Characterization and Reclassification of Titanium Dioxide-Related Pulmonary Lesions

Abstract

Using current diagnostic criteria, this work summarizes the microscopic review of 16 proliferative squamous lesions, previously diagnosed as cystic keratinizing squamous cell carcinoma, in the lungs of rats from a 2-year inhalation study with pigment-grade titanium dioxide particles. In the aftermath of two international pathology workshops designed, in part, to establish histological criteria for classifying pulmonary keratin lesions, these lesions were evaluated by four pathologists using current diagnostic criteria. Unanimous agreement was reached as to the diagnosis of each of the lesions. Two of the lesions were diagnosed as squamous metaplasia and one as a poorly keratinizing squamous cell carcinoma. The remaining 13 lesions were diagnosed as non-neoplastic pulmonary keratin cysts. These keratin cysts are a species-specific lesion that is unique to the rat lung under conditions of particle overload exposure.