Giant cell stromal reaction in squamous cell carcinomata. Electronmicroscopic and ultrahistochemical observations on the genesis and functional activity of multinucleated giant cells in bleomycin-induced tumor regression

Abstract

Ten cases of oral squamous cell carcinoma, treated by bleomycin, were studied by electron microscopy with particular regard to the stromal reaction. The genesis and phagocytic function of multinucleated giant cells of foreign body type were observed. These cells phagocytize devitalized, keratinized tumor cells in particular. Their genesis from monocytic macrophages and endocytosis of large keratinized tumor cells are described in detail. Both phenomena are connected and the mode of formation of the cells results in functional specialization. The initial stages of intracellular digestion do not seem to take place within membrane limited vacuoles but in specialized cytoplasmatic areas which are formed around the ingested material. These contain high concentrations of hydrolases, sealed off from the rest of the cell by a clear zone of organell-free cytoplasm. This unique form of phagocytosis and digestion ("gigantophagocytosis*) is only possible in these highly specialized giant cells and explains their biological significance. It is likely that secondary lysosomes are formed in subsequent stages of digestion. The difference between our results and the experimental observations of other authors are discussed.