Common Lesions and Incidental Findings in Laboratory Rodents Charles B. Clifford, DVM, PhD Senior Staff Pathologist Charles River Laboratories Introduction Pathologists are trained, intentionally and appropriately, to think of a complete list of differentials when faced with any given lesion. As training advances we are admonished to, "when you hear hoofbeats, think horses, not zebras". In real life, however, many lesions in modern laboratory rodents, i. e., the real "horses", are not included in the "classical" lists of differential diagnoses. Although each lesion surely has a specific cause, whether a metabolic derangement or a microbe, and although our job is to determined that cause, the morphologic appearance of the lesion is often non-specific. To further complicate matters, many lesions do not indicate the presence of a threat to the health of an individual animal, a colony of animals, or to the research in which they are used or intended. This discussion will cover a few of the lesions commonly encountered in diagnostic and routine health monitoring of laboratory rodents. Although some of these lesions can have individual health consequences, and can even be confounding factors in some studies, they are generally included under the broad category of incidental lesions. Many are significant only in that they must be distinguished from diseases on the traditional list of differential diagnoses. Mice Skin Lesions Bite Wounds and Claw Marks The most common skin lesion observed in mice housed or shipped in groups. Can appear as "epidemics" if mice are re-arranged, or stressed. Can be complicated by bacterial infection. Mostly on dorsum and tail. Follicular cysts in glabrous animals, immunodeficient and immunocompetent.. Nude and hairless mice develop cutaneous cysts, representing follicles distended with distorted hair shafts and keratinaceous debris. These may predispose to cutaneous abscesses subsequent to cyst colonization with opportunistic bacteria. Barbering Hair loss, often in patterns, usually without damage to skin. Usually affects multiple animals in a group. Mechanical hair loss may also be caused by some feeder designs. Dams may also chew whiskers or ears off pups. Streptococcosis Can cause cutaneous abscesses, pododermatitis, tail lesions. Can be systemic, with abscesses in heart, kidney, lung, etc. The systemic form is most frequently observed in animals soon after weaning, C3H and DBA mice seem affected most often, but no strain predilections have been documented in the literature. Preputial/Clitoral Gland Abscesses Variety of opportunistic bacteria common in environment are involved, Staphylococcus, Proteus, Pseudomonas, Pasteurella pneumotropica, E. coli, etc. Factors governing lesion development may related to bacterial concentration in bedding, and possibly to stress. Ringtail Cause not clear. Literature claims humidity/temperature. Affects neonates. Ocular Lesions Retinal Degeneration (light ) Well described in literature. Especially in albino strains/stocks. Primarily important to distinguish from genetic retinal degeneration, such as rd gene. Congenital and/or Genetic Eye Lesions (Retinal Dysplasia, Microphthalmia, Ectopic pupil) Vary with strain, retinal degeneration affects almost 100% of some strains. Internal Lesions Multifocal mineralization: heart, tongue, diaphragm Pale raised foci on the tongue, "frosted" appearance to the epicardium. Can also be within myocardium. Seen in DBA/2, BALB/c, occasionally in other mice. The pathogenesis of the lesion is unclear. No clinical effects. Splenic melanosis (C57BL6 mice) Not a lesion. Should not be confused with hemosiderosis or necrosis. Cardiomyopathy (C3H mice) Published once. Common in at least several lines of C3H. Can be fatal, especially in female breeders. Amyloidosis A leading cause of death in CD-1 mice. In order of likelihood to be affected: kidney, small intestine, mesenteric lymph nodes, gonads, liver, thymus, adrenals, salivary glands, spleen, heart. Cause and type (primary or secondary) not clear. Alveolar Histiocytosis Multifocal, usually sub-pleural, accumulations of foamy alveolar macrophages. Can be accompanied by some intersitial thickening and a few lymphocytes. Number and size of these accumulations increases with age. Eosinophilic Crystalline Pneumonia Accumulation of macrophages and granulocytes, with intracellular and extracellular eosinophilic, refractile, isotropic, elongate crystals. Most likely from bronchial/bronchiolar secretory product. "Idiopathic" Hepatic Necrosis in NIH Black mice One abstract. Nearly 100% incidence of perivascular necrotic foci. Not transmissible. Present in germ-free and SPF animals. Rats Skin Lesions (in addition to those in mice) Staphylococcosis Affects rats and other species, but rats seem most commonly affected. Can infect wounds, including minor wounds. Can appear as moist, ulcerative enlarging lesion behind the ear, and extending down the neck. Auricular Chondropathy Ocular Lesions Corneal Dystrophy Extremely high incidence in F-344 rats, although the incidence varies with sub-line. Can be associated with mild leukocytic infiltrate, but should not be mistaken for post- inflammatory scarring. If extensive, can obstruct ophthalmoscopic examination. May increase in severity with age. Porphyria The most common cause is mild dehydration during shipping. Can be observed after a number of non-infectious stresses, including elevated temperature. Can also be caused be a variety of infectious disease including mycoplasmosis and sialodacryoadenitis, although this occurs less frequently. Internal Lesions Pulmonary Granulomas in BN rats Not published. 25% incidence at 8 weeks of age of multifocal granulomatous pneumonia, with bronchiolar infiltration of eosinophils. Cardiomyopathy Progressive Renal Disease Hydronephrosis May be unilateral or bilateral, right kidney affected more often, males more often. Probably multigenic in some rats (Sprague-Dawley), single gene inheritance in others (Gunn rat). Pyelonephritis Can be due to any of a variety of Gram negative or Gram positive bacteria. Most often occurs in females, especially breeders. Lewis rats may have a higher incidence. White spots in the liver Presumed to be bacterial in origin, although cultures are generally negative. Histologically, these are most frequently characterized by accumulations less than 1 mm in diameter of mononuclear cells, with occasionally some neutrophils and a few centrally located degenerate hepatocytes. The lack of degenerate heatocytes at the periphery of the lesions, and the mild neutrophil infiltration suggests that the lesions are in a stage of regression. When cultures are positive, a variety of opportunistic bacteria may be found, as well as some bacteria often considered to be non- pathogenic. This suggests that these may be due to enteric organisms gaining access to the portal circulation, then being rapidly phagocytoses and killed in the liver. The activation of Kupffer cells might release sufficient cytokines to results in a small local accumulation of leukocytes. Some evidence suggests that there may be a slightly higher incidence soon after weaning. Guinea Pigs Skin Lesions ( in addition to those above) Age-related alopecia Commonly observed in older animals, especially boars. Hair becomes sparse, especially on flanks and on the back. This can also be seen in pregnant females, especially older ones. Similar changes are also observed in aged rats. Pododermatitis Common in older animals housed on wire. Ulcerated lesions on the weight bearing surface of the feet. Scrotal Plugs Common in older males. Not truly a lesion. Internal Lesions Segmental Nephrosclerosis Extremely common in older guinea pigs. Unknown cause. Distinguish from interstitial nephritis due to E. cuniculi by degree of fibrosis and virtual lack of leukocytic infiltration in segmental nephrosclerosis. Idiopathic Hepatic Necrosis Cause unknown. Most often subcapsular, may be extensive. Appearance is consistent with a hypoxic or ischemic cause. Older lesions may have some central mineralization and proliferation of cells at the periphery. Multifocal Mineralization May be spontaneous. May possibly be increased in Hypovitaminosis C. Pulmonary Foreign-Body (plant) Granulomas The most common grossly visible lung lesions in VAF guinea pig lungs. Osseous metaplasia in lung Occurs sporadically in guinea pigs and other species. References Faccini, J.M., Abbott, D.P., and Paulus, 1990, D.P.P., Mouse Histopathology, Elsevier, Amsterdam. Fox, J.G., Cohen, B.J., and Loew,F.M., 1984, Laboratory Animal Medicine, Academic Press, Inc., San Diego. Boorman, G.A., Eustis, S.L., Elwell, M.R., Montgomery,C.A., and MacKenzie, W.F., 1990, Pathology of the Fischer Rat, Academic Press, Inc., San Diego. Mohr,U., Dungworth, D.L., Capen, C.C., 1994, Pathobiology of the Aging Rat, Vols 1 and 2, ILSI Press, Washington, D.C. Percy, D.H., and Barthold, S.W., 1993, Pathology of Laboratory Rodents and Rabbits, Iowa State University Press, Ames.