Primary neoplastic diseases of the CNS in livestock are rare compared to companion animals. Here we describe the clinical, pathologic, and genetic findings in an adult sheep with a high-grade cerebral astrocytoma. Clinically, apathy, ataxia, bilateral amaurosis, and horizontal resting nystagmus were observed. The signs were suggestive of a space-occupying lesion affecting the vestibular and ascending reticular activating systems. The CSF had high total protein, hypercellularity, and pleocytosis. Macroscopically, a friable, gray-pink, ovoid mass (6 × 3 × 4 cm) was observed within most of the right parietal, occipital, and temporal cerebral subcortical areas, extended into the thalamus, hippocampus, and the cerebral peduncles, and reached the ipsilateral choroid plexus and the lateral ventricles. Histologically, the well-delimited, unencapsulated lesion consisted of proliferating neoplastic spindloid-to-polygonal cells mainly arranged in streams and bundles supported by minimal fibrous stroma, and random areas of coagulative necrosis and hemorrhages without pseudopalisading in the center of the mass. Immunohistochemistry revealed strong immunolabeling of spindle cells for S100, vimentin, and glial fibrillary acidic protein. Immunolabeling for neuron-specific enolase was restricted to trapped neurons
oligodendrocyte transcription factor 2 (OLIG2), pan-cytokeratins, and SOX10 were immunonegative.