Signalment:  

Twenty-three month old male Wistar Transgenic, Rattus norvegicusThis rat was noted to have a swollen testicle on 3/9/2010. Physical examination revealed a quiet but responsive animal with mild ocular porphyrin staining and a swollen discolored scrotum. Only one testicle was found in the scrotum on palpation. The rat was a sentinel animal and was not previously used in research studies. The animal was submitted to necropsy for complete postmortem evaluation on the day after examination.

Gross Description:  

Gross examination revealed pale mottled lungs, an enlarged spleen covered by white material and a mottled liver with a roughened surface. Multiple areas of yellow-brown pigmentation were in the omentum and the mesentery. The right testicle was in the scrotum. The left testicle was in the abdomen. Both testicles were cystic with multiple cysts containing a thick, yellow-tinged fluid.

Histopathologic Description:

The normal architecture of the testicle is effaced by large sheets of neoplastic cells separated by thin septa and multifocal variably sized cystic spaces which contain eosinophilic material with cysts lined by flattened to cuboidal epithelial cells. The neoplastic cells are polyhedral to cuboidal and have acidophilic, often vacuolated, cytoplasm with small round to oval nuclei. At the periphery occasional seminiferous tubules are observed. These tubules are lined by one layer of cuboidal cells and rare giant cells with minimal evidence of normal spermatogenesis. The surface of the tunica vaginalis has multifocal papillary projections which consist of proliferative cuboidal epithelioid cells overlying a fibrovascular core. Similar neoplastic cell proliferation is associated with the tunica vaginalis of the epididymis.

Morphologic Diagnosis:  

1. Interstitial cell tumor, left testicle
2. Mesothelioma, left testicle
3. Diffuse severe testicular atrophy and degeneration with cyst formation

Condition:  

Interstitial cell tumor; mesothelioma

Contributor Comment:  

The incidence and types of primary testicular neoplasms vary between the different stocks and strains of rats. For neoplasms of gonadal stromal origin, interstitial cell (Leydig cell) tumors occur most frequently in older male rats with incident rates approaching 90% in the Fischer 344 (F344) strain(1) and 11% in the Wistar stock(5). Interstitial cell tumors are uncommon in the Sprague-Dawley stock(1). Leydig cells are found adjacent to the seminiferous tubules in the testicle and produce testosterone in the presence of luteinizing hormone (LH). When Leydig cells are stimulated by the pituitary hormone LH, the cells may grow uncontrollably and form a Leydig cell tumor(6). These tumors are usually benign(1), however they may be hormonally active and have been associated with concurrent hypercalcemia(4,6). This neoplasm usually has a nodular growth pattern. In larger neoplasms, testicular architecture may be completely effaced(1). Mesotheliomas are tumors arising from the serosal membranes of the coelomic cavities. The tunica vaginalis propria testis is one of these cavities, which is formed by an outpouching of the abdominal peritoneum. Mesothelioma occurs most frequently in the pleural or peritoneal cavity, but in rare cases these tumors can also arise from the mesothelial cell lining of the tunica vaginalis testis of the testes and epididymis(1). Mesotheliomas are occasionally encountered in laboratory rats with a higher incidence (2.3%) in the F344 strain(3). Spontaneous mesotheliomas have not been reported in the Wistar rat. To the authors knowledge, this is the first reported case of concomitant interstitial cell tumor and mesothelioma in the testicle of a Wistar rat.

JPC Diagnosis:  

1. Testis: Interstitial cell tumor.
2. Testis, vaginal tunics: Mesothelioma.

Conference Comment:  

Interstitial cell tumors, common in rats and rabbits, often exhibit hemorrhage, necrosis, and mineralization; none of which are features of this case. Typically, interstitial cell tumors demonstrate immunoreactivity for inhibin, and mesotheliomas demonstrate immunoreactivity for vimentin and cytokeratin. Ultrastructurally, interstitial cell tumors contain lipid droplets, lipofuscin, abundant smooth endoplasmic reticulum, desmosomes, and characteristic tubulovesicular mitochondrial cristae; whereas, other testicular and epididymal cells have lamellar mitochondrial cristae. Ultrastructural features of mesothelioma include a microvillous cell membrane, junctional complexes, pinocytotic vesicles, and a distinct basal lamina. Microfilaments are often abundant and may be difficult to differentiate from endothelial cells(2).

Conference participants discussed the atrophy of the seminiferous tubules and lack of sperm in the epididymis; likely due to elevated temperature associated with the intrabdominal location.

References:

1. Boorman GA, Everitt, JI. Neoplastic Disease. In M.A. Suckow, S.H. Weisbroth, and C.L.Franklin, eds. The Laboratory Rat 2nd Edition, Amsterdam, Netherlands: Elsevier Academic Press; 2006: 479-511.
2. Percy DH, Barthold SW: In Pathology of Laboratory Rodents and Rabbits Third ed. Blackwell, Ames, IA: 2007:174-177.
3. Goodman DG, Ward JM, Squire RA, Chu KC, Linhart MS: Neoplastic and nonneoplastic lesions in aging F344 rats. Toxicol. Appl. Pharmacol. 48:237-248, 1979.
4. Troyer H, Sowers JR, Babich E: Leydig cell tumor induced hypercalcemia in the Fischer rat. Am. J. Patho. 108:284-290, 1982.
5. Poteracki J, Walsh K.M: Spontaneous Neoplasms in Control Wistar Rats: A Comparison of Reviews. Toxicological Sciences 45:1-8, 1998.
6. Carlson G, Sibley RK. Electron microscopy of testicular and paratesticular neoplasms. In: Russo J, Sommers SC, eds. Tumor Diagnosis by Electron Microscopy. vol. 2, Philadelphia, PA:Field and Wood Medical Publishers, Inc.; 1988:140-153, 159.

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