Minute hepatoma with excessive copper accumulation. Report of two cases with resection

Minute hepatomas with prominent copper accumulations were resected in two women, aged 60 and 62 years, who had never suffered from jaundice. Mild elevation of serum alpha-fetoprotein level was found in both patients. One tumor was diagnosed by celiac angiography, and the other was determined by an ultrasonic echogram. Microscopically, these two tumors were relatively well-differentiated hepatocellular carcinoma, though having less-differentiated foci. Many cancer cells contained numerous copper granules stained by orcein, Victoria blue, and p-dimethylaminobenzylidene rhodanine. Ultrastructurally, cancer cells contained many secondary lysosomes with an electron-dense material. We concluded that the excessive copper in the cancer cells was aggregated lysosomal copper metallothionein, and that it might not be carcinogenic but stored by an altered metabolism of copper and copper-binding proteins with the neoplastic transformation.