Testicular malignancies

Sarcoidosis may rarely involve the female and male reproductive tracts (234). Sarcoidosis may affect any portion of the female genitourinary tract including the ovary (235), fallopian tube (236), utems (237), and vulva (238). Cases of sarcoidosis of the male testis are particularly problematic because of the concern for possible testicular malignancy. Elevated beta-human chorionic gonadotrophic (p-HCG) and alpha-fetoprotein (AFP) levels are elevated in approximately half of the patients with nonseminomatous testicular carcinoma (239). However, normal levels of these proteins do not exclude the diagnosis of cancer. In an attempt to avoid unnecessary orchiectomy, young males with known sarcoidosis or a clinical situation compatible with sarcoidosis and normal AFP and p-HCG levels could be considered for close observation and repeated ultrasound, a brief empiric trial of corticosteroids, or possibly an excisional biopsy (234). 

Laboratory studies with mice and rats have conclusively demonstrated that the injection of cadmium metal or salts causes malignancies (sarcoma) at the site of injection and testicular tumors. However, the simultaneous administration of zinc is protective against sarcoma and interstitial cell tumor development (USEPA 1980). In rats, no dose-related increases in tumors were found at maximum oral daily doses of 4.4 mg Cd/kg BW (USPHS 1993). Among humans, the available epidemiological evidence is not sufficient to conclude that cadmium is definitely implicated as a carcinogen (USEPA 1980 Nomiyama 1982), although cadmium exposure is associated with lung cancer in humans (Shimada et al. 1998). 

Testicular interstitial cell tumors occur spontaneously in aged rats, and the incidence can vary greatly in control groups. This tumor is believed to be hormonally mediated. There was no evidence of malignancy in three rat studies and no evidence of this type of tumor in mice. It can be concluded that the tumorigenic effect, if real, is most unlikely to be relevant to human exposure [13]. 

Although there was an increased incidence of testicular Leydig cell adenomas in male rats administered 50,000 ppm for 104 wk (Collins et al. 1995), these tumors do not progress to malignancy (Boorman et al. 1990) and have little significance in humans (Cook et al. 1999). The lack of genotoxicity also supports the conclusion that there is no carcinogenic risk for humans. 

Carcinogenesis Animal studies have shown that sirolimus caused an increase in malignant lymphoma and testicular adenoma. 

Dactinomycin is used in curative combined treatment of Wilms tumor, Ewing s sarcoma, rhabdomyosarcoma, and gestational choriocarcinoma. It is active in testicular tumors, lymphomas, melanomas, and sarcomas, although its use in most of these malignancies has been supplanted by other agents. 

Plicamycin (mithramycin, Mithracin) is one of the chro-momycin group of antibiotics produced by Streptomyces tanashiensis. Plicamycin binds to DNA and inhibits transcription. It also inhibits resorption of bone by osteoblasts, thus lowering serum calcium levels. Very little is known about its distribution, metabolism, and excretion. Because of its severe toxicity, plicamycin has limited clinical utility. The major indication for plicamycin therapy is in the treatment of life-threatening hypercalcemia associated with malignancy. Plicamycin also can be used in the palliative therapy of metastatic testicular carcinoma when all other known active drugs have failed. 

In recent RT-PCR studies, many kallikreins have been proposed as new biomarkers for malignancies other than prostate cancer. Breast, ovarian, and testicular cancers are the most studied. Certain kallikreins were found to be differentially expressed in various malignancies (up- or downregulated), and the increase or decrease of their expression may be associated with prognosis [43, 58, 70, 89-94]. We have immunohistochemically evaluated some kallikreins in malignant diseases, including two series of prostate and renal cell carcinoma, and have examined their prognostic values [84, 85]. 

With the identification and characterization of all members of the kallikrein gene family, accumulating evidence indicates that other kallikreins might be also related to hormonal (e.g., breast, prostate, testicular, and ovarian cancers) and other malignancies. KLK6 and KLK10 were originally isolated by differential display from breast cancer libraries [216],... 

Breast, prostate, testicular, and ovarian cancers are all considered hormonal malignancies. Sex hormones are known to affect the initiation or progression of these malignancies. However, all kallikreins are under sex steroid hormonal regulation. Taken together, kallikreins may represent downstream targets by which hormones affect the initiation or progression of such tumors. 

Luo LY, Rajpert-De Meyts ER, Jung K, Diamandis EP. Expression of the normal epithelial cell-specific 1 (NES1 KLK10) candidate tumour suppressor gene in normal and malignant testicular tissue. Br J Cancer 2001 85 220-224. 

Serio G, Ceppi M, Fonte A, et al. 1992. Malignant mesothelioma ofthe testicular tunica vaginalis. Eur Urol 21(2) 174-176. 

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