Ultrastructural characteristics of carcinogen-induced dysplastic changes in tracheal epithelium

Squamous metaplasias with various degrees of atypia, carcinomas in situ, and microinvasive carcinomas produced in rat tracheal transplants by a 4-week exposure to demethylbenz(a)anthracene were studied 12-96 weeks after cessation of carcinogen exposure. In addition to the classical nuclear and cytoplasmic indicators of atypism, the squamous metaplasias with slight and moderate atypia were characterized by the presence of glycogen in the spinous layer, atypical composite keratohyalin granules in the granular layer, and in most cases an orthokeratinized horny layer. The squamous metaplasias with severe atypia showed an increased secretory activity and a decreased number of desmosomes. Carcinomas in situ were characterized by numerous intracellular and extracellular microcysts filled with secretory material identified by histochemical techniques as containing neutral glycoproteins and sialomucins. Microinvasive carcinoma showed similar characteristics, with an increase in polylobulated nuclei and appearance of multilaminar ergastoplasm. An outstanding feature in all these lesions was the presence of dark fusiform epithelial cells. They were observed in the middle layers in the squamous metaplasias with severe atypia and appeared in all layers of the carcinomas in situ.