JPC SYSTEMIC PATHOLOGY
Signalment (JPC #2329127): 12-year-old Belgian malinois military working dog
HISTOPATHOLOGIC DESCRIPTION: Testicle and epididymis: Expanding and replacing normal testicular architecture and compressing surrounding seminiferous tubules is an unencapsulated, well demarcated, multilobulated densely cellular neoplasm composed of polygonal cells arranged in tubules, islands and cords which are separated and surrounded by dense bands of fibrous connective tissue. Neoplastic cells are triangular to columnar, have indistinct cell borders, a moderate amount of eosinophilic granular cytoplasm with frequent 5 um clear vacuoles (lipid droplets), a round to oval nucleus with coarse chromatin and up to two distinct nucleoli. Cells frequently palisade perpendicular to the basement membrane. Anisocytosis and anisokaryosis are mild. Mitoses average less than 1 per 40 x HPF. Remaining seminiferous tubules are compressed at the periphery of the testicle and are diffusely atrophied, characterized by irregular undulant basement membranes and lack of developing sperm stages, with only sertoli cells remaining. The epididymis exhibits a similar ductular atrophy with lack of mature sperm stages.
- Testicle: Sertoli cell tumor, Belgian malinois, canine.
- Testicle, seminiferous tubules; epididymis: Atrophy, diffuse, moderate, chronic with aspermatogenesis.
- Rare in all species except the dog and bull
- Increased occurrence with age and in cryptorchid testicles
- Miniature schnauzer dogs with persistent Mullerian duct syndrome are predisposed
- Metastasis is rare; but can go to spermatic cord
- Estrogen secretion occurs in 20-30% of tumors and leads to a hyperestrogenism syndrome that may result in feminization, bone marrow suppression, with accompanying thrombocytopenia, anemia, immunosuppression due to granulocytopenia and squamous metaplasia of the prostate, among other features; estrogen secretion is thought to be associated with larger tumor size
- Inhibin, which is produced by neoplastic sertoli cells, reduces testosterone production through inhibition of trophic pituitary hormone secretions and enhances the feminization syndrome via hyperestrogenism
TYPICAL CLINICAL FINDINGS:
- Feminization to include; attraction to other male dogs, redistribution of adipose tissue, symmetrical alopecia, testicular and penile atrophy, gynecomastia, preputial swelling, perineal hernia.
- Some dogs may develop depression of myelopoiesis: thrombocytopenia, hemorrhage, anemia à due to blood loss or decreased erythropoiesis along with infection, fever, and neutropenia
TYPICAL GROSS FINDINGS:
- Well demarcated, very firm (due to abundance of its fibrous stroma), white, with bulging cut surface; irregularly lobulated by dense bands of connective tissue
- May contain fluid-filled cysts or yellow to tan areas of hemorrhage
- Atrophy of the contralateral testicle common
- Local extension of neoplastic cells into the testicular vein and lymphatics may cause a hydrocele, resulting in massive scrotal swelling
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Arranged in well-formed tubules (intratubular pattern) or in a diffuse pattern
- Neoplastic cells are tall and slender (resembling normal Sertoli cells) with indistinct borders; they often contain lipochrome pigment granules; may palisade along stroma
- Nuclei are round to elongate; mitoses are uncommon
- Dense fibrous stroma that may undergo hyalinization
- Fragmentation or loss of basement membranes correlate with proliferative activity and invasiveness and may be a prognostic indicator
- Sertoli cell tumor: The normally present crystals of Charcot-Bottcher (lamellar protein arrays) do not occur in neoplasm; prominent intercellular gap junctions possibly induced by hormonal activity of tumor; oval nucleus oriented at right angles to the basement membrane and often exhibits a deep indentation; a prominent nucleolus is a constant feature and dense chromatin bodies are often associated with the nucleolus; cytoplasm contains a moderate number of mitochondria, lipid droplets, a small amount of rough endoplasmic reticulum, and plentiful smooth endoplasmic reticulum
ADDITIONAL DIAGNOSTIC TESTS:
- Immunohistochemistry: Reported IHC labeling varies; however, if inhibin and anti- mullerian hormone (AMH) are present, the diagnosis can be made with more confidence; positive for vimentin (same as leydig cells)
- Interstitial cell tumor
Gross: Tan to yellow-orange, discrete, and soft, with areas of hemorrhage
Microscopic: Polygonal cells with abundant finely vacuolated eosinophilic cytoplasm and small round nuclei; prominent lipid accumulations; rare mitoses
Gross: Pale to gray, soft; resemble malignant lymphoma cells; compresses adjacent parenchyma; bulging, lobulated and irregular
Microscopic: Large, uniform, fairly discrete round cells, variable amounts of cytoplasm, large round nuclei, prominent nucleoli; arranged in a diffuse or intratubular pattern; multinucleate cells; lymphocytes; mitoses common; individual cell necrosis
- Mixed germ cell-sex cord stromal tumor
Gross: Gray, white or tan, firm, hemorrhage and necrosis in larger tumors
Microscopic: Admixed neoplastic germ cells and Sertoli cells in tubular structures
Immunohistochemistry: Sertoli cells are NSE and vimentin positive; germ cells are negative for NSE
- Rare in domestic species other than the dog
- Reported in the bull, stallion, ram, cat, boar and rat, bottlenose dolphin with multiple reports of animals having more than one testicular neoplasm
- Seen in newborn and young cattle with epididymal aplasia; thought to be due to altered embryogenesis
- Ano H, Hidak Y, Katamoto H. Evaluation of anti-Müllerian hormone in a dog with a Sertoli cell Vet Derm. 2014;25:142-e41.
- Foster RA. Male reproductive system. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier Inc; 2017:1024, 1211-1212.
- Foster RA. Male genital system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Louis, MO: Elsevier Inc; 2016:494-495.
- Agnew DW, MacLachlan NJ. Tumors of the
- Patnaik AK, Mostofi FK. A clinicopathologic, histologic, and immunohistochemical study of mixed germ cell-stromal tumors of the testis in 16 dogs. Vet Pathol. 1993:(30)287-295
- Ramos-Vara JA, Miller MA. Immunohistochemical evaluation of GATA-4 in canine testicular tumors. Vet Pathol. 2009;46:893-896.