Leydig cell tumor

In male Sprague-Dawley rats, there was a dose-related increase in testicular Leydig cell tumors and a slight increase in tubular renal adenocarcinoma at the 600-ppm exposure level after exposure for 104 weeks (Maltoni et al. 1986, 1988). EPA and other groups regard such increases as indicative of a hazard potential unless there are reasons to rule this out. However, other authorities believe testicular tumors are common in rats that are not exposed to toxic substances. 

Carcinogenesis In rats, acarbose treatment resulted in a significant increase in the incidence of renal tumors (adenomas and adenocarcinomas) and benign Leydig cell tumors. Further studies showed that the increased incidence of renal tumors found in the original studies did not occur. 

The vasoconstriction, which is caused by cadmium, may underlie the hypertension observed in experimental animals. Cadmium is also carcinogenic in experimental animals, causing tumors at the site of exposure. Also, Leydig cell tumors occur in the testis of animals after acute doses of cadmium sufficient to cause testicular necrosis. This seems to be an indirect effect due to the reduced level of testosterone in the blood, which follows testicular damage. This causes Leydig cell hyperplasia and tumors to occur. 

The numbers of males with testicular Leydig cell tumors was increased in animals exposed to 5.2 mg/kg/day triphenyltin hydroxide for 104 weeks (16.7% as opposed to 1.7% in the controls). 

In the studies of long-term exposure of rats to both triphenyltin hydroxide and bis(tributyltin)oxide, most of the tumors were found in endocrine glands. In addition to the pituitary adenomas associated with bis(tributyltin)oxide and triphenyltin hydroxide, there was also an increased incidence of pheochromocytomas of the adrenal gland, parathyroid carcinomas and pancreatic adenocarcinomas in animals from at least one sex. Triphenyltin hydroxide was associated with an increased incidence of testicular Leydig cell tumors in male rats at the highest dose. Hepatic tumors were found in male and female mice following 80 weeks of triphenyltin hydroxide administration. 

Samson, M., Peale, F. V. Jr, Frantz, G., Rioux-Leclercq, N., Rajpert-De Meyts, E., and Ferrara, N. (2004). Human endocrine gland-derived vascular endothelial growth factor Expression early in development and in Leydig cell tumors suggests roles in normal and pathological testis angiogenesis. J. Clin. Endocrinol Metab. 89, 4078-4088. 

Mostofi, F.K., and E.B. Price. 1973. Tumours of the testis, Leydig cell tumor. Pp 86-99 in Tumours of the Male Genital System. Reprinted 1987. Fascicle 8, Armed Forces Institute of Pathology. 

Chronic oral carcinogenicity studies of NDMA have been conducted with rats, mice and mink. Tumors at sites other than the liver and testis have not been associated with chronic treatment. Terao et al. (1978) observed a 47% increase in the incidence of testicular Leydig-cell tumors, but no tumors in the liver or other tissues, in rats that were treated with 0.5 mg/kg daily doses of NDMA in the diet for 54 weeks. Increased incidences of liver tumors, but not testicular interstitial cell tumors, occurred in rats that received 0.05 or 0.5 mg/kg/day doses of NDMA in the diet for 96 weeks (Arai et al. 1979). In this study, liver tumor incidences were generally higher in female rats than in male rats. Increased incidences of liver tumors also occurred in rats that were treated with NDMA in the diet for 96 weeks at a dose of 10.0 mg/kg/day (Ito et al. 1982) similar treatment with doses of 0.1 or 1.0 mg/kg/day did not produce increased incidences of liver tumors. It should be noted that Wistar rats were tested in both the Ito et al. (1982) and Arai et al. (1979) studies. The reason for the lack of liver... 

In addition to fiver tumors, many PPARa activators also induce testicular Leydig cell tumors as well as pancreatic acinar cell tiunors in rats but not mice (also known as the tumor triad ). Little progress has been made to refine the proposed modes of action for the pancreatic and testicular rat tumors as detailed in Klaunig et al. (2003). As such, the present chapter will focus on the mode of action of PPARa activator-induced fiver tumors. 

Turek, F. W, and Desjardins, C. (1979). Development of Leydig cell tumors and onset of changes in the reproductive and endocrine systems of aging F344 rats. J Natl Cancer Inst 63, 969-975. 

TESTICULAR SEX CORD TUMORS Leydig Cell Tumor... 

Inhibin A is also a sensitive marker of Sertoli cell differentiation (>90% positive). Sertoli cell tumor including its large cell calcifying variant stains variably positive with antibodies to vimentin, cytokeratin, S-100, synaptophy-sin, chromogranin, and neuron-specific enolase. Cytokeratin immunoreactivity in Sertoli cell tumors is usually stronger than that seen in Leydig cell tumors. Immunoreactivity for FLAP is not seen in Sertoli cell tumors. 

Tubular seminoma, which often mimics Sertoli cell tumor architecturally, can be separated from Sertoli cell tumor by its FLAP immunoreactivity and lack of staining for inhibin and cytokeratins. Like Leydig cell tumors, CD99 can be a useful adjunct in identifying Sertoli cell tumors (Table I6.22). > 403,509,5ii-5i7... 

Billings SD, Roth LM, Ulbright TM. Microcystic Leydig cell tumors mimicking yolk sac tumor a report of four cases. Am J Surg Pathol. 1999 23 546. 

FIGURE 18.28 Endometrioid carcinoma, including its Sertoliform variant, shows diffuse strong staining for epithelial membrane antigen (EMA). Sertoli cell and Sertoli-Leydig cell tumors are EMA negative. 

Immunohistochemical stains are important in the diagnosis of Sertoli-Leydig cell tumors because the various cell types can be difficult to recognize and because other tumor types, especially the Sertoliform variant of endometrioid carcinoma, share some histologic features with Sertoli-Leydig cell tumors. Sertoli cells stain for cytokeratin, which highlights tubules and delineates cords, nests, and sheets of immature Sertoli cells, but they are EMA-negative (Fig. The stromal... 

Heterologous elements are present in about 20% of Sertoli-Leydig cell tumors, and immunostains can help with their identification and classification. Gastrointestinal... 

The uncommon Sertoliform variant of endometrioid carcinoma is generally cytokeratin- and EMA-positive and lacks staining for inhibin or calretinin. Positive staining for inhibin and calretinin and lack of staining for EMA helps to differentiate between a Sertoli-Leydig cell tumor and the Sertoliform variant of endometrioid carcinoma (see Table 18.7).474,545,546,550 Sertoli-... 

Leydig cell tumors with pseudoendometrioid tubules almost invariably contain at least focal areas of more typical Sertoli-Leydig cell tumor morphology, and the pseudoendometrioid tubules show positive staining for inhibin and calretinin, and lack staining for EMA. ... 

They lack the primitive stroma and Leydig cells that are present in Sertoli-Leydig cell tumors. Oxyphilic and lipid-rich variants have been described, and Sertoli cell tumors can contain areas of diffuse growth. Immu-nohistochemistry can help to confirm the diagnosis and to differentiate a Sertoli cell tumor from such differential diagnostic considerations as Sertoliform endometrioid... 

FIGURE 18.38 Sertoli-Leydig cell tumor. This tumor shows focal heterologous hepatic differentiation in which the hepatocytic cells show strong cytoplasmic staining for AFP they also stained with anti-hepatocyte antibody. 

Leydig cell tumors are benign ovarian tumors that frequently secrete sufficient testosterone to cause symptoms that lead to their discovery at a small size. They are... 

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