special reference to small early stage tumors

Over the past decade extensive studies on small early stage hepatocellular carcinomas (HCCs) have defined their pathomorphologic features. Most early HCCs are well differentiated, with an ill-defined nodular appearance. Proliferation of well-differentiated small HCCs is closely related to tumor dedifferentiation. When a well-differentiated HCC reaches a size of about 1.0-1.5 cm in diameter, less-differentiated cancerous tissues with greater proliferative activity evolve within it. Such a phenomenon is often appreciated grossly and/or histologically as a "nodule-in-nodule" appearance. Subsequently, moderately to poorly differentiated HCC tissues gradually replace the initial surrounding HCC. This replacement of well-differentiated HCC tissue is completed when the tumor reaches a size of about 2-3 cm. Hyperplastic nodular lesions in cirrhotic livers may have a premalignant potency. HCC frequently occurs multicentrically whether synchronously or metachronously, defying complete cure by conventional therapies other than liver transplantation.