Pathology

• Sertoli cell tumors arise from the sustentacular cells of seminiferous tubules and seminomas arise from the germinal epithelium of seminiferous tubules. Interstitial cell tumors arise from Leydig cells located between seminiferous tubules. All three tumors have relatively distinct appearances grossly, but require histopathology for definitive diagnosis.
• Sertoli cell tumors are firm, lobulated, white-to-gray in appearance, and often characterized as “greasy” on palpation. Seminomas tend to be homogeneous, soft, and occasionally lobulated with an ivory appearance when sectioned. Interstitial cell tumors are soft, expansive, and yellow-to-orange in color when sectioned and often contain cysts with serous or serosanguineous fluid.

Natural behavior

• Most primary testicular tumors in the dog are characterized by local invasion and rarely metastasize. Regional or distant metastasis occurs in fewer than 15% of dogs diagnosed with Sertoli cell tumors or seminomas. Interstitial cell tumors very rarely metastasize. Sites of metastasis may include regional lymph nodes (LNs), eyes, brain, lungs, kidney, spleen, liver, adrenal glands, pancreas, skin, and peritoneum.
• Primary testicular tumors can also cause imbalances in sex hormone levels. Sertoli cell tumors can cause signs of feminization and more than 50% of affected dogs display signs of estrogen overproduction. Seminomas and interstitial cell tumors are rarely associated with feminization. Excess estrogen can cause signs such as bilateral symmetric alopecia, cutaneous hyperpigmentation, epidermal thinning, squamous metaplasia of the prostatic epithelium, gynecomastia, galactorrhea, attraction of other males, preputial atrophy, atrophy of the nonneoplastic testicle, and bone marrow suppression.

History and Clinical Signs

• Most dogs with testicular tumors are asymptomatic and a testicular mass is discovered as an incidental finding. Diagnosis is usually made via palpation of an enlarged testicle or a testicular mass during routine physical examination, abdominal ultrasound, or necropsy. Atrophy of the remaining normal testicle is common. Excess estrogen may cause signs of feminization and is the most common paraneoplastic syndrome associated with canine testicular tumors.
• Common clinical signs include bilateral symmetric alopecia and hyperpigmentation, pendulous prepuce, gynecomastia, galactorrhea, atrophy of the penis, and squamous metaplasia of the prostate. The most deleterious effect of hyperestrogenism is bone marrow suppression.

Diagnosis and Staging

• Physical examination of intact male dogs, and particularly older dogs, should always include palpation of the testicles for masses and/or asymmetry. A thorough rectal examination should be performed to evaluate the prostate gland, regional LNs, and perianal region. In dogs with clinical signs of hormone imbalance (excess estrogen or testosterone), serum testosterone and estradiol-17β can be measured along with testosterone/estradiol ratio.
• Definitive diagnosis is achieved by histopathologic evaluation. Complete staging before surgery is generally recommended. Complete blood count (CBC), chemistry profile, urinalysis, abdominal ultrasound, and three-view thoracic radiographs are also recommended.
• Abdominal ultrasound can aid in identification of undescended testicles in the abdominal cavity or inguinal canal, assessment of regional LNs, assessment of prostatic changes, and evaluation of common sites of metastasis, such as the spleen and liver.
• Castration may be performed before full staging for some cases, with the decision to do full workup after histopathologic evaluation, because it is appropriate therapy for most testicular tumors. Histopathologic diagnosis is generally straightforward.

Treatment and Prognosis

• As most primary canine testicular tumors are characterized by local infiltration with low potential for metastasis, orchiectomy is the treatment of choice and is often curative. Exploratory laparotomy is indicated in cryptorchid dogs. In dogs with signs of hyperestrogenism secondary to the primary tumor, clinical signs typically resolve within 1 to 3 months after castration, unless metastatic lesions provide persistent estrogen release. Recurrence of feminization after castration may be associated with the development of metastasis.
• Dogs with bone marrow hypoplasia secondary to estrogen toxicity require close monitoring for complications requiring medical intervention with blood products and/or antibiotics. These dogs carry a guarded prognosis owing to the high morbidity and mortality associated with neutropenia and hemorrhage. Dogs with aplastic anemia likely warrant a poor prognosis.
• Primary testicular tumors occasionally metastasize to regional LNs and distant sites, and therapy other than surgery may be warranted in these dogs. Cisplatin, actinomycin-D, chlorambucil, mithramycin, and bleomycin have been used; however, too few dogs have been treated and evaluated to formulate any conclusions regarding efficacy. Cisplatin was evaluated in three dogs with aggressive testicular tumors with survival times ranging from 5 months to greater than 31 months.

Cryptorchidism

• Cryptorchidism, a common congenital genital defect in male dogs, is diagnosed if either or both testes are not present in the scrotum at puberty. Testes typically descend into the scrotum by 6 to 16 weeks of age in puppies and before birth in kittens. Late testicular descent and undescended testes are heritable defects. Testicular hormone insulin-like factor 3 is produced by prenatal and postnatal Leydig cells and mediates transabdominal testicular descent from the caudal pole of the kidney to the inguinal canal. This hormone induces growth and differentiation of the gubernaculum from the caudal suspensory ligament. Transabdominal migration of fetal testes is independent of androgen presence, but inguinoscrotal descent is mediated by testosterone. During the inguinoscrotal phase of migration, shortening of gubernaculum and eversion of cremaster muscle occur.
• Cryptorchidism is a predisposing factor for the development of Sertoli tumors and seminomas but does not appear to be a factor in the formation of interstitial cell tumors. The incidence of testicular neoplasia in the cryptorchid dogs was 12.7 per 1000 dog-years at risk, whereas for cryptorchid dogs older than 6 years the incidence increased to 68.1 per 1000 dog-years at risk. Inguinal cryptorchidism may further increase the risk of testicular tumor development compared with abdominal cryptorchidism. In one study, dogs older than 10 years were more likely to develop tumors than dogs younger than 6 years.
• Advancements in treatment include the use of laparoscopic‐assisted cryptorchidectomy. However, future studies that compare laparoscopic‐assisted cryptorchidectomy with the traditional approaches are required for a more conclusive determination of the best method for cryptorchidectomy in dogs.
• Testicular cancer is the second most common tumor in older dogs. Cryptorchid males are up to 13 times more likely to develop testicular cancer than normal dogs. Neutering is the best treatment if tumor develops, sometimes followed by chemotherapy. The only way to prevent this type of cancer from occurring is to neuter the animal as a young dog.

Distinguishing features of the principal testicular tumors