JPC SYSTEMIC PATHOLOGY
Signalment (JPC #1357631): A dog
HISTORY: Not provided
HISTOPATHOLOGIC DESCRIPTION: Testicle: Two neoplasms are present. First, markedly expanding the testicle and compressing the adjacent seminiferous tubules is an 8 mm diameter, well-circumscribed, encapsulated, multilobulated, densely-cellular neoplasm composed of polygonal cells (interstitial cells) arranged in cords and vague nests supported by a fine fibrovascular stroma. Neoplastic cells have fairly distinct cell borders, moderate amounts of eosinophilic granular or occasionally vacuolated cytoplasm with eosinophilic globules, and one round, central nucleus with finely-stippled chromatin and a prominent magenta nucleolus. There is moderate anisocytosis and anisokaryosis. The mitotic rate is less than 1 per 10 HPF. Rare intranuclear cytoplasmic invaginations are observed. Filling the lumen and replacing spermatogenic and Sertoli cells in approximately 30% of surrounding seminiferous tubules is a second neoplasm composed of round cells (germ cells) with distinct cell borders, scant to moderate amounts of eosinophilic granular cytoplasm, and large, round, vesiculate nuclei with coarse chromatin and 1-2 large prominent magenta nucleoli. There is moderate anisocytosis and anisokaryosis with rare giant cells and frequent multinucleated cells with up to 7 nuclei. The mitotic rate averages 2 per HPF, and there is scattered single cell necrosis. Remaining non-neoplastic seminiferous tubules exhibit degeneration, characterized by irregular undulant basement membranes, decreased to absent spermatogenesis, and occasional spermatid multinuclear giant cells within lumina.
- Testicle: Interstitial cell tumor, breed unspecified dog, canine.
- Testicle: Seminoma, intratubular, multifocal.
- Testicle, seminiferous tubules: Germ cell atrophy, diffuse, moderate, chronic with aspermatogenesis.
- Major categories of primary testicular tumors:
- Germ cell: Seminoma, teratoma, embryonal carcinoma, yolk sac carcinoma
- Sex-cord stromal: Sertoli cell/sustentacular cell, Leydig cell/interstitial cell
- Mixed germ cell-sex cord stromal tumor (seminoma/sertoli - rare)
- Lining epithelium of modified mesothelium: Mesothelioma (rare in most species)
- Others (rare): Rete adenoma and adenocarcinoma, mesenchymal tumors
- Interstitial cell tumor: most common testicular neoplasm of the dog, cat, rat, and bull (Guernsey), reported in boar and stallion (cryptorchid)
- Distinction between hyperplasia and neoplasia is arbitrarily based on size (neoplasms >2mm in diameter) and encroachment on adjacent tissue
- Unilateral or bilateral, single or multiple
- Seminoma: Most common testicular neoplasm in the stallion; second most common in the dog; reported in the ram, goat, bull, and cat
- Unilateral or bilateral, single or multiple; more common in right testicle than left
- Initially begins as the intratubular form which is confined to the seminiferous tubules; later develops into the diffuse form with cells forming broad sheets
- Distinction between benign and malignant is difficult; all should be considered potentially malignant; metastasis rare in the dog, more likely in the horse
- Interstitial cell tumor:
- Often incidental; majority are benign, metastasis is extremely rare
- Cryptorchidism predisposes to genesis of interstitial cell tumors in stallions and possibly cats, but not in dogs
- Most do not produce testosterone
- Metastasis rare despite malignant histologic appearance
- Microvessel density and vascular endothelial growth factor (VEGF) may be useful prognostic indicators for intrinsic malignancy and growth potential
- Cryptorchid dogs have a higher risk of developing seminoma (or Sertoli cell tumor) than those with scrotal testes
- Seminoma more common in inguinal cryptorchid testes
- Sertoli cell tumor more common in abdominal cryptorchid testes
- Contralateral testis (even if scrotal) also at increased risk for neoplasia
- Retained testes, especially if enlarged by neoplasia, are more prone to torsion
TYPICAL CLINICAL FINDINGS:
- Scrotal enlargement, inguinal or abdominal mass
- Interstitial cell tumor (dogs): Commonly associated with perianal gland neoplasia, tail gland and prostatic hyperplasia; rarely causes signs of hyperestrogenism (e.g. gynecomastia, prostatic squamous metaplasia, bone marrow aplasia)
- Seminoma: Pain secondary to hemorrhage and necrosis
TYPICAL GROSS FINDINGS:
- Interstitial cell tumor:
- Yellow, soft, often contains areas of hemorrhage
- Small, round, well circumscribed; cause little distortion of the affected testicle
- Bulge on cut section, frequently cystic or hemorrhagic
- White, soft, bulge on cut section
- Lobulated, irregular, compresses adjacent parenchyma, fine septa, soft
- Bulging, gray, white, or pink, and occasional brown mottling (“fish flesh”)
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Interstitial cell tumor: Resemble normal interstitial cells; round to polygonal, abundant eosinophilic finely granular to vacuolated cytoplasm, often containing prominent lipid accumulations or yellow or brown lipochrome pigment; small round dark nuclei, rare mitoses; PAS-positive intranuclear cytoplasmic invaginations (in up to 15% of cells in canine interstitial cell tumors); three main patterns (>1 pattern may be present in a single tumor):
- Solid-diffuse: Large sheets of uniform cells, fine fibrovascular stroma, palisading around vessels with antibasilar nuclei
- Pseudoadenomatous: Poorly organized lobules surrounding fluid filled spaces; lobules divided by capillaries and small venules
- Cystic-vascular: Interconnecting cords 2-4 cells thick, surround lakes of eosinophilic fluid and erythrocytes; large vascular endothelial lined spaces are often present
- Seminoma: Large, uniform, round cells, discrete cell borders, scant cytoplasm, large round to ovoid nuclei, occasional giant nuclei and multinucleated cells, mitoses common, necrosis and hemorrhage, lymphoid aggregates (CD8+); two main patterns:
- Intratubular: Cells are restricted to the tubules, multifocal
- Diffuse: With progression, intratubular seminomas invade the interstitium and form broad sheets (or less often, cords or lobules); individual cell necrosis and vacuolated histiocytes (“starry-sky” appearance)
- Interstitial cell tumor: Abundant mitochondria with tubular cristae, smooth endoplasmic reticulum; intranuclear cytoplasmic invaginations are composed of smooth and rough endoplasmic reticulum, vesicles and lipid vacuoles, myelin figures, and disrupted membranous profiles
- Seminoma: Straight cell borders not limited by a basement membrane; intercellular bridges; oval nucleus; distinct Golgi complex
ADDITIONAL DIAGNOSTIC TESTS:
- Interstitial cell tumor: Positive for GATA-4, Melan A , inhibin, PLAP (placental alkaline phosphatase), KIT (CD 117) and 3β-HSD (hydroxysteroid dehydrogenase); negative for neuron specific enolase (dogs; one case in a cat was positive for NSE), p53 and p21.
- Seminoma: Positive for vimentin (perinuclear), p53 and p21; negative for GATA-4, inhibin, PLAP, KIT (CD 117), 3β-HSD, and Melan A
- Sertoli cell tumor: Common in the older dog; usually unilateral and associated with cryptorchid testicles; often hormonally active; may exhibit hyperestrogenism (feminization, gynecomastia, atrophy of contralateral testicle, squamous metaplasia of prostate gland, alopecia, bone marrow atrophy); very firm, multinodular, white to grey; consist of variably sized aggregates of Sertoli cells separated by an abundant fibrous tissue stroma; IHC panel similar to interstitial cell tumor but negative for NSE
- Teratoma: Most common testicular neoplasm in young horses; tumor consisting of tissues from more than one germ layer; rare in the dog; unilateral or bilateral, single or multiple; may have both solid and cystic areas and may contain foci of cartilage, bone, fat, or haired skin; histologic appearance is highly variable and depends on the type of tissues produced
- Mixed germ cell-sex-cord stromal tumor: tubules and cords of admixed sertoli cells and germ cells in varying proportions, different than a collision tumor when a seminoma collides with a Sertoli cell tumor
- Embryonal carcinoma: Rare testicular neoplasm derived from poorly differentiated embryonal epithelium; histologically resembles a poorly differentiated carcinoma that may include solid, papillary, or tubular areas embedded in abundant fibrous connective tissue stroma
- Mesothelioma: Derived from the mesothelial lining of the vaginal tunics; form irregular papillary proliferations over the testicular tunics
- Testicular cyst: Derived from remnants of the ducts and embryonic structures associated with sexual development; may occur adjacent to the testicle, epididymis or spermatic cord; cysts are lined by a single layer of epithelium
- Interstitial cell tumor:
- Most common testicular tumor in rats; seen mostly in older F344 rats
- Associated with concurrent hypercalcemia
- Two cell types: polyhedral to elongate cells with granular to vacuolated cytoplasm, and smaller cells with hyperchromatic nuclei and scant cytoplasm
- Third most common testicular tumor in rats (after interstitial cell tumor and mononuclear cell leukemia)
- Seen particularly in F344 strain rats
- Most common primary site is tunica vaginalis of testes with serosal implantation in peritoneal and pleural cavities
- Other important testicular lesions in rats: scrotal hemorrhage and peritesticular/testicular necrosis and fibrinous exudate associated with Kilham’s rat virus (parvovirus); associated with rat parvovirus; polyarteritis nodosa in pampiniform plexus
- Interstitial cell tumor:
- Seminoma is most common testicular neoplasm
- Teratoma is the most common testicular neoplasm in young horses
- Interstitial cell tumor:
- Occurs almost exclusively in cryptorchid testes
- Associated with vicious behavior
- Two cell types: hypertrophic interstitial cell and pleomorphic fusiform cell
- Bull: Guernsey bulls overrepresented and those with interstitial cell tumors have high incidence of hepatic telangiectasis, thyroid C cell tumors, and infertility; neoplastic interstitial cells are not vacuolated and contain little lipid
- Rabbit: Interstitial cell tumor is most common; recent report of testicular granular cell tumor (differential diagnosis for interstitial cell tumor, differentiate by presence of many secondary lysosomes on TEM)
- Cat: Testicular tumors are rare. Interstitial cell tumors can be extratesticular in the scrotal skin and spermatic cord of neutered males. Some of these cats develop male behaviors such as urine marking and male odors
- Human: Interstitial cell tumors are rare and contain Reinke crystals (cytoplasmic inclusions) that are considered diagnostic; seminomas are common, often malignant
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