In preclinical studies of pharmaceutical agents, the beagle dog is a commonly used model for the detection of cardiotoxicity. Incidental findings, postmortem changes, and artifacts must be distinguished histopathologically from test item-related findings in the heart. In this retrospective analysis, cardiac sections from 88 control beagles (41 male, 47 female; ages 5-18 months) in preclinical studies were examined histopathologically. The most common finding was thickening of the tunica media of intramural coronary arteries, most likely a postmortem change. The second most common finding was the presence of vacuoles within Purkinje fibers. Dilated lymphatic and blood vessels at the insertion of chordae tendineae were noted more commonly in males than in females and were considered a normal anatomic feature. Mesothelial-lined papillary fronds along the epicardial surface of the atria were present in several dogs, as were small infiltrates of inflammatory cells usually within the myocardium. In summary, control beagles' hearts frequently have incidental findings that must be differentiated from test item-related pathologic changes. Historical control data can be useful for the interpretation of incidental and test item-related findings in the beagle heart.
A 17-year-old Bengal tiger (Panthera tigris) presented with dyspnea and tachypnea. Radiographs revealed severe pleural and pericardial effusion, but no obvious mass. During attempts to remove the fluid under anesthesia, the cat developed cardiac tamponade and died. At necropsy, a nodular mass was found at the heart base and was identified as a pericardial mesothelioma. This is the first report of this tumor in any large cat.
In mice, hyaline droplets in renal proximal tubules have been associated with histiocytic sarcoma but have not been reported with lymphoma. Tissues from CD-1 mice in a 2-year carcinogenicity bioassay were examined microscopically. Twenty-five mice with hyaline droplets in renal tubules were identified. Immunohistochemistry to detect IgA, IgG, IgM, lysozyme, albumin, CD3, and CD79a was performed on kidneys of 21 affected mice. Hyaline droplets were present in the kidneys of 11 mice with lymphoma (1 male, 10 female), of which 1 female also had histiocytic sarcoma. Hyaline droplets were also present in 7 other mice with histiocytic sarcoma, 2 with chronic progressive nephropathy, 3 with renal cortical tubular necrosis, and 2 with granulocytic leukemia. Five of the 11 lymphomas were CD3þ, indicating a T lymphocyte origin. Hyaline droplets in mice with lymphoma did not stain for IgA, IgG, or IgM, except in one questionable case. Results of other immunohistochemical stains were inconclusive. Although the droplet composition could not be determined immunohistochemically, the study findings indicate that renal tubular hyaline droplets may be associated with lymphoma in mice.
Aneurysms of the ascending aorta, unrelated to xenobiotic administration, are described in 5 rats and 2 mice in nonclinical safety studies conducted at Charles River Laboratories (CRL) sites over the past 10 years. The most prominent microscopic finding was focal dilation with disruption of the wall of the ascending aorta with chronic adventitial inflammation or fibroplasia. The pathogenesis of this finding is unknown. There were no associated macroscopic findings, clinical abnormalities, or vascular lesions elsewhere. The results of a search of historical control data from toxicology studies of 1 day to 72 weeks’ duration performed at CRL for aortic findings from 5900 mice and 23,662 rats are also reported. Aortic lesions are uncommon in mice and rats used in nonclinical safety studies, but toxicologic pathologists should be aware that aneurysms of the ascending aorta with fibroplasia and inflammation in the aortic wall and adventitia may occur spontaneously or iatrogenically, as they have the potential to impact interpretation in toxicology studies.
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