Morphological precursors of hepatocellular carcinoma: a morphometrical analysis

Morphometrical analysis of different types of liver cells was performed in cases of chronic active hepatitis (CAH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). The area and a form factor (form AR) of nuclei and cytoplasms were determined, and the nucleo-cytoplasmic ratio (N/C) was calculated in normal hepatocytes, HBsAg-positive cells, large dysplastic cells, cancer cells and in a liver cell population identifiable as "small dysplastic cells" (small cells). The nucleo-cytoplasmic ratio of the small cells and of the neoplastic cells was roughly the same and the highest. Large dysplastic cells showed a small nucleo-cytoplasmic ratio, almost comparable with that of normal hepatocytes and similar to that of HBsAg-positive cells. Since cellular precursors of liver cancer are expected to have a nucleo-cytoplasmic ratio similar to that of neoplastic cells, our morphometrical evaluation indicates small cells as the true precancerous cells; liver cell dysplasia (large dysplastic cells), as described by Anthony et al., should not be considered as a true preneoplastic change.