Reactions of Connective Tissues After Protracted Fractionated Irradiation of Laryngeal Carcinoma

Abstract

With increasing experience in protracted fractionated irradiation, it has been thought that one of the advantages of this method is that the connective stroma remains functionally and also morphologically almost unaltered, and that this is responsible to a large extent for the improved radiation effects. Clinical observations, however, of the fibrin reaction of the mucous membrane in the early stages of protracted fractionated irradiation, and of the atrophy, sclerosis, edema, and necrosis of connective tissue in later stages, are contradictory to this view. Thus it seems justified to describe microscopic findings on the connective tissue observed in the larynx one to ten months after protracted fractionated irradiation. At the time of fibrinous epithelitis, the connective tissue is definitely altered. Absence or irregularity of nuclear staining, large nuclei, vacuolization of the cytoplasm, and fatty degeneration are exhibited microscopically. In this stage, various amounts of fibrin are present in the subepithelial and deep connective-tissue layers (Fig. 1). The changes are less advanced than those in the epithelial cells, which are completely disintegrated at the time of the fibrinous radiomucositis. One to two months after irradiation, the most frequent change in the connective tissue is a fibrinoid necrosis. This is best demonstrable with Weigert fibrin stains. With ordinary methods of staining, it is not recognizable as such. In some cases, one may later observe transition of areas of fibrinoid necrosis into colliquation, and spotty disintegration of the involved structures. On the other hand, a transformation into hyaline sclerotic scar tissue is often seen. In the latter cases, the entire lamina propria of the larynx becomes atrophic to such an extent that the glands seem to be located immediately below the regenerated epithelium, due to the atrophy of connective layers (Fig. 2). The elastic fibers lie close to each other in such conditions. Necrotic areas of the connective tissue are located chiefly in the internal layer, near the lumen. This suggests that, in addition to the direct effects of radiation, there may be secondary accidents precipitating retrogressive connective-tissue changes. The almost constant finding of fusiform bacilli and of gram-positive cocci in disintegrated connective tissue indicates that secondary infections progressing from the lumen may play an important role in the development of such changes. The boundaries of the necrotic areas often display characteristic retrogressive nuclear changes and also a mild lymphoid cellular reaction. After more intense irradiation, lymphoid cells may be absent, the boundaries of the necrotic areas being marked only by a zone of nuclei in all stages of karyorrhexis, pyknosis, and karyolysis.