ABSTRACT. The histological characteristics of 9 cases of granular cell tumors (GCTs) observed in B6C3F 1 mice were examined to determine their cellular origin. Seven of the 9 cases were found in the uterus and other 2 cases were in the subcutaneous tissue. Tumor cells had abundant granules in the cytoplasm which were stained with PAS and were resistant to diastase treatment. Ultrastructurally, the granules were identified as lysosomes. The cell surface had cytoplasmic processus showing interdigitation with adjacent cells. A character feature of the tumor cells was the presence of a desmosome-like structure on their cell surface but no basal lamina was demonstrated. Although GCTs have been considered to be derived from Schwann cells on the basis of their ultrastructural features and S-100 proteinimmunopositive findings, the absence of basal lamina in the present cases may raise a controversy as to their origin. KEY WORDS: B6C3F 1 mouse, granular cell tumor.

Morphogenesis of craniopharyngeal derivatives of the neurohypophysis found in 14 Fischer 344 (F344) rats was studied. The incidence of the craniopharyngeal derivatives was 0.17% in male (7 out of 4,200) and 0.16% in female (7 out of 4,450) F344 rats. Neither a sexrelated difference in their incidence nor a strain-related difference in their morphological features was observed. Craniopharyngeal derivatives were composed of aberrant epithelial structures consisting of serous acinar and tubular and fusiform cell structures, and most of these derivatives were associated with Rathke's cleft cysts, which are suggestive of a congenital background. The acinar structures were positive for periodic acid-Schiff reaction and negative for Alcian blue stain. Immunohistochemically, cells forming these structures were positive for cytokeratin, and basal cells of the acinar or tubular structures and some of the fusiform cells showed positive staining for alpha-smooth muscle actin. Electron microscopically, these spindle-shaped basal cells had intracytoplasmic myofilaments with focal density in their cytoplasm, and they were regarded to be myoepithelial cells. These findings strongly indicate that the craniopharyngeal derivatives are not a neoplastic lesion but rather are a developmental aberration derived from the stomatodeum, which is known to be the origin of both nasal and oral epithelial tissues, including the parotid glands, other than Rathke's pouch.

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In a carcinogenicity study, a neuronal tumor in the cranial cavity was observed in a 110-week-old female B6C3F1 mouse. At necropsy, the tumor was seen at the site of the pituitary gland. Histologically, the tumor consisted of well-differentiated ganglion cells, nerve fiber/neuropil-like elements and ganglion-like cells. The tumor was composed mainly of ganglion-like cells, which were arranged in solid sheets interspersed with thin fibrovascular stroma. Nissl substance was detected at the margin in the cytoplasm of well-differentiated ganglion cells, and nerve fibers were identified by the Kluever-Barrera method. Immunohistochemically, the well-differentiated ganglion cells were positive for S-100, neurofilament protein (NF), neuron-specific enolase (NSE), synaptophysin, and chromogranin A. The nerve fiber/neuropil-like elements were positive for S-100, NF, NSE, and glial fibrillary acidic protein (GFAP), and the ganglion-like cells were strongly positive only for NSE and synaptophysin. On the other hand, there were no pituitary cells, such as prolactin-positive or adrenocorticotropic hormone (ACTH)-positive cells in the tumor tissue. Detailed histopathological examination suggested that the tumor might be a ganglioneuroma arising from the trigeminal ganglion. This report provides additional histopathological evidence of peripheral nerve neoplasms in mice.

Focal granulomatous inflammation developed in the livers of five 10-week-old male Sprague-Dawley rats. The characteristic features of this lesion were the presence of foreign body multinucleated giant cells engulfing calcium deposits and site-specific development in a fissure formed in a sub-lobation in the left lobe or interlobar fissure of the medial lobe of the liver. To clarify the pathogenesis of this lesion, rat livers showing abnormal sub-lobation or lobar atrophy, rat livers in an acute dermal toxicity study and guinea pig livers in a skin sensitization test were also examined histologically. Consequently, the present lesion was considered to be a reactive change against calcium that was dystrophically deposited in the area of hepatocellular necrosis due to delayed circulatory disturbance caused by external pressure or extension force. Granulomatous lesions like in the present cases should be differentiated from those caused by evident exogenous pathogens such as chemicals or microorganisms.