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.

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