'Nodule-in-nodule' appearance in hepatocellular carcinoma: its significance as a morphologic marker of dedifferentiation.

Small hepatocellular carcinoma (HCC) of the early stage can be divided into 2 types: small nodular HCC with distinct margins and small HCC with indistinct margins. The latter consists uniformly of well-differentiated cancerous tissue with a replacing growth at the boundary, and many portal tracts are retained in the tumor. When such tumors reach around 1.5-2.0 cm in diameter, moderately or poorly differentiated cancer tissues develop within the well-differentiated cancer tissue, and well-differentiated cancerous tissues are replaced by less differentiated cancerous tissues. Such a dedifferentiation seems to be closely related to tumor proliferation. When less differentiated cancerous tissues within the well-differentiated cancer nodules proliferate in an expansive fashion, a 'nodule-in-nodule' appearance is frequently seen. Thus, a 'nodule-in-nodule' appearance in early-stage HCC could be interpreted as a morphologic marker of dedifferentiation of early HCC.