Spontaneous squamous cell carcinoma of nasal and paranasal structures in the Cpb:WU (Wistar random) rat : nasolachrymal duct as major site of origin

Spontaneous nasal tumors in ageing rats are very rare. Chronic irritation and disruption of nasal, paranasal, buccal, and dental tissues have been associated with the occurrence of tumors of the nasal and paranasal structures in rats. To find out whether there is a relationship between malocclusion (MO) and nasal squamous cell carcinoma (SCC) in Cpb:WU (Wistar random) rats, a total of 899 untreated control rats (548 males and 351 females) from eight long-term toxicity/carcinogenicity studies was screened for nasal tumors and MO. All relevant data and the histopathology of the nasal and paranasal structures of a sample of these rats (189 males and 197 females from three of the studies) and all rats bearing a nasal tumor were subjected to a detailed analysis. Of the 899 rats, 84 males (15%) and 78 females (22%) suffered from MO. Microscopic examination revealed an unexpectedly high incidence of lesions in the nasolachrymal duct (NLD): 64 out of 189 males (34%) and 68 out of 197 females (34.5%) showed inflammatory changes, with or without squamous metaplasia and/or hyperplasia of the lining epithelium of the NLD. The incidence of NLD lesions was much higher in the animals with than without MO, suggesting an interaction of both phenomena. Eight of the 899 untreated control rats had a nasal tumor; all were SCCs and all occurred in males. The origin of the tumors was as follows: 2 NLD, 2 most probably NLD, 2 presumably NLD, 1 of unknown origin but possibly NLD, and 1 probably a cutaneous epidermoid cyst. On the basis of these findings, it was concluded that nasal SCC in Cpb:WU (Wistar random) rats prevails in males and is primarily associated with chronic inflammation of the NLD rather than with MO, although MO probably is an (indirectly) contributing factor.