Characterization and reclassification of titanium dioxide-related pulmonary lesions

Objective: Using current diagnostic criteria, this work summarizes microscopic review of 16 proliferative squamous lesions, previously diagnosed cystic keratinizing squamous cell carcinoma, in the lungs of rats from a 2-year inhalation study with pigment-grade titanium dioxide particles. Methods: In the aftermath of two international pathology workshops designed, in part, to establish histological criteria for classifying pulmonary keratin lesions, these lesions we evaluated by four pathologists using current diagnostic criteria. Results: Unanimous agreement was reached as to the diagnosis of each of the lesions. Two of lesions were diagnosed as squamous metaplasia and one as a poorly kerantinizing squamous cell carcinoma. The remaining 13 lesions were diagnosed as no neoplastic pulmonary keratin cysts. Conclusions: These keratin cysts are species-specific lesion that is unique to the rat lung under conditions of particle overload exposure.