Reproductive Oncology

Chapter 222

Reproductive Oncology

Reproductive tumors in the dog and cat are rare in comparison to other cancers because of the common practice of castration and ovariohysterectomy. However, some reproductive tumors have increased incidences in recent decades. Most reproductive tumors are benign and usually are an incidental finding. Therefore local clinical signs typically are seen in these patients, whereas systemic clinical signs may be present in cases of hormone-producing tumors. Treatments and prognosis vary according to the tumor type and invasiveness; however, through the use of surgery, chemotherapy, and radiation therapy, many types of reproductive tumors can be managed more easily.

Testicular Tumors

Testicular tumors are among the most common malignancies in intact male dogs, whereas they are extremely rare in cats. Most of these tumors are undiagnosed and detected as a primarily incidental finding on either physical exam or abdominal ultrasound. In recent decades according to one study, incidences in intact dogs are increased. The prevalence of testicular tumors in the same study was 27%; interstitial cell tumors and seminomas are the most common, followed by Sertoli cell tumor. Although interstitial cell tumors and seminomas do not exhibit prominent clinical signs, Sertoli cell tumors are more likely to be detected because of the manifestation of obvious symptoms associated with hyperestrogenism. In the last decades, only a limited number of cases have been reported in the cat and included seminomas, interstitial cell tumors, teratomas, and Sertoli cell tumors.

Many dogs present with bilateral tumors and occasionally have more than one tumor type. Intact older dogs and dogs of certain breeds such as boxers, German shepherds, and Afghan hounds present an increased risk for testicular tumors. Cryptorchidism significantly increases the risk for tumor manifestation in the dog, particularly for Sertoli cell tumor and seminomas. Cryptorchidism seems to increase the potential of a malignant testis in cats as well. Although studies in people showed an increased risk of testicular cancer after an exposure to environmental factors such as pesticides and radiation, it has yet to be determined in the dog. A possible association to chemical exposure was assumed in dogs that served in Vietnam.

Testicular tumors can be classified into several categories by tissue of origin, such as germinal epithelium of the seminiferous tubules, sex cord stroma, mixed tumors, and tumors of different origin. Germinal epithelium cells give rise to seminoma, teratoma, embryonal carcinoma, and yolk sac carcinoma. Sertoli cell tumors as well as Leydig cell tumors arise from the sex cord stroma, and a mixed characters group of germ cell and sex-cord stromal tumors. Tumors of different origin, such as adenocarcinomas, sarcomas, and gonadoblastomas, rarely have been reported.

The World Health Organization classification of seminomas in the dog labels the tumor histologic morphology as either intratubular (invasive or noninvasive) or diffuse. Further classification of classical seminoma and spermatocytic seminoma can be done and relates to the origin of the tumor cell. Spermatocytic seminomas originate from well-differentiated mature spermatocytes and therefore present a more benign nature in people. Classical seminomas, on the other hand, originate from undifferentiated gonocytes and therefore have a more malignant course. Immunohistochemistry can further differentiate between the two seminoma types. Classical seminomas typically stain positive to placental alkaline phosphatase and periodic acid stain, whereas spermatocytic seminomas are periodic acid stain negative. A recent study found that the expression of CKIT receptor is a sensitive marker for canine seminomas, whereas OCT 3/4, which is a sensitive marker in human seminomas, did not show the same sensitivity in the dog. The same study suggests that because CD30 was not expressed in seminomas it may be a good marker for distinguishing embryonal carcinoma from seminoma.

Interstitial cell tumors are the least common to metastasize, and seminomas and Sertoli cell tumors rarely metastasize in the dog. Tumors that originate in a cryptorchid testicle show a higher metastatic risk in the dog. The most common sites of metastasis are the sublumbar lymph nodes, but metastasis to any organ is possible, including lungs, spleen, kidneys, skin, and central nervous system. In people, the rate of metastasis is much higher than in the dog, in which the incidence is less than 15%.

A common finding of testicular tumors is a palpable mass on the affected testicle or, in the case of a cryptorchid dog, in the inguinal area. These may be accompanied with atrophy of the scrotum and the other testicle. Systemic clinical signs are not common, and when present, usually are associated with Sertoli cell tumor and hyperestrogenism. Estrogen myelotoxicity may have fatal consequences and should be considered as a potentially life-threatening condition in dogs with testicular tumors. Clinical signs associated with myelotoxicity and pancytopenia may include hemorrhage, petechiation, lethargy, decreased appetite, ataxia, and fever. Other clinical signs associated with hyperestrogenism include feminization, symmetric bilateral alopecia, hyperpigmentation, atrophied scrotum and penis, and metaplasia of the prostate. Although feminization was not reported in cats with testicular tumors, masculine behavior was observed in two cases and in one case was attributed to a potential increase in serum testosterone levels. Testosterone production may result in a perianal hernia in the dog, as well as hyperplasia of the prostate and of the perianal glands.

Although a histologic sample is needed for a definitive diagnosis, a fine-needle aspirate has a relatively high sensitivity and high specificity. Generally, aspirates are performed with ultrasound guidance and typically are reserved for owners who resent castration. A thorough physical exam including rectal palpation should be performed. A complete blood count (CBC) may reveal hematologic abnormalities associated with estrogen myelotoxicity, such as pancytopenia. In addition, plasma levels of estradiol-17β should be measured in dogs with feminization signs. However, clinical signs of feminization may exist in the absence of increased levels of estradiol-17β. Complete staging also should include an abdominal ultrasound and thoracic radiographs.

The majority of dogs present with local disease and the preferred treatment is castration with en bloc scrotal ablation. Prevalence of metastasis in cats is increased; however, the number of reported cases is limited. For dogs with estrogen myelotoxicity, the prognosis is guarded even with intensive supportive treatment of broad-spectrum antibiotics and blood transfusions. Recovery of such an insult to the bone marrow may take several weeks to months. Bleomycin sulfate (Blenoxane) and cisplatin (Platinol-AQ) were reported for the treatment of metastatic disease but had mixed results. Cisplatin typically is administered at a dose of 60 mg/m2 IV over 20 minutes, generally every 3 weeks. However, an intravenous saline diuresis should be performed 4 hours before and 2 hours after the administration of cisplatin at a rate of 20 ml/kg/hr. Although reports on radiation treatment are limited, it proved to be effective in the management of testicular tumors.

Penile and Preputial Tumors

Penile and preputial tumors in dogs are rare and no reports exist in the cat. Multiple forms of skin cancer can affect the prepuce and penis; however, transmissible venereal tumor (dogs only) and squamous cell carcinoma are the most common. Transmissible venereal tumors are more common in younger dogs in tropical climate weather, whereas squamous cell carcinoma is more common in lightly pigmented dogs with history of exposure to solar radiation. Mast cell tumors have been reported on the prepuce and may involve the penis. Other tumors of the prepuce and penis include benign masses such as papilloma, hemangioma, fibroma, and sebaceous adenoma. Malignant tumors include lymphoma, hemangiosarcoma, and fibrosarcoma.

Preputial and penile tumors are usually visible and palpable. Clinical signs may include paraphimosis, pineal prolapse, hematuria, hemorrhagic discharge from the prepuce or penis, and dysuria resulting from obstruction. Diagnosis can be determined with fine-needle aspirates or impression smears. A histologic sample should be obtained for definite diagnosis. Further staging requires a CBC, blood chemistry panel, and urinalysis. Because of the potential metastasis of some of the tumors, such as hemangiosarcoma, mast cell tumor, squamous cell carcinoma, and fibrosarcoma, thoracic radiographs and an abdominal ultrasound are warranted. Although transmissible venereal tumors have a low risk to metastasize, such incidences were reported in up to 15% of the cases in one study and therefore complete staging is recommended.

Surgical excision is the preferred treatment for most penile and preputial tumors, excluding transmissible venereal tumors, that typically show complete response with chemotherapy treatment. The extent of surgery and postsurgical therapy should be determined by the type of tumor.

Vincristine (Oncovin or Vincasar PFS) is a common effective treatment for transmissible venereal tumors administered at a dosage of 0.5 to 0.70 mg/m2 IV once a week. Treatment with doxorubicin hydrochloride (Adriamycin) may be attempted in cases of resistance to vincristine. Transmissible venereal tumors are also sensitive to radiation, and in some cases a cure was reported with a single treatment of 1000 cGy. In one study, the entire cohort of 18 dogs achieved complete remission when 1 to 3 fractions of 1000 cGy were delivered.

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Reproductive Oncology

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