Sertolioma in a Canadian Husky: Relationship between Tumor, Hormones, Neurons and Skin

Abstract

Background: Sertolioma is a slow-growing, non-invasive, firm and nodular tumor, malignant in 10% to 22% of cases and with low metastatic potential. Old age and cryptorchidism increase up to 26 times its chances of development and associates it with malignancy. Paraneoplastic syndrome, shown in 20% to 30% of the animals, is due to the aromatization of testosterone or the direct production of estrogen by tumor cells, leading to signs of feminization and bone marrow aplasia. The objective of this article is to report a case of sertolioma in a dog with dermatological characteristic symptoms, but presenting an unusual aggressive behavior, both completely reverted after castration.

Case: A 9-year-old, uncastrated, aggressive and uncontrollable Canadian Husky dog was treated at the Institutional Veterinary Hospital with parapenial volume increase and generalized alopecia. A scrotal testis of reduced size and flaccid consistency and a mass in a parapenial region of 11 x 7.5 x 8 cm in diameter, with a cystic contour, adhered to the abdominal musculature and painless to palpation were detected. Cytology of the parapenial mass presented an image compatible with seminoma or sertolioma, and the preputial smear revealed a predominance of superficial cells. Ultrasound examination showed a heterogeneous inguinal mass, with expansive cystic area, compatible with mass in retained inguinal testis. Therapeutic course consisted of bilateral orchiectomy. Ectopic testis was firm to the cut, had whitish to yellowish coloration and was surrounded by a tunica containing 200 mL of serosanguinolent liquid. The histology of the mass revealed sertolioma-compatible cell characteristics, with cell proliferation circumvented by fibrous connective tissue forming poorly delimited lobes, moderate polymorphism with elongated cells, arranged in a palisade at the periphery of the lobes, vacuolated eosinophilic cytoplasm and vesiculous round nuclei. The unretained testicle revealed signs of atrophy. After surgery the patient showed a progressive improvement of the dermatological symptoms. However, what most caught the attention was the change in aggressive behavior, and fifteen days after surgery the animal was extremely docile and easily restrained during the clinical examination.

Discussion: Hyperesthyrogenism due to sertolioma results from: 1) direct synthesis of estrogen by neoplastic tumor cells 2) increase in metabolism by central conversion (testicular cells) or peripheral hepatocytes, myocytes, adipocytes, hair follicles and neural tissue) androgens into estrogen through the aromatization of testosterone and 3) androgen and estrogen rate imbalance. Testosterone is considered responsible for the aggressive behavior in males, evidenced by the decrease of this behavior when the testicles are removed, and by the reinstallation of this behavior when the hormonal replacement is done. However, research on mice showed that estrogen-sensitive regulatory pathways also play a role in promoting this behavior. Although practically undetectable in male circulation, its presence stems from in vivo synthesis from the aromatization of testosterone, and it is this local estrogen, peripherally synthesized in the brain, that would be responsible for the control of dimorphic behaviors in males. The importance of the estrogen signaling pathway in aggression has also been reported in a study in knockout mice for estrogen receptors, in which males rarely exhibited aggressiveness. Such information is sufficient to support the hypothesis that the disappearance of the aggressiveness of the reported animal was obtained due to castration and correction of hyperestrogenism, showing the importance of including it as an important cause of aggressive behavior in uncastrated male dogs.