The Histopathology and Ultrastructure of Pleural Mesotheliomas Produced in the Rat by Injections of Crocidolite Asbestos

Primary tumours of the pleural cavity were produced in rats by the intrapleural injection of crocidolite asbestos. Their histological structure as seen with both light and electron microscopy was very variable and tumours frequently contained elements of both connective-tissue and epithelial type. In some instances the connective-tissue elements predominated from the start and the earliest tumour nodules consisted mainly of pleomorphic connective-tissue cells with only a few layers of cells more nearly epithelial in type on the surface. This pattern was largely retained when tumour nodules increased in size and coalesced, but in the deeper layers of advanced tumours the pleomorphic connective-tissue pattern was often replaced by a more uniform spindle-cell form. Other tumours were more predominantly epithelial in type, showing either a papillary pattern with rounded epithelial cells growing in solid columns, or a vesicular form in which large tissue spaces, often intracellular, were lined by very thin layers of extended cell cytoplasm. Whereas early tumours showed only one histological pattern, the more advanced stages often exhibited areas of all 3, so that there seemed to be some degree of histological mutability. The spindle-cell areas of advanced tumours frequently showed evidence of direct invasion of the surrounding tissue but this was never seen with the epithelial forms of rat mesothelioma.