Ultrastructural observations on preneoplastic epidermoid metaplasia in the lungs of rats

Epidermoid metaplasia, of a type that consistently progresses to epidermoid carcinoma, was induced in rats at the interface of pulmonary tissue and intrapulmonary deposits of beeswax that contained either benzo(alpha)pyrene or the heptane-soluble fraction of cigarette smoke condensate. The preneoplastic epithelium was searched for morphological harbingers of neoplasia and compared with the type of reactive bronchial metaplasia, rarely associated with cancer, that results from chronic murine pneumonitis. The carcinogen-laden beeswax caused both proliferation and migration of epithelial cells from bronchi adjacent to the wax deposits. These initial proliferating cells were characterized by a lack of differentiation and were similar to the basal cells of bronchial epithelium. The migrating epithelium rapidly established itself at the interface of wax and viable lung tissue as a highly differentiated, stratified squamous epithelium. This epithelium was not qualitatively different from normal squamous epithelium. However, quantitative differences were evident from both normal epithelium and the metaplastic epithelium resulting from nonspecific injury. In the preneoplastic epithelium, the first indications of aggressive behavior occurred in foci of dysplastic basal cells that sent cytoplasmic intrusions through defects in the basement membrane. Characteristically, these dyplastic basal cells had numerous infoldings of the nuclear membrane and prominent nucleolar alterations. All strata of preneoplastic cells contained excessively complex interdigitations of the plasma membrane and unusually large numbers of desmosomes and tonofilaments. In contrast, the nonspecific metaplastic epithelium consisted almost entirely of multilayered uniform cells that closely resembled immature but otherwise normal basal cells of respiratory epithelium.