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During a routine long-term drug safety study, lasting approximately 2'12 yr, male Wistar rats, treated with a prolactin-inhibiting compound, developed an excess of Leydig cell tumors (LCTs). Most tumors were typical for the rat but a small number showed an unusual variation and some appeared malignant. The. variation consisted of glandular and/or tubular structures within the tumor mass which occasionally anastomosed and contained an eosinophilic periodic-acid Schiff(PAS) positive material. In a few of these variants, malignant features such as cellular atypia, capsular, and lymphatic invasion and necrosis were seen. No metastases were detected. Detailed morphological and immunohistochemical investigations were conducted in order to establish the cell of origin of these variants. Glandular/tubular structures were found to stain with varying intensity for vimentin and cytokeratin, but were always negative for B-tubulin. The results indicated that the cell of origin of these LCT variants was indeed the Leydig cell and that glandular and/or tubular structures within LCTs represented a form of Leydig cell metaplasia.

We have studied paraffin-embedded specimens of 17 rat granular cell brain tumors (GCBT) from four long-term drug safety carcinogenicity studies by peroxidase-antiperoxidase (PAP) immunohistochemistry with either polyvalent or monoclonal antibodies against glial fibrillary acidic protein (GFAP), S-100 protein (S-100), Leu-7 epitopes, vimentin (VIM), keratin, desmin, and myelin basic protein. We have found that 9 of the 17 GCBT contained GFAP-positive, S-100-positive, and VIM-positive astrocytes, while GFAP-positive and VIM-positive granular cells were observed in 5 of these 9 tumors. Our findings indicate that astroglial cells are involved in rat GCBT and suggest that an astrocytic origin should be considered for these neoplasms.

Quantitative magnetic resonance imaging (MRI) has been used for the in vivo size determination of subcutaneously implanted Dunning R3327-H tumors in male Copenhagen-Fisher rats (N = 18). Images have been recorded using a multislice spin-echo sequence SE(1000/36) with a resolution of 0.2 x 0.2 mm2 in the imaging plane and a slice thickness of 2 mm. The reliability in the MRI size determination was of the order of 10%. The MRI results were compared with caliper measurements. Five months after tumor implantation nine rats were castrated. Orchiectomy led to a marked and statistically significant reduction in tumor growth rate as determined by both methods of quantification. Qualitative MRI information regarding the tumor morphology was compared with that for histological specimens.

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