Spontaneous eosinophilic granulated round cell tumors in rats

Morphologic and histochemical characteristics were noted for three spontaneous tumors with eosinophilic cytoplasmic granules that occurred in aged Fischer 344 rats. Macroscopic lesions were widely distributed in the body, mainly involving the intra-abdominal adipose tissue, pancreas, and mesenterium. These lesions were generally hard swellings with nodular and sclerosing areas. Bloody ascites was a concomitant finding. Histologically, the tumor cells were round, from 9 to 30 microm in diameter with one or two round to oval nuclei, and characterized by eosinophilic granules (0.5-2.0 microm) that stained definitely to weakly positive with the periodic acid-Schiff reaction and demonstrated no metachromasia with toluidine blue stain. Furthermore, the granules were characterized by a positive reaction with lectin histochemistry for concanavalin A (Con A), wheat germ agglutinin (WGA), phaseolus vulgaris agglutinin (PHA-E4), lens culinaris agglutinin (LCA), and recinus communis agglutinin (RCA-I) in all tumors and for ulex europaeus agglutinin (UEA-I), peanut agglutinin (PNA), and soybean agglutinin (SBA) in one tumor. Positive reactions for anti-rat mast cell protease II and CD8 were not demonstrated immunohistochemically. Abundant glycogen was noted in the large tumor cells from one rat. With electron microscopy, the cytoplasmic granules were identified as electron-dense homogenous bodies bounded by a single unit membrane. These characteristics are similar to those of granulated metrial gland cells, but further study is needed to clarify the cell of origin for these tumors.     

Spontaneous tumors in domestic hamsters

A total of 90 tumors from 85 domestic hamsters (70 Djungarian hamsters and 15 Syrian hamsters) were examined by histology. In the Djungarian hamsters, 64 neoplastic and 11 non-neoplastic lesions were identified, whereas 14 Syrian hamsters showed neoplastic disease, and one showed non-neoplastic disease. The Djungarian hamsters showed a high prevalence of neoplastic disease, similarly to laboratory Djungarian hamsters. In the Djungarian hamsters, almost all tumors were integumental, whereas hematopoietic tumors were the most common type in the Syrian hamsters. The most common integumental tumors in the Djungarian hamsters were mammary tumors, atypical fibromas and papillomas, and a spectrum of integumental tumors that have not been reported in laboratory Djungarian hamsters were identified. Most mammary tumors occurred in the females, whereas all atypical fibromas were observed in the males. In the Syrian hamsters, plasmacytomas and lymphomas were the most common tumors. The small number of Syrian hamsters in this study may reflect the low prevalence of spontaneous tumors seen in laboratory Syrian hamsters. The mean age of the affected hamsters was 19.8 months, which is relatively advanced. To our knowledge, this is the first comprehensive study of tumors in domestic hamsters.     

Spontaneous tumors of small mammals.

The most common tumor of guinea pigs is bronchogenic papillary adenoma; of hedgehogs is mammary gland adenocarcinoma; of hamsters is adrenal cortical adenoma; of gerbils is ovarian granulosa cell and theca cell tumors; of mice is pulmonary carcinoma; and of rats is mammary fibroadenoma. A relatively low incidence of tumors is described for chinchillas and hamsters, whereas the incidence of tumors is high for gerbils, hedgehogs, mice, and rats. Limited literature regarding neoplasia exists for prairie dogs, sugar gliders, and chinchillas.     

Spontaneous thyroiditis in BB Wistar diabetic rats

Spontaneous lymphocytic thyroiditis was observed at necropsy in 36 BB Wistar diabetic rats (63.2%) and in eight of their nondiabetic siblings (42.1%). The incidence of thyroiditis decreased both with age and with longer duration of diabetes. All rats with pancreatic insulitis (a manifestation of the onset of diabetes) also had thyroiditis. BB Wistar rats with insulitis had more severe lymphocytic thyroiditis, characterized by lymphocytic, plasmacytic, and macrophage infiltration of thyroid interstitium and follicles. A milder, mostly perivascular and interstitial lymphocytic thyroiditis was characteristic of lesions in rats which did not have insulitis. The histological appearance of the thyroiditis suggests that these rats may be subject to autoimmune disease at the onset of diabetes which involves sites other than just the pancreas.     

Spontaneous ophthalmic lesions in young Sprague-Dawley rats.

Eight hundred eight Sprague-Dawley rats were examined for ophthalmic abnormalities during a pretest period in various preclinical safety assessment studies. Persistent pupillary membrane, corneal crystal, healed minor trauma, synechia, coloboma of the iris, lens luxation, cataract, persistent hyperplastic primary vitreous, vitreous hemorrhage, coloboma of the optic disc or choroid, remnant of hyaloid arterial system, retinal hemorrhage, retinal detachment, retinal folding and choroidal defect were observed. The incidences of corneal crystal, synechia, and nuclear cataract in this survey were higher than those reported previously. On the other hand, retinal folding in this survey was less common than that reported previously. These results suggest that background data of eye problems in albino rats should be accumulated in each own laboratory colony. In addition, since spontaneous eye problems are common in young albino rats, elimination of rats with ophthalmic abnormalities from study groups by an ophthalmic examination during a pretest period would facilitate to evaluate toxicity potential of test compounds in safety assessment studies.     

Spontaneous amelanotic melanomas of the uveal tract in F344 rats.

Five intraocular amelanotic melanomas were identified in the National Toxicology Program's database consisting of records from more than 60,000 female and 60,000 male F344 rats, which were used as control and treated animals in 2-year carcinogenicity studies. The five spontaneous melanomas were grossly observed as white or yellow, unilateral nodules, which originated in the region of the iris and ciliary body, often also involving the choroid. These amelanotic melanomas were composed predominantly of spindle cells arranged in a whorled pattern often with perivascular orientation. Mitotic figures were common in five tumors. The spindle cells had a positive immunoreactivity for S-100 protein but were negative for desmin. Electron microscopic studies provided clear evidence that these tumors originated from the uveal melanocytes. Ultrastructurally, the spindle cells contained numerous cytoplasmic premelanosomes (stage II melanosomes) that were not associated with melanin. Special histochemical studies showed that the spindle cells had a negative reaction for melanin. Although electron microscopic features are critical in the diagnosis of amelanotic melanomas of the uveal tract, the whorled pattern of spindle cells is a useful histologic criterion in differential diagnosis of this tumor in F344 rats.     

Spontaneous basophilic hypertrophic foci of the parotid glands in rats and mice

Basophilic hypertrophic foci of the parotid glands characterized by focal hypertrophy and hyperchromasia of acinar cells was seen in Sprague-Dawley rats and Swiss mice with overall incidences of 4.8% (102/2,138) and 0.6% (4/723), respectively. In rats, the incidence increased significantly with age, but the size and number of the lesions per rat did not. Based on the similar incidence in both control and treated animals, lesions were considered to be spontaneous. Their morphology and growth pattern suggested that they were neither degenerative, necrotic, hyperplastic/preneoplastic, nor neoplastic, but, that they are a distinct pathologic entity of a nature not yet determined.     

Spontaneous nonthymic T cell lymphomas in young Wistar rats

Spontaneous acute lymphomas and related leukemias, occurring in three of 2,974 male Wistar rats used as controls in toxicity studies during the last 14 years (1974-1987), were examined by light and electron microscopy and by using immunohistochemistry. At autopsy, conspicuous hepatosplenomegaly was noted. Morphologically, tumor cells of all three rats were medium-sized lymphocytes with many mitotic figures proliferating mainly in the spleen, liver, and bone marrow. Virus-like particles were not detected. Immunohistochemically, almost all tumor cells were positive for thy-1 antigen but negative for hematopoietic and differentiation markers such as W3/13, W3/25, OX4, OX8, and OX12. The results suggest that the lymphomas in these three rats were derived from T cells.     

Spontaneous pathology of the thymus in aging Wistar (Cpb:WU) rats

Spontaneous thymic lesions were investigated in Wistar (Cpb:WU) rats. Thymic tumors were not uncommon and most showed medullary differentiation. Thymic involution was investigated in a limited group of animals in which the survival rate for males and females was similar. The histological pattern of thymic involution differed between sexes. Severe thymic involution occurred more frequently in males than in females and at an earlier age.     

Amelanotic melanocytic tumors of the pinna in six F344 rats.

Spontaneous amelanotic melanocytic tumors of the pinna were found in six females of 960 male and 960 female albino (F344/DuCrj) rats which had been used in three different 24-month chronic toxicity studies. The age when the pinnal tumors were detected ranged from 37 to 59 weeks. The tumors were located unilaterally in the pinna and observed as subcutaneous spherical to irregular, solid white masses measuring 7 to 25 mm in diameter. The pinnal tumors were histologically classified into spindle cell and pleomorphic cell types. The spindle cell type was observed in four rats and composed of fusiform cells arranged in interlacing bundles. The pleomorphic cell type was observed in the remaining two rats and composed of pleomorphic large cells arranged in sheets. One tumor of the latter type metastasized to the submaxillary lymph node and lung. Melanin pigments were not demonstrated in any of the tumors. In immunohistochemistry, nuclei and cytoplasm of tumor cells in all the tumors were slightly positive for S-100 protein. Ultrastructurally, tumor cells contained a considerable number of premelanosomes in the cytoplasm. Desmosomes were occasionally observed between the cell membranes of the adjacent tumor cells. No distinct basal lamina was seen around tumor cells.