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It is generally said that neoplastic cells are immunohistochemically negative for glial fibrillary acidic protein (GFAP) in rat spontaneous astrocytomas, and there are no reports describing the existence of GFAP-positive neoplastic astrocytes in rat spontaneous oligodendrogliomas and mixed gliomas which contain neoplastic astrocytes. In the present study, to clarify whether GFAP-positive neoplastic astrocytes exist in rat spontaneous oligodendrogliomas and mixed gliomas or not, immunohistochemical examination was performed on spontaneous oligodendrogliomas (26 cases) and mixed gliomas (5 cases) collected from the carcinogenicity studies and short-term toxicity studies. The neoplastic cells that constitute oligodendrogliomas and mixed gliomas were morphologically classified into five types: round A, round B, round C, spindle, and bizarre. The cells of round A, B, and C types were thought to be neoplastic oligodendrocytes because of their positive immunostainability for Olig2.  The origin of bizarre cells was obscure because they were negative for Olig2, GFAP, and nestin. The spindle cells were considered to be neoplastic astrocytes, because some of them were positive for GFAP or nestin, and GFAP-positive spindle cells could be morphologically distinguished from reactive astrocytes.  In conclusion, the present study clarified for the first time that GFAP-positive neoplastic astrocytes exist in rat spontaneous gliomas. [ABSTRACT FROM AUTHOR]

Busulfan, an antineoplastic bifunctional-alkylating agent, is known to induce developmental anomalies. In the present study, we examined the distribution and sequence of pyknotic cells in rat fetal tissues exposed to busulfan. Pregnant rats on gestation day 13 were administered intraperitoneally 30 mg/kg of busulfan, and fetal tissues were examined at 6, 12, 24, 36, 48, 72 and 96 hours after treatment (HAT). Pyknosis of component cells was observed markedly in the brain, moderately in the eyes and spinal cord and mildly in the craniofacial tissue, mandible, limb buds, tail bud, ganglions, alimentary tract, lungs, kidneys, pancreas and liver. In the brain, mitotic inhibition was also detected. Most of the pyknotic cells were considered to be apoptotic cells judging from the results of TUNEL staining and electron microscopic examination. Commonly in the above-mentioned tissues, pyknotic cells began to increase at 24 HAT, peaked at 36 or 48 HAT and disappeared at 96 HAT, which is when the histological picture returned to normal in most tissues except for the brain, spinal cord and eyes. The present study clarified the outline of busulfan-induced apoptosis in rat fetuses. [ABSTRACT FROM AUTHOR]

Among spontaneous neoplasms of the rat central nervous system, the discrimination between astrocytoma and malignant reticulosis (MR) is sometimes difficult because of their similar cell morphology and infiltration patterns. In the present study, we carried out histological and immunohistochemical analyses on a total of sixty-four cases in Sprague-Dawley and F344 rats. These cases were diagnosed as benign/malignant astrocytoma containing no neoplastic oligodendroglial elements or MR according to the diagnostic criteria of the World Health Organization International Classification of Rodent Tumors (Mohr et al. 1994). Astrocytomas were divided into three types and MR into two types based on the number of lesions, cellularity and infiltration patterns, and so on. Although the neoplastic cells from all types showed various immunoreactivities for RM-4 (anti-rat macrophages and dendritic cells), ED-1, and/or vimentin, there were no distinctive differences among these types, and most cells that were positive for RM-4 were also positive for ED-1. None of the tumor types showed any reactivity for GFAP or S-100 protein. From the results of morphological and immunohistochemical examinations, it was indicated that there are no distinctive differences between spontaneous astrocytomas and MR in rats, and they are probably derived from the same cell lineage, that is, microglia, macrophage, or radial glia. [ABSTRACT FROM PUBLISHER]

Extraskeletal osteosarcoma is a very rare tumor in humans and animals including rats. This paper describes a case of extraskeletal osteosarcoma observed in the glandular stomach of an aged female Fischer 344 rat. Grossly, a whitish solid mass was observed at the greater curvature of the glandular stomach. Histologically, the tumor consisted of both atypical polygonal and pleomorphic spindle-shaped cells, with pleomorphic nuclei, and it contained variable amounts of osteoids and small clumps of mature bone tissue. In addition, mitotic figures were frequently observed. Neither invasion of the muscle layer or vessels in the stomach nor metastasis to distant organs was detected. There were no skeletal tumors in the body. Immunohistochemically, the tumor cells were positive for osteocalcin, osteonectin, vimentin and S-100 protein. Judging from these results, the present tumor was diagnosed as extraskeletal osteosarcoma. This is the first report of spontaneous extraskeletal osteosarcoma arising from the stomach in a rat. [ABSTRACT FROM AUTHOR]

A highly invasive intracranial malignant schwannoma containing several masses was detected in a 28-week-old male Crl:CD(SD) rat. Macroscopically, 3 masses were noted in the cranial cavity; one was present at the bottom of the cranial cavity and involved the trigeminal nerve, and the other two were in the parietal bone. Histologically, each mass consisted of fusiform cells with interlacing fascicular, wavy and nuclear pseudopalisading arrangements and round cells with cystic lesions. The tumor cells invaded not only the brain but also the parietal bone. In the brain, the tumor cells infiltrated diffusely into the leptomeningeal and perivascular spaces and parenchyma, in which the tumor cell morphology and invasive pattern closely resembled those of malignant astrocytoma and malignant reticulosis. Immunohistochemically, the tumor cells in the masses showed positive reactions for both S-100 protein and GFAP, while those in the cerebral invasion sites were negative for GFAP and less positive for S-100 protein. Electron microscopically, a single basal lamina layer and short intricate cell processes were confirmed in the tumor cells. From these results, the present tumor was diagnosed as a malignant schwannoma arising in the cranial cavity, probably originating from the trigeminal nerve. The present tumor is considered to be a relatively unique malignant schwannoma based on its growth and invasion patterns. [ABSTRACT FROM AUTHOR]