Thymic Epithelial Hyperplasia and Thymoma in Control rasH2 Transgenic Mice From 26-Week Carcinogenicity Assays

Since the FDA's approval in 2003, transgenic rasH2 (Tg.rasH2) mice have been used as alternative models to assess the carcinogenic potential of new drug candidates. While several articles documenting spontaneous non-neoplastic and neoplastic findings in Tg.rasH2 mice have been published, the incidence and morphologic criteria of proliferative thymic epithelial lesions have not been discussed in detail. Here we report the incidence and diagnostic morphologic criteria of non-neoplastic (epithelial hyperplasia) and neoplastic (benign and malignant thymoma) proliferative findings in the thymus. Incidences were derived through a review of pathology data from 3948 male and female control Tg.rasH2 mice from sixty-three 26-week carcinogenicity studies conducted at Labcorp, Madison, WI, between 2012 and 2024. Compared with published literature, an increased incidence of epithelial hyperplasia was noted in both sexes, with a higher incidence noted in females (7.4%) versus males (3.4%). Benign thymomas occurred at a higher-than-published incidence in both sexes, being more frequent in females (1.8% in females vs 0.7% in males), and our data also documented the first occurrence of malignant thymoma in this mouse strain, which was also more common in females (1% in females vs 0.7% in males). The epithelial features of selected proliferative findings were confirmed by immunohistochemistry using pan-cytokeratin.