Morphologic characterization of spontaneous nervous system tumors in mice and rats.
Spontaneous rodent nervous system tumors, in comparison to those of man, are less well differentiated. Among the central nervous system (CNS) tumors, the "embryonic" forms (medulloblastoma, pineoblastoma) occur both in rodents and humans, whereas the human "adult" forms (gliomas, ependymomas, meningiomas) have fewer counterparts in rodents. In general, the incidence of spontaneous CNS tumors is higher in rats (>1%) than in mice (>0.001%). A characteristic rat CNS tumor is the granular cell tumor. Usually it is associated with the meninges, and most meningeal tumors in rats seem to be totally or at least partly composed of granular cells, which have eosinophilic granular cytoplasm, are periodic acid-Schiff reaction (PAS)-positive, and contain lysosomes. Such tumors are frequently found on the cerebellar surface or at the brain basis. Rat astrocytomas are diffuse, frequently multifocal, and they invade perivascular spaces and meninges. The neoplastic cells with round to oval nuclei and indistinct cytoplasm grow around preexisting neurons, producing satellitosis. In large tumors, there are necrotic areas surrounded by palisading cells. Extensive damage of brain tissue is associated with the presence of scavenger cells that react positively with histiocytic/macrophage markers. The neoplastic astrocytes do not stain positively for glial fibrillary acidic protein; they probably represent an immature phenotype. In contrast to neoplastic oligodendroglia, they bind the lectin RCA-1. Astrocytomas are frequently located in the brain stem, especially the basal ganglia. Rat oligodendroglial tumors are well circumscribed and frequently grow in the walls of brain ventricles. Their cells have water-clear cytoplasm and round, dark-staining nuclei. Atypical vascular endothelial proliferation occurs, especially at the tumor periphery. Occasionally in the oligodendrogliomas, primitive glial elements with large nuclei occur in the form of cell groups that form rows and circles. Primitive neuroectodermal tumors of rats, such as pineal tumors or medulloblastomas, appear to have features similar to those found in man. In mice, the meningeal tumors are mostly devoid of granular cells and the astrocytomas are similar to those occurring in rats, whereas spontaneous oligodendrogliomas are observed extremely rarely. Tumorlike lesions, such as lipomatous hamartomas or epidermoid cysts, are occasionally encountered in the mouse CNS. It is suggested that we classify rodent CNS lesions as "low grade" and "high grade" rather than as "benign" and "malignant." The size of CNS tumors is generally related to their malignancy. Tumors of the peripheral nervous system are schwannomas and neurofibromas or neurofibrosarcomas consisting of Schwann cells, fibroblasts, and perineural cells. Well-differentiated schwannomas are characterized by S-100 positivity and the presence of basement membrane. They show either Antoni A pattern with fusiform palisading cells or Antoni B pattern, which is sparsely cellular and has a clear matrix. The rat develops specific forms of schwannomas in the areas of the submandibular salivary gland, the external ear, the orbit, and the endocardium. Spontaneous ganglioneuromas occur in the rat adrenal medulla or thyroid gland. Compared to experimentally induced neoplasms, the spontaneous tumors of the rodent nervous system are poor and impractical models of human disease, although they may serve as general indicators of the carcinogenic potential of tested chemicals.
Krinke
G J
GJ
Toxicology Department, Novartis Crop Protection AG, Stein, Switzerland. georg.krinke@cp.novartis.com
Kaufmann
W
W
Mahrous
A T
AT
Schaetti
P
P
D000818:Animals; D051379:Mice; D009423:Nervous System Neoplasms / Q000473:pathology*; D051381:Rats