Incidence and characterization of spontaneous pituitary neuroendocrine tumors in aged spontaneously hypertensive rats

Primary intracranial tumors make up ~ 2% of all cancer cases but contribute disproportionately to cancer-related morbidity and mortality. While spontaneous preclinical intracranial tumor models offer valuable insights into the mechanisms underlying primary tumor formation and progression, few have been identified to date. As such, tracking and characterizing spontaneous tumor development in aging laboratory animals represents an opportunity to advance preclinical research, while informing best practices for animal welfare. Here, we investigated intracranial tumor incidence and origin in a cohort of spontaneously hypertensive rats aged 20-24 months (SHRs; N = 60), initially intended for preclinical stroke experiments. Upon gross inspection, we identified large intracranial tumors in 30% of aged SHRs. Using histological, immunohistological, and ultrastructural methods, we found that ~ 89% of these tumors were pituitary neuroendocrine tumors (NETs), with an average tumor diameter of 6.7 ± 1.22 mm (mean ± 95% confidence interval). These pituitary NETs displayed rapid growth, invasive behavior, and aggressive proliferation, as indicated by Ki67 staining. Our results reveal a predisposition in aged SHRs to develop aggressive pituitary NETs, providing a diagnostic and pathological foundation for future mechanistic and translational studies, while emphasizing the need for enhanced surveillance and care in aging laboratory animal populations.