Histological and morphometrical indicators for a biopsy diagnosis of well-differentiated hepatocellular carcinoma

Among 597 patients with nodular hepatic lesions who underwent ultrasonically guided needle biopsy, 305 were histologically confirmed as having hepatocellular carcinoma, and 37 patients had borderline lesions. Histological reexamination was correlated with morphometrical analysis on selected cases of well-differentiated, microtrabecular hepatocellular carcinomas (n = 29), borderline lesion (n = 10), typical (mid-sized and macrotrabecular) hepatocellular carcinomas (n = 15) and cirrhotic liver tissue obtained from extranodular hepatic parenchyma of hepatocellular carcinoma patients (n = 47). Morphometrical analyses revealed that the mean cell size and nucleocytoplasmic ratio were most useful for distinguishing well-differentiated, microtrabecular hepatocellular carcinoma from cirrhosis. These two parameters were well correlated with nuclear density. The grade of nuclear density, therefore, seemed to be a convenient semiquantitative indicator for diagnosing well-differentiated hepatocellular carcinoma. A comparison between intranodular and extranodular hepatic tissues was particularly important for its assessment. It is concluded from the results that hepatic nodules presenting a nuclear density larger than two times that of controls could be classified into the overt hepatocellular carcinoma group. From the statistical aspect, the possibility of microtrabecular hepatocellular carcinoma should be considered when a nodule has a nuclear density exceeding 1.3 times that of the extranodular tissue.