Animal Care Clinic
SERTOLI CELL TUMOR
Hematology & Oncology - Theriogenology
Sertoli cell tumor is a testicular tumor arising from the Sertoli cells located within the seminiferous tubules. These tumors are usually slow growing and noninvasive, although 10 to 20 percent may be malignant. Typically, Sertoli cell tumors are discovered as an incidental finding on a routine physical exam. About 25 percent of dogs with this tumor develop the male feminizing syndrome, from the production of estrogen and estrogen-type hormones. It is the most commonly diagnosed tumor in cryptorchid testes, and these tumors can become large enough to cause abdominal distention and overt clinical signs.
DIAGNOSIS OF SERTOLI CELL TUMOR
ETIOLOGY AND RISK FACTORS
- Causes - The specific cause of Sertoli cell tumor development is unknown, but dogs that are cryptorchid have a 10 times greater risk of developing this type of tumor. It is theorized that increased temperatures within intra-abdominal testes may predispose them to tumor development.
- Feminization associated with Sertoli cell tumors is believed to arise from several different influences. It may be produced from synthesis of estrogen by the tumor, by the conversion of testosterone or its precursors to estradiol, or by changes in the ratio of estrogen: testosterone produced by the testis.
- Risk factors
- Age - The mean age of dogs with testicular tumors is 10.2 years, and such tumors are uncommon in dogs < 6 years of age.
- Breed/genetics - Breeds at greater risk of cryptorchidism (e.g. Weimaraners and Shetland sheepdogs) are more likely to develop a Sertoli cell tumor. Boxers are at increased risk of all testicular tumors regardless of cryptorchidism.
- Sex - This is a testicular tumor and therefore, affects only males.
- Geographic/environmental - No known risk
- Other medical disorders - Cryptorchidism increases the risk of developing any type of testicular tumor.
- Prevention - An excellent preventive measure is early castration
HISTORY AND CLINICAL SIGNS
- Species affected - Dogs
- Presenting signs and historical problems - Most dogs that present with Sertoli cell tumors are not ill, and many tumors are found by palpation during a routine physical examination. Signs include soft or firm swellings in one or both testicles, a single enlarged testicle with or without atrophy of the opposite testicle, generalized scrotal enlargement, or infertility in the breeding stud dog.
- Signs of male feminization include enlargement of the mammary glands, bilaterally symmetrical hair loss, hyperpigmentation of the skin, decreased libido, penile atrophy, a pendulous prepuce, and possible enlargement of the prostate.
- In addition, Sertoli cell tumors can cause severe bone marrow hypoplasia and subsequent pancytopenia resulting in weakness, lethargy, and signs of bleeding diatheses (petechiae, ecchymoses, etc.).
PHYSICAL EXAMINATION FINDINGS
- Attitude - Most affected dogs are normal but some may be lethargic and weak if anemia or pancytopenia is present.
- Body condition - The body condition is usually normal, although some male dogs show a body fat distribution pattern similar to that of female dogs.
- Vital signs - Often unremarkable, but can be severely altered (tachycardia, thready pulses, tachypnea, fever) if anemia and/or pancytopenia are present.
- Mucous membranes - Pale if anemia is present, possible petechiation if thrombocytopenia or pancytopenia is present.
- Hydration status - Most dogs are adequately hydrated.
- Head and neck - Unremarkable
- Eyes - Unremarkable
- Oral cavity - Unremarkable except for mucous membranes changes listed above
- Thorax (cardio-pulmonary) - Unremarkable
- Abdomen (gastrointestinal/urinary) - Cryptorchid testicles that develop Sertoli cell tumors may be palpated as abdominal masses. If torsion of the spermatic cord occurs, the dog will become acutely painful and seriously ill, with all the signs of acute abdominal syndrome.
- Reproductive system - Testicular tumors may develop in one or both testes. It is also possible for more than one type of tumor to be present in the same testis.
- Rectal examination may reveal prostatic enlargement associated with squamous metaplasia of the prostate.
- The clinical signs associated with the feminizing syndrome include gynecomastia and galactorrhea.
- Infertility, decreased libido, a pendulous prepuce, and atrophy of the penis and opposite testicle may also be seen. The affected descended testicle may have soft or firm swellings, and generalized scrotal enlargement may be present.
- Lymph nodes - Unremarkable, unless metastasis has occurred to the sublumbar lymph nodes.
- Integumentary system - Skin changes may have a pattern typical of an endocrine alopecia, with or without increased skin pigmentation. Occasionally, some dogs may be pruritic with a papular eruption. Petechiae, ecchymoses or severe bruising may be noted if pancytopenia exists.
- Neurologic examination - Unremarkable
- Musculoskeletal examination - Unremarkable
- Special examination techniques
- A bone marrow biopsy is indicated to confirm bone marrow abnormalities.
- Plasma estrogen levels may be elevated if the male feminizing syndrome is present, but a normal estrogen level does not preclude the diagnosis.
- Serum inhibin is a specific protein that is produced by the Sertoli cells in the testes. Dogs with Sertoli cell tumors generally have elevated levels of this protein.
- Clinical laboratory tests
- CBC - The CBC is especially useful if a functional Sertoli cell tumor affects the bone marrow. With high circulating estrogen levels, thrombocytopenia and neutrophilia are seen initially. With time, neutropenia develops and is usually followed by anemia. Pancytopenia is the end of result of estrogen-induced bone marrow toxicity.The associated anemia is nonregenerative, so reticulocyte counts are typically low.
- Serum biochemical tests - Often, the biochemical tests are normal. With acute abdomen syndrome multiple abnormalities may be noted. If the tumor has metastasized, liver enzymes may be elevated.
- Urinalysis - The urinalysis may reveal bacteria and elevated numbers of white and red blood cells.
- Coagulation profile - If there is evidence of peripheral bleeding, a clotting profile is recommended. Assays include an activated clotting time, partial thromboplastin time, one-stage prothrombin time and platelet count. Abnormalities in platelet counts are the most common alteration seen; however, all tests may be abnormal if disseminated intravascular coagulopathy (DIC) develops.
- Bone marrow aspirate - Evidence of blood dyscrasias indicate the need to assess the bone marrow via aspiration or core biopsy. The presence of pancytopenia and a paucity of available cells may make evaluation of aspirates difficult. Cytology or histopathology of a core biopsy, or histopathologic examination of a formalinized clot from a bone marrow aspirate may be needed.
- Endocrine assays - There are three forms of circulating estrogens that occur in male dogs: estrone, estradiol and estriol. Most commercial estrogen assays measure only estradiol. Elevated estradiol levels are found in approximately 50 percent of dogs with male feminizing syndrome. Normal estradiol levels do not rule out a femininizing tumor. Because feminization may occur with all three types of testicular tumors, elevated estradiol levels are not specific indicators of a Sertoli cell tumor
- Diagnostic imaging
- Radiographs (thoracic/abdominal) - Abdominal radiographs are useful, particularly if the dog is cryptorchid, in order to search for an abdominal mass or sublumbar lymphadenopathy. If a Sertoli cell tumor is suspected, three views of the thorax are also taken since these tumors have potential for metastasis to the lungs.
- Ultrasound (abdominal) - An abdominal ultrasound is useful to identify a mass within the abdomen. The rest of the abdomen is also examined for metastasis.
- Ultrasound (other) - In non-cryptorchid dogs, generalized scrotal swelling is sometimes present. This may prevent accurate identification of a specific mass. A scrotal ultrasound is very helpful to determine if a tumor is present within a swollen scrotum.
- Cytology (fluid or tissue) - Swabs of the prepuce may be cytologically examined. The preputial swabs of animals under the influence of elevated estrogen levels typically have cells that are cornified. In addition, cytology of an aspirate from an abdominal, inguinal or scrotal mass can also be performed. Fine needle aspirate must be avoided or done very cautiously if a coagulopathy exists.
- Biopsy/histopathology - An excisional biopsy provides a better diagnostic sample than aspiration. Tissue is submitted for histopathology at the time of castration and removal of the mass.
DIAGNOSIS AND PROGNOSIS
- Differential diagnosis
- Diseases with reproductive signs similar to Sertoli cell tumors include the following:
- Interstitial cell tumors
- Testicular torsion
- Spermatocele (sperm granuloma)
- Inguinal scrotal hernia
- If the tumor is located in an abdominal testis and abdominal pain or distention is present, then all other potential causes of acute abdominal pain must be ruled out. Examples are listed below:
- Gastrointestinal tract lesions: ulcerations, perforations, obstructions, intestinal volvulus, pancreatitis, mesenteric thrombosis, etc.
- Prostatic abscessation or infarction
- Liver abscessation, biliary obstruction or rupture
- Necrosis or infarction of other tumors
- Urinary tract lesions: fracture or avulsion of the kidney; ureteral, bladder or urethral obstruction or rupture
- Strangulated umbilical, inguinal, perineal or abdominal wall hernias
- If alopecia is present, rule out other causes of endocrine alopecia:
- Growth hormone disorders
- Alopecia X
- Oral administration of estrogenic compounds
- If blood dyscrasias are present, rule out other causes of nonregenerative anemia, thrombocytopenia, and pancytopenia:
- Anemia of chronic disease
- Anemia related to other endocrine conditions
- Toxins or drugs (including commercial estrogenic compounds) that affect the bone marrow
- Immune-mediated aplastic anemia
- Hematopoietic neoplasia
- Myeloproliferative disorders
- Recommended tests - CBC, biochemical profile, abdominal radiographs and ultrasound, possible coagulation and bone marrow assays, cytology and histopathology.
- Summary of diagnostic criteria - Histopathology confirms the diagnosis of Sertoli cell tumor. CBC and bone marrow biopsy is necessary to confirm the diagnosis of estrogen induced bone marrow hypoplasia.
- Prognosis - Many dogs with Sertoli cell tumors are asymptomatic, and many Sertoli cell tumors behave in a benign fashion. The treatment of these cases is usually effective and carries a good prognosis.
- There is a higher incidence of malignancy in cryptorchid tumors, and these cases have an uncertain prognosis. The prognosis improves if the animal is disease free one year after diagnosis.
- Animals presenting with acute abdominal signs require rapid intervention, with stabilization of their immediate signs and corrective surgery, if they are to survive.
- External signs of feminization slowly recede over several weeks following castration
- Animals with mild hematologic abnormalities may recover, but the prognosis is guarded for animals with pancytopenia. Up to 80 percent of dogs with severe blood dyscrasias succumb despite medical and surgical therapy.
TREATMENT OF SERTOLI CELL TUMOR
The treatment of Sertoli cell tumors depends on the location of the tumor and if there are any associated clinical syndromes. The treatment of each animal must be individualized.
- Surgery - Castration is the treatment of choice for Sertoli cell tumors, either scrotal or cryptorchid. Both testes are removed because of the high incidence of tumors involving both testicles. Scrotal ablation should be considered with removal of large testicular masses.
- Preoperatively, a complete medical work-up is performed and medical therapy is instituted for any hematologic abnormalities (see below).
- Dogs with acute abdomen syndrome are stabilized via the use of appropriate intravenous crystalloid and colloid fluid therapy, correction of electrolyte abnormalities, and administration of analgesics and antibiotics as needed. Treatment for DIC may be indicated. Surgery to remove the abdominal testis is performed once the animal is stable, and intensive post-operative care is then instituted. At the time of surgery a complete evaluation of all internal organs is done to check for evidence of metastasis.
- Medical Therapy - Dogs with bone marrow hypoplasia may be quite ill and require significant medical and nursing care. Therapy for anemia, infection, and potential bleeding problems all need to be addressed.
- Intravenous fluids, broad-spectrum antibiotics and transfusions of blood or blood components may be needed to stabilize the patient prior to the surgical removal of the tumor.
- Anabolic drugs (nandralone decanoate 1m/kg/wk IM; oxymetholone 1 mg/kg PO BID, etc.) may be instituted to help counteract the effects of estrogen.
- Bone marrow stimulating factors may also be used, although their efficacy is uncertain. Erythropoietin (Epogen: 50-100 U/kg SC 2-3 times per week) is used to stimulate the red blood cell formation. Granulocyte colony-stimulating factor (G-CSF, Neupogen: 5 ug/kg/day SC)) may be used to stimulate white blood cell formation.
- Bone marrow improvement may take 3 to 6 weeks, but may not be normal for several months. Unfortunately, most animals with bone marrow involvement do not respond to therapy.
LONG - TERM/HOME THERAPY
- Postoperative care - The incision and scrotum are checked daily for any signs of swelling or discharge. Routine castration usually does not require postoperative antibiotics, but if there is a significant amount of discharge from the incision or swelling, infection may be present and antibiotics are advised. Occasionally, a scrotal hematoma may develop postoperatively. Scrotal hematomas may become quite large and can be painful, but they usually resolve on their own. If skin sutures are used, they are removed in 7 to 10 days.
- Chemotherapy - Chemotherapy may be considered for metastatic disease, but is not routinely used for cryptorchid tumors. Some of the drugs that have been used include cisplatin, cyclophosphamide, vinblastine, and methotrexate. Although partial regression may occur for several months, the long-term prognosis for metastatic Sertoli cell tumor is grave.
- Following excision of benign tumors, signs of feminization usually resolve within 8 weeks. Recheck examinations are recommended for 1 and 2 months post-operatively.
- Animals with bone marrow abnormalities are rechecked more frequently. CBCs and platelet counts are typically measured every 5 to 10 days following surgery until improvement is noted, then at 14- to 21-day intervals until hematologic parameters return to normal.
- Animals with suspected malignant Sertoli cell tumor, but no evidence of metastasis, are re-examined at 3, 6, and 12months. A complete physical examination, CBC, profile, and abdominal and thoracic radiographs are performed. An abdominal ultrasound is performed with any evidence of intra-abdominal disease (e.g., lymphadenopathy, liver enzyme elevation, hematologic changes.)
- Animals treated with chemotherapy are monitored as appropriate for the protocol used.
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