عنوان مقاله [English]
Introduction: Hepatoid glands or Perianal glands are modified sebaceous glands in carnivores which they are referred to as, because of their histologic resemblance to hepatocytes (Kokila et al., 2016). In adult male dogs these glands enclose the subcutaneous perianal tissues, but in female dogs these glands creat diffuse islands in the subcutaneous perianal tissues (Wilson et al., 1979). Most hepatoid gland tumors are adenoma type. Carcinomas of these glands are malignant tumors that show more aggressive behavior than adenomas (Jardim et al., 2018). Hepatoid gland tumors are seen in uncastrated males at the age of 8 to 12 years (Wheler et al., 1996). However, lower numbers have also been observed in sterile female dogs and males (Berrocal et al., 1989). The risk of tumors in these glands in males is 5-6 times higher than in females (Atoji et al., 1989). Approximately 10% of these tumors occur ectopically in other locations, such as the tail, perineal area, prepuce, flank, thigh, back, sacra-lumbar region, midline of abdomen, cheek, head and neck (Trangadia et al., 2014). Hepatoid gland tumors are the third most prevalent among canine skin tumors, with reported frequency of benign cases about 58-96% and frequency of malignant cases about 3-17% (Vail et al., 1990; Trangida et al., 2014). Malignant hepatoid gland tumors may metastasize to the sacral and sublumbar lymph nodes. However, the risk of metastasis in these tumors is estimated 10 to 30% (Goldschmidt et al., 2002). Three types of surgery, radiation or chemotherapy are often used to treat tumors in dogs (Doustar et al, 2010). The ectopic incidence of these tumors in regard to their anatomical locations has increased the importance of this report.
Material and methods: In January and March of 2019, two cases of skin tumors observed in two dogs with different breeds in Isfahan Veterinary Pathology Center (private section). First Case: A male terrier dog, 18 years old and weighing 10 kg, kept at home and uncastrated. The reason for the dog's referral was due to the prominent growths on the skin of the flank and the left hand with rapidly growing. At clinical examination, the masses were firm in palpation, painless, and wounded with bleeding, about 4 to 5 cm in diameter in the flank region and about 2 to 3 cm in diameter on the left hand. Second Case: A male German shepherd dog, 10 years old and weighing 35 kg which was kept in a garden around Isfahan. The reason for the referral was also the appearance of a large, rapidly growing, wounded mass in the back of the neck and below the collar, which had a firm stiffness in the palpation. Within a month the mass had reached a diameter of about 15 cm. The animal was febrile and inappetence due to infectious nature of the tumor mass. The animal was also uncastrated. Two cases were biopsied and tissue samples in 10% neutral formalin were sent to Isfahan Veterinary Pathology Center for histopathological examination.
Results and Discussion: In histopathological examination, hepatoid gland with tissue structure similar to normal hepatoid glands was observed. The glandular tissue was divided into separate sections by fine trabeculae of connective tissue. Proliferation of hepatoid cells was observed in the gland tissue. Hepatoid cells observed with distinct border, polyhedral, round to oval with eosinophilic cytoplasm and partly granular with relatively large vesicular nucleus containing one or two prominent nuclei. Also smaller reserve cells were observed sparsely. The stroma included blood capillaries and inflammatory cells. The mitotic figures were prominent and abundant. In addition, congestion and hemorrhage (in the first case) and necrosis and infiltration of inflammatory cells especially neutrophils (in the second case) were also observed. According to histopathological findings, the lesions were diagnosed in both cases as Well Differentiated Hepatoid Gland Carcinoma. Histopathologically, hepatocellular tumors are classified into three groups: adenoma, carcinoma and epithelioma. Berrocal et al. (1989) divided the hepatoid gland tumors into four groups: well-differentiated, moderately or poorly differentiated, carcinomas without differentiation and non-characteristic perianal structures, and reported their frequency, 58.3%, 21.6%, 16.5% and 3.6%, respectively. Well-differentiated carcinomas of the hepatoid glands are similar to hepatoid gland adenomas microscopically. Therefore, careful microscopic examination and observation of hepatoid cell proliferation, reserve cells and presence of mitotic figures may indicate the malignancy of these glands (Goldschmidt et al., 2002). Development of hepatoid gland tumors is hormone-dependent (Atoji et al., 1989). Therefore several studies have been done on androgen receptors in normal and neoplastic hepatoid glands (Yamusak et al., 2016). Hepatoid gland adenomas usually respond positively to estrogen hormone therapy, so that these tumors subside following estrogen administration or castration (Wilson et al., 1979). In the female dogs, most tumors are developed following ovariohysterectomy, decrease of estrogen level and inability to suppress hepatic gland tissue growth, and in the male dogs, interstitial cell tumors lead to the elevated androgen levels in affected dogs, so the rate of hepatoid gland tumors increases (Hayes et al., 1977). However, hepatocellular carcinomas do not subside after treatment with estrogen or castration (Vail et al., 1990). Some have also suggested that dogs with hepatocellular carcinoma benefit from estrogen treatment rather than castration (Pisani et al., 2006). Although surgery is the best treatment, but in addition to surgery and extensive tumor resection, castration and anti-androgen therapy could be used in the treatment of the male dogs (Devi et al., 2012).
Conclusion: At this study none of the affected dogs were castrated. Therefore, as a conclusion, their old age, male sex, sexual activity and probably high androgen levels might be increased the risk of hepatocellular carcinoma in two cases. However, further studies are needed to determining the effects of these hormones on carcinogenesis of these tumors.