Mineralized deposits detected in the cerebrum generally occur in the region of the medial, ventral and posterior thalamic nuclei (Morgan et al., 1983). They vary from single, rounded bodies up to 100 μm in diameter to very extensive, irregular, but usually rounded masses which in most cases are found to be associated with blood vessels (Figs. 9 and 328). The deposits exhibit faint to intense basophilia, and distinct concentric laminations are often evident. The most intense basophilia is associated with the larger deposits. The deposits stain negative for amyloid and iron, and are weakly positive with Alcian blue, the reaction being confined primarily to the periphery of the deposits. They stain densely dark brown-black with very distinct lamination by Verhoeff's method. Alizarin red stains them black at the periphery and faint red in the core.
The blood vessels in the thalamus with which the deposits appear to be associated are generally very thin-walled and of small caliber, being in many cases as large as or only slightly larger than capillaries. Examination of the thalamic deposits by electron microscopy reveals that they are brittle or hard, as they produce severe knife damage with subsequent scoring, especially in the case of larger, presumably more heavily mineralized deposits (Figs. 336 and 337).
X-ray microanalysis spectra have been obtained from selected representative regions including the dense peripheral zone of a large mineralized deposit, the shredded core of a large mineralized deposit and a small mineralized deposit (Morgan et al., 1983). Significant peaks for calcium and phosphorus were obtained from the dense peripheral zone of a large mineralized deposit (Fig. 338).
The inclusion cyst may occur rarely as a spontaneous lesion in the brain and spinal cord. Cysts range in size from very small to quite large, but the morphological appearance is similar. The cyst is lined by flattened squamous epithelium and is filled with eosinophilic desquaminated keratin (Figs. 329 and 330).
Hydrocephalus usually involves the lateral ventricles and is bilateral. The ventricles may be so enlarged as to cause a dome shape to the cranium. The sulci and gyri may be flattened and almost indiscernible in advanced cases. Microscopically, the ventricles are enlarged at the expense of the flattened cerebral cortex (Fig. 331).
This disease is genetic in origin and has only been reported in BALB/c mice (Morris et al., 1982; Shio et al., 1982). The disease is homozygous recessive and affected mice have a clinical progressive neurologic disorder. The disease is characterized by the accumulation of several sphingolipids in the reticuloendothelial cells of the liver, spleen and bone marrow. In the cerebellum, a marked decrease is evident in the number of Purkinje cells (Fig. 332), and some of the large neurons in the cerebrum present a distinct vacuolization of the cytoplasm (Fig. 333).
Vacuoles are a common entity in the white matter of the brains of mice, particularly in the cerebellum (Fig. 334). It has been suggested that this may be an artifact associated with the collection and processing of the brain. It has also been suggested that this may be a true lesion (Morgan et al., 1981) and may increase with age.
Infarcts are rare in the central nervous system, but occasionally occur in the cerebrum. They more commonly occur at the surface or less frequently deeper within the parenchyma (Fig. 335).
Tumors of the central nervous system of the mouse are extremely rare lesions (Morgan et al., 1984). The most common tumor is the oligodendroglioma which occurs in the cerebrum and/or diencephalon. It is usually ventro-lateral in location and involves much of the thalamus, hypothalamus and amygdaloid. The oligodendroglioma is comprised of a poorly demarcated mass of proliferating oligodendrocytes (Fig. 339) with variable degrees of neuronal satellitosis, nuclear palisading and mitoses. These cells have scanty cytoplasm, with, in some cases, a distinct perinuclear halo; the single round to oval nuclei are often hyperchromatic.
Astrocytomas occur much less frequently than oligodendromas in mice. The neoplasms are comprised of cells with indistinct cytoplasmic boundaries and large, oval or slightly folded nuclei (Fig. 340). The margins of the tumor mass are indistinct and there may be areas of edema, hemorrhage and microcystic damage. Hemorrhage and necrosis are seen more frequently in astrocytomas than in oligodendromas.
Lipomas have been seen associated both with the meninges and choroid plexus (Morgan et al., 1984). These consist principally of discrete, well-demarcated, small to large clusters or masses of mature adipocytes (Figs. 341 and 342). They may be present in the interstitium of the choroid plexus of the lateral ventricles and are extremely small (10 to 12 cells per section). Occasionally, small mass of cartilage-like material is present among the fat cells. The cell or tissue of origin of these lesions is unknown.
Tumors of the choroid plexus are rare. The one case described (Morgan et al., 1984) was a mass of about 2 mm in diameter which projected into the lumen of the third ventricle from a broad base. The neoplasm appeared to replace the choroid plexus in this location (Fig. 343). It was composed of cuboidal tumor cells with variable stroma and other pleomorphic areas.
Meningiomas also occur rarely in the mouse and can assume a variety of patterns as in other species. The tumor shown in Figure 344 is arising from the meninges at the base of the brain and is distinctly myxomatous in appearance. These neoplasms are comprised of a regular pattern of loosely interwoven bundles of delicate spindle cells, with single small hyperchromatic oval nuclei. The nuclei in some areas palisade in an irregular fashion. These cells lie in a faintly basophilic finely granular ground substance. In some cases, the neoplasms infiltrate the ventral brain along the adventitia of small blood vessels.
Hemangiosarcoma is a relatively frequently occurring tumor in the mouse, primarily in the spleen, liver and subcutaneous tissue. Two primary vascular tumors of the CNS have been previously reported, one in the thalamus and the other in the cerebellum (Morgan et al., 1984). They were large and appeared to be highly invasive, and were composed of small and large blood-filled, vascular channels lined by prominent endothelial cells (Fig. 345). A detailed search failed to reveal a primary neoplasm of this type elsewhere in these animals.
A single teratoma has been previously reported in the choroid plexus of the third ventricle (Morgan et al., 1984). It was about 2 mm in diameter and well demarcated. It consisted of an apparently random mixture of well differentiated tissues (Fig. 346) of both ectodermal and mesodermal origin, including epidermis with keratinized stratified squamous epithelium, striated muscle, adipose tissue, nerves and connective tissue.
Leukemia and lymphomas commonly metastasize to the brain. Mesenchymal tumors (sarcomas) may also occasionally spread to the brain.