Spontaneous testicular neoplasm in mice with testicular feminization.

Testicular neoplasms occur spontaneously in androgen insensitive mice with testicular feminization (tfm/y); they are composed of Leydig cells, lipid-laden cells, fibroblastlike cells, and macrophages. The small Leydig cells in the periphery of the tumor are structurally similar to nontumorous tfm/y Leydig cells, whereas centrally located large Leydig cells contain numerous lipid droplets, mitochondria with tubular cristae, and abundant smooth endoplasmic reticulum. The lipid-laden cells exhibit a crescentic nucleus which is displaced toward the periphery of the cytoplasm by a large lipid vacuole. The fibroblastlike cells have a large amount of rough endoplasmic reticulum, lysosomes, free ribosomes, and lipid vacuoles. Macrophages are characterized by numerous layered and dense osmiophilic structures closely associated with crystalshaped bodies. An in vitro study shows that, in comparison with the normal testes, the tfm/y tumors produce significantly less testosterone but a larger quantity of androstenedione. Also, the tumors are capable of converting progesterone to estrone and estradiol-17 beta. The plasma level of testosterone is significantly lower in tumor-bearing animals than in normal littermates, but slightly higher than in the nontumorous tfm/y animals. Since the abnormal steroid enzyme activity is found in both tumor-bearing and nontumorous tfm/y mice, the basic cause of aberrations in sex steroid production appears to be genetic rather than the direct result of alterations in their Leydig cells.