Pathology of early hepatocellular carcinoma: progression from early to advanced

Small, early stage hepatocellular carcinoma (HCC) can be divided into 2 types; small nodular HCC with distinct margins and small HCC with indistinct margins. The latter consists of well-differentiated cancerous tissue with replacing growth at the boundary and with many portal tracts retained in the tumor. When these tumors reach approximately 1.5-2.0 cm in diameter, moderately or poorly differentiated cancer tissues develop within the well-differentiated cancer tissue and well-differentiated cancer tissues are replaced by less differentiated cancer tissues. This dedifferentiation seems to be closely related to tumor proliferation. When less differentiated cancer tissues within the well-differentiated cancer nodules proliferate in an expansive fashion, a "nodule in nodule" appearance is frequently identified. On the other hand, small nodular HCCs with distinct margins are well-defined, with more than half of them encapsulated by a thin fibrous capsule, and about 60% moderately differentiated. Tumor invasion into the portal vein and intrahepatic metastasis are found in 27% and 10%, respectively. Thus, although the size of the tumor may be small, some distinctly nodular small HCCs can already be interpreted as advanced cancers.