Theory and practice of silver staining in histopathology

The special stains that utilize silver include various staining procedures that are based on very different principles. Five categories of silver stains can be defined by the physicochemical procedures involved. These are argentaffin methods, argyrophil methods, impregnation stains, silver oxidation-reduction stains, and metallic-metallic interactions (autometallography). For example, neuroendocrine cells can be identified by argentaffin or argyrophil techniques; whereas axons, neurofibrillary tangles, and senile placques are identified by silver impregnation techniques. Impregnation silver stains also can be used to demonstrate bacteria that are difficult to stain by other methods or to culture. Fungi, basement membranes, and reticulum can be stained with procedures in which oxidation of carbohydrates and glycoproteins is followed by reduction of silver by the oxidized molecule. The general principles underlying these silver staining techniques and their effective use are described in this manuscript.