Mineralization of the myocardium and epicardium occurs in various strains of mice as early as one month of age, and is more common in males than in females; it occurs most often on the right ventricle. Microscopically, the mineralized foci are characterized by distinctly basophilic areas after hematoxylin and eosin (H & E) staining (Fig. 2) by black areas when stained with von Kossa (Fig. 3) and red areas when stained with Alizarin Red (Fig. 4). The mineralization may be minimal or quite extensive covering most of the epicardial surface of the right ventricle. The mineralized areas may be surrounded by fibrosis, but an inflammatory component is minimal. The exact etiology is unknown but the lesion appears to have a genetic predisposition (DiPaola et al., 1964; Brownstein, 1983). The incidence of the epicardial mineralization in BALB/c mice at the NCTR was significantly higher in the male (10.5%) than in the female mice (3.6%) and increased slightly with age in both sexes (Frith et al., 1975). The incidence of spontaneous mineralization was much higher in the BALB/c mice than in other strains studied at the NCTR in which mice of similar age were subjected to comparable stress factors, environment and diet.
Mineralization of the myocardium is also a common lesion in a number of strains of mice (Rings and Wagner, 1972). The mineralized areas are focal and may involve the myocardium of both ventricles and the intraventricular septum. The atria are usually spared. The lesion appears to be a distinct entity and different from the epicardial mineralization. Microscopically the mineralized areas stain distinctly basophilic with H & E (Fig. 5). The focal areas of mineralization are often surrounded by fibrous connective tissue and a minimal infiltrate of mononuclear inflammatory cells is present. Myocardial mineralization (calcification) may be induced by low protein diets and mineral imbalance (Highman and Daft, 1951).
Atrial thrombosis is not a common lesion but occurs as both a spontaneous and an induced lesion in mice (Schieferstein et al., 1985). The thrombus more commonly involves the left atrium. Grossly, the involved atrium is enlarged and red. Microscopically, the distended atrium contains an organizing mural thrombus (Fig. 6). The degree of organization depends upon the age of the thrombus. Some of the thrombi may contain focal areas of cartilaginous metaplasia (Fig. 7). If the thrombi are large, they may lead to a secondary chronic passive congestion of the lungs. Thrombosis may be associated with uremia and kidney disease, including amyloidosis.
Medial hypertrophy involves an increase in the medial mass of small muscular arteries. The etiology of the medial hypertrophy is often obscure and the thickened vessels may be found in various organs. Microscopically it may be difficult to determine if the increased muscular mass is due to a hypertrophy or hyperplasia of the smooth muscle cells or merely represents a contraction of the vessel resulting in an apparent thickening but no increase of the muscle layer. The vessels often appear otherwise normal (Fig. 8).
Mineralization of the media of vessels occurs infrequently in mice compared to rats. It may involve the elastic fibers in the muscle wall of vessels in a variety of organs and stains intensely basophilic with H & E stain. Small thalamic vessels are one of the most common sites of involvement (Morgan et al., 1983). These areas of mineralization exhibit faint or intense basophilia, with distinct concentric laminations (Fig. 9).
Atherosclerosis is an extremely rare spontaneous lesion in mice. One author (CHF) has seen two cases. They occurred in the thoracic aorta and were characterized by a vacuolization within the thickened tunica intima (Figs. 10 and 11). Subintimal plaques have been reported in some mouse strains (Rehm et al., 1985b).
Polyarteritis in the mouse has been compared to periarteritis nodosa in man (Kumar, 1979). The etiology of both is unknown, but an immune origin is suspected. It is sometimes seen in Murine Lupus (Andrews, 1978) or may be associated with glomerulonephritis of unknown etiology (Ward et al., 1986b). In mice, the lesion involves small muscular arteries and is usually evident in multiple sites. Organs commonly involved include the heart, tongue, uterus, testes, kidney and urinary bladder. The media of the affected vessels is homogenous and intensely eosinophilic with H & E stain. Both fibrosis and an infiltration of mononuclear cells occur around the affected vessels (Fig. 12).
Angiectasis refers to a dilatation of vascular channels and usually is associated with lymphatics, veins or sinusoids. The lesion can occur in any organ but most commonly involves the spleen, ovary, liver or lymph nodes. The etiology and pathogenesis of angiectasis are often obscure. Angiectasis of the ovaries is an age-related change and is commonly associated with ovarian atrophy. Usually little normal ovarian parenchyma is present, but markedly dilated vessels engorged with erythrocytes are evident (Fig. 13). Hepatic angiectasis involves dilatation of the vascular sinusoids and may be either focal or diffuse (Fig. 14). Angiectasis must be distinguished from hemangioma, sometimes with difficulty. Portions of hemangiomas may appear as angiectatic lesions in some sections of the tumor. In angiectasis, the existing vascular spaces are dilated and prominent and their lining endothelial cells are normal in appearance, number and size.
Hemangioma and hemangiosarcoma are relatively common spontaneous and induced vascular tumors in mice (Frith and Wiley, 1982). Hemangiomas are characterized by a focal nodular proliferation of normal appearing vessels. They are commonly found in the uterus (Fig. 15) and may be visible grossly as small red nodules in the parenchyma of organs. The vessels are dilated and are lined by normal appearing, flattened endothelial cells. Besides the uterus, hemangiomas have also been seen in ovary, lymph nodes, liver, spleen, subcutaneous tissue, preputial gland and the urinary bladder.
The malignant counterpart of the hemangioma, the hemangiosarcoma, commonly involves a larger variety of organs. Hemangiosarcoma as primary neoplasms are seen in the subcutis, ovaries, mammary tissue, liver (Fig. 16), spleen, uterus and urinary bladder. The lesion may occur in multiple sites and it is sometime difficult to distinguish multicentric origin from secondary metastases (Fig. 17). The malignant endothelial cells are quite plump and form both solid sheets of anaplastic (undifferentiated cells) as well as vascular channels (capillary or cavernous) lined by better differentiated cells and filled with erythrocytes. Grossly, the neoplasm appears red because of the erythrocytes within the blood vascular channels.