In Wilson disease, hepatic copper levels are typically >250 μg/g (>4 μmol/g) dry liver weight. Staining for copper and copper-associated protein, however, is highly variable. In early stages, hepatic copper is diffusely distributed in hepatocytes and not concentrated in lysosomes, therefore histochemical stains (Timmís silver stain, rhodanine, or orcein) may show only faint cytoplasmic positivity. With disease progression, the copper accumulates in lysosomes and is more easily highlighted by histochemical stains. In cirrhotic livers, the copper is unevenly distributed: some nodules stain strongly while others are completely negative. Image Copyright: pathorama.ch.