No abstract

Abstract. A 10.25-year-old female beagle had an invasive neoplasm at the base of the heart which metastasized to the lungs, pancreas, and kidney. The neoplasm in these locations was composed of clusters of polyhedral cells surrounded by fine fibrovascular stroma. The differential diagnoses were malignant chemodectoma, ectopic parathyroid carcinoma, and ectopic thyroid carcinoma. Based on ultrastructural features, this tumor was an ectopic thyroid carcinoma.The differential diagnosis for primary benign and malignant tumors at the base of the heart in dogs includes aortic body tumors (chemodectomas), ectopic parathyroid gland tumors, and ectopic thyroid gland tumors [3]. Malignant chemodectomas are the only heart-base tumors for which there are previous reports of distant metastasis [2-7, 101. We describe a carcinoma of ectopic thyroid glandular tissue, in a laboratory beagle, which originated at the base of the heart and metastasized widely. Case HistoryA 10.25-year-old female beagle was one of 120 dogs that received 83 rads of total body "CO gamma radiation in utero at day 55 of gestation. The experimental design and dosimetric data for this experiment have been published [l]. The dog had anterior cervical edema with abnormal radiographic densities throughout the lungs and around the base of the heart. Abnormal heart motion and thickening of the pulmonary artery and left ventricular wall were detected by echocardiography. Electrocardiographic conduction disturbances also were present. The dog was killed and a thorough postmortem examination was done. Materials and MethodsGross lesions and representative samples of all major body organs were collected and fixed in 10% neutral buffered formalin, embedded in paraffin, sectioned at 6 pm, and stained with hematoxylin and eosin (HE). Sections of neoplasms also were stained with periodic acid-Schiff (PAS). Representative samples of the masses at the base of the heart and in the left kidney were fixed in 2.5% glutaraldehyde, postfixed in osmium tetroxide, and embedded in epoxy

Membranous nephropathy, a disease syndrome characterized by severe proteinuria and often accompanied by the nephrotic syndrome, was identified in 29% of a population of 46 proteinuric dogs. Renal lesions were characterized by the presence of subepithelial immunoglobulin deposits distributed diffusely along the glomerular capillary wall. Advanced stages were associated with progressive thickening of capillary basement membranes and incorporation of the immune deposits. These changes were followed by either glomerulosclerosis or recovery. Characteristic morphologic stages were correlated with clinical pathologic findings which showed that the level of proteinuria, hypoalbuminemia, and consequent nephrotic syndrome was most severe in the initial stages of membranous nephropathy while the level of azotemia increased in the more advanced stages of the syndrome.

Both kidneys of 12 mature female pigs received either a single dose of 9.8 Gy 60Co gamma rays or sham irradiation. At intervals of 1-4 weeks serial renal biopsies were obtained, followed by sacrifice at 24 weeks after irradiation. Individual kidney glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and the hematocrit (Hct) were measured routinely. Renal irradiation resulted in a progressive decline in GFR, ERPF, and Hct, with minimal values being observed within 12 weeks of irradiation. No change in any of these parameters was noted in the sham-irradiated pigs. The initial morphological change in irradiated glomeruli was leukocyte attachment to capillary endothelial cells 3-6 weeks after irradiation followed by activation and swelling of the endothelial cells. This was followed by pronounced increases in capillary permeability with fluid and erythrocyte, leukocyte, and platelet exudation into the subendothelial/mesangial space. This resulted in compression of glomerular capillary lumina, which occurred concomitantly with the reduction in GFR. By 12 to 15 weeks after irradiation the changes in endothelial cells were less evident. However, mesangial cells exhibited evidence of activation and proliferation accompanied by progressive mesangial expansion and sclerosis. Thus the glomerular capillary endothelial and mesangial cells appear particularly important in the pathogenesis of radiation nephropathy.

The protective activity of the bisdioxopiperazine ICRF-187 against the cardiotoxicity of doxorubicin was evaluated in the rat using both functional and histological assays. Animals that had received a single i.v. dose of doxorubicin (4 mg/kg) alone were compared with those that had been pretreated with a single i.v. injection of saline or ICRF-187 (40 or 60 mg/kg). All rats showed a transient reduction in body weight during the first 3 weeks after drug administration. The greatest reduction (approximately 16%) was observed in animals that had received a combination of ICRF-187 (40 or 60 mg/kg) and doxorubicin. Deaths related to cardiotoxicity were observed only in rats that had received doxorubicin alone and in those treated with saline; most of the deaths occurred at between 8 and 13 weeks after drug administration. Sequential assessments of heart function showed a persistent depression of cardiac output in animals that had received doxorubicin, with or without pretreatment with ICRF-187. The reduction in cardiac output observed in rats that had been pretreated with ICRF-187 (40 or 60 mg/kg) amounted to approximately 15% and approximately 30% after 12 and 20 weeks, respectively, indicating that cardioprotection was only partial. Nevertheless, this represented a marked improvement as compared with the approximately 35% reduction in cardiac output measured at 12 weeks in animals that had received doxorubicin but without pretreatment with ICRF-187. Histological examination of animals that had died during the course of the study and had received doxorubicin after pretreatment with saline revealed severe myocardial lesions typical of doxorubicin-induced damage. In contrast, animals that had been pretreated with ICRF-187 and survived for up to 20 weeks after treatment showed a marked amelioration of these lesions. The present findings may be interpreted as a true cardioprotection or a delay in the onset of the cardiotoxicity of doxorubicin resulting from pretreatment with the bisdioxopiperazine ICRF-187. Although prior and ongoing clinical trials clearly indicate that ICRF-187 protects patients well against doxorubicin-induced heart damage, further investigations are required before high doses of ICRF-187 can be used as a means of increasing the protective activity of this drug against doxorubicin-induced cardiotoxicity.