Pathology in Practice

Vinicius Soares Carreira Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45221.

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 DVM, DACVP
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Ingeborg Maria Langohr Diagnostic Center for Population and Animal Health, College of Veterinary Medicine, Michigan State University, Lansing, MI 48910.

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 DVM, PhD, DACVP
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Heitor Flavio Ferrari Department of Clinics, Surgery and Animal Reproduction, Faculdade de Medicina Veterinária, Universidade Estadual de São Paulo—Araçatuba, SP 16050-680, Brazil.

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 DVM, MS
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Maria Cecilia Rui Luvizotto Department of Clinics, Surgery and Animal Reproduction, Faculdade de Medicina Veterinária, Universidade Estadual de São Paulo—Araçatuba, SP 16050-680, Brazil.

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History

A 7-year-old sexually intact male mixed-breed dog with a 4-month history of a nonpainful left inguinal mass and bilateral flank alopecia (Figure 1) was examined because of straining to urinate (dysuria).

Figure 1—
Figure 1—

Photographs of the inguinal region (main image) and right flank (inset) of a 7-year-old sexually intact male dog that was examined because of flank alopecia and dysuria. Notice the left inguinal mass, the absence of the left testicle in the scrotum, and the reduced volume of the right testicle (main image). Alopecia was symmetric and extended from the lateral aspects of the thighs to the midlateral aspect of the thorax (inset).

Citation: Journal of the American Veterinary Medical Association 241, 1; 10.2460/javma.241.1.55

Clinical and Gross Findings

On physical examination, the dog had symmetric flank alopecia with mild hyperemia and multifocal crusting and hyperpigmentation. By means of palpation, the inguinal mass was determined to be the left testicle fixed in the inguinal canal. The affected testicle was firm and enlarged (7 × 5 cm), with an irregular, multinodular surface. The contralateral testicle was soft, small (3 × 2 cm), and located within the scrotum. Abdominal ultrasonography revealed no uroliths or other obvious urinary tract outflow obstruction. There was circumferential moderate enlargement of the prostate. Results of a CBC were all within reference ranges. A fine-needle aspirate specimen of the inguinal mass was collected, and the dog was subsequently castrated. Additionally, punch biopsy specimens from alopecic and nonaffected, haired skin (from the left and right flank areas) were collected. Both testicles and all skin biopsy specimens were placed in neutral-buffered 10% formalin for histologic examination.

Formulate differential diagnosis from the history, clinical findings, and Figure 1—then turn page

Cytologic and Histopathologic Findings

Cytologic examination of a fine-needle aspirate specimen obtained from the inguinal mass revealed numerous abundantly macrovacuolated cells palisading along a delicate stroma, with occasional formation of rosette-like structures. The cryptorchid testicle was irregular and enlarged. Histologic examination of sections of the cryptorchid testicle revealed multifocal to confluent, intratubular to coalescing sheets of neoplastic Sertoli cells that had extensively replaced the testicular parenchyma (Figure 2). These cells were tall and oriented perpendicular to the supporting tubular basement membrane. Neoplastic cells had indistinct cell margins, abundant eosinophilic vacuolated cytoplasm, and basally oriented oval nuclei with finely stippled chromatin and inconspicuous nucleoli. There were 6 mitoses/10 hpf (400×). Abundant paucicellular, multifocally hyalinized, fibrous stroma dissected and surrounded the neoplastic tissue. The remaining seminiferous tubules were peripherally displaced and compressed, with variable degrees of atrophic change. Histologic examination of sections of the contralateral descended testicle revealed diffuse atrophy, characterized by diffuse loss of spermatogonia (azoospermia). A section of skin from the flank was also examined histologically; diffuse hair follicle arrest (atrophy), with a predominance of hairless telogen follicles, was evident. There was diffuse mild regular epidermal hyperplasia, with orthokeratotic hyperkeratosis and increased melanin pigment (hyperpigmentation).

Figure 2—
Figure 2—

Photomicrographs of sections of the inguinal mass (undescended left testicle; A through D) and contralateral testicle (E) from the dog in Figure 1. A—The undescended testicle was irregularly enlarged. H&E stain; bar = 0.6 cm. B—Intratubular to coalescing sheets of neoplastic Sertoli cells are present in the undescended testicle. H&E stain; bar = 2 mm. C—In the undescended testicle, the neoplastic tissue (asterisk) has replaced and compressed the adjacent testicular stroma. H&E stain; bar = 2 mm. D—Neoplastic Sertoli cells palisade perpendicularly to the tubular basement membrane. Notice the abundant paucicellular stroma. H&E stain; bar = 50 μm. E—The contralateral testicle has evidence of diffuse atrophy, characterized mainly by the absence of spermatogenesis; similar changes were evident in the compressed remaining testicular parenchyma of the undescended testicle. H&E stain; bar = 100 μm.

Citation: Journal of the American Veterinary Medical Association 241, 1; 10.2460/javma.241.1.55

Morphologic Diagnosis

Benign Sertoli cell tumor (SCT) and compression atrophy of remaining testicular parenchyma of the cryptorchid left testicle and diffuse atrophy of the right testicle; diffuse hair follicle and adnexal atrophy, follicular telogenization, and epidermal hyperplasia, with orthokeratotic hyperkeratosis and hyperpigmentation of haired skin (in alopecic areas).

Comments

Cryptorchidism is the incomplete descent of the testicles, epididymis, and spermatic cord into the scrotum.1 Complications of undescended testicles range from impaired to absent function (spermatogenesis and hormone production) to torsion and neoplasia.2 Primary testicular neoplasms in dogs originate from either the germ cells (seminoma), sex-cord stromal elements (SCT and interstitial Leydig cell tumor), or both (mixed germ cell and stromal cell tumor).1,3 The reported prevalence of testicular neoplasia in aged sexually intact dogs is 16%, and age and testicular ectopia are risk factors for SCTs and seminomas.4 Sertoli cell tumors may develop as unilateral or, less frequently, bilateral neoplasms3 and are the least frequent of the 3 most common primary testicular neoplasms in dogs.2,4 In dogs, development of SCTs in ectopic testicular parenchyma has also been reported.5

Sertoli cells support and assist spermatogenesis both structurally (by having a role in spermatogonia and through blood-testicle barrier formation) and functionally (by providing nutrients and hormones [eg, follicle-stimulating hormone]).2 Neoplastic Sertoli cells may be capable of hormone production. Approximately one-third of sexually intact dogs with SCTs develop so-called hyperestrogenism syndrome (HS).3,6–8 This phenomenon is much less frequently associated with Leydig cell tumors3,8 and is rarely associated with seminomas.8,9 In contrast to what the name implies, not all dogs with the syndrome have detectably high serum estrogen concentration.1 Under normal circumstances, expression of inhibin-α in Sertoli cells is restricted to the testicles of canine embryos10 but is often demonstrable in neoplastic Sertoli cells.1,2 High serum inhibin-α concentration can reduce testosterone production through inhibition of trophic pituitary hormone secretion and may play a synergistic role with estrogen in development of HS.1,2 Ultimately, the precise hormonal contributions to development of the syndrome are not completely understood.1

Hyperestrogenism syndrome, irrespective of cause, is clinically characterized by a variety of genital and extragenital changes. These include alopecia, bone marrow suppression (aplastic pancytopenia), feminization (gynecomastia, galactorrhea, redistribution of body fat, pendulous prepuce, linear preputial erythema, reduced libido, and attractiveness to other male dogs), atrophy of the contralateral testicle (in unilaterally affected dogs), epididymal adenomyosis, prostatomegaly, and squamous metaplasia of the prostatic epithelium.1–3,6–8 Coat changes related to high circulating concentration of estrogen consist of perineal and perigenital alopecia, which progresses to bilateral symmetric alopecia with epidermal and adnexal atrophy, similar to changes associated with endocrinopathies such as Cushing's disease and hypothyroidism.2,3,8 Alopecia can also extend to the skin of the abdomen, thorax, and neck.8 In affected dogs, telogen hair retention may result in lightening of coat color with various degrees of hyperpigmentation and lichenification.8 Estrogen-induced aplastic pancytopenia can result in anemia, leukopenia, and thrombocytopenia, which predispose dogs to secondary infections and hemorrhagic diathesis and may be life-threatening.2,3,7 Metaplastic changes affect the columnar epithelium lining the ducts and glands of the prostate.7 Squamous debris expands and may obstruct the prostatic glandular lumina and urethral lumen at the level of the seminal colliculus.1 Combined with prostatic enlargement, these changes may result in impaired urine flow (dysuria), as likely occurred in the dog of the present report. Hyperestrogenism syndrome is highly associated with but not restricted to SCTs. The presence and severity of these changes are directly related to the volume of the neoplastic mass1,8 and often resolve once the neoplasm has been completely excised.1,3,8 Such changes may also be used to corroborate the diagnosis of SCT.8 Although histologic evaluation of sections of a testicular mass alone is often enough to reach the diagnosis of SCT, results of inhibin-α immunohistochemical analysis may aid in the diagnosis.11

Grossly, SCTs are gray to white, firm, multinodular masses with a lobulated appearance and are clearly demarcated from the surrounding compressed testicular parenchyma.1–3,6,7 Sertoli cell neoplastic tissue exfoliates well, yielding cytologic preparations with moderate to abundant cellularity.12 Microscopic examination reveals that the cells often palisade along fibrovascular stalks with multifocal central circular areas of eosinophilic, periodic acid–Schiff-positive, amorphous material within rosette-like arrangements of Sertoli cells (so-called Call-Exner bodies).12,13 Histopathologic findings for the dog of this report were typical of benign SCT.

Excision of affected testicles and scrotal ablation is often the sole recommended treatment for dogs with localized disease.7,13 Treatment for malignant SCTs consists mainly of surgical extirpation7,14 combined with chemotherapy (eg, cisplatin administration).7,15 In aged sexually intact male dogs, clinical signs related to HS may be the first noted clinical signs that warrant further investigation for an underlying testicular neoplasm. The dog of this report developed symmetric flank alopecia and dysuria as part of a feminization syndrome associated with development of an SCT in a cryptorchid testicle; signs of HS resolved after surgical removal of the tumor, with no subsequent relapse.

References

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