Treatment of Feline Mammary Fibroepithelial Hyperplasia Following a Single Injection of

Vitásek R. , H. Dendisová: Treatment of Feline Mammary Fibroepithelial Hyperplasia Following a Single Injection of Proligestone. Acta Vet. Brno 2006, 75: 295-297. A case of fibroepithelial hyperplasia of the mammary gland in the cat is reported. A seven-monthold female cat was presented for diffuse enlargement of all of the mammary glands. The cat was treated with proligestone (Covinan®) for the suppression of estrus. Four weeks later all 8 mammary glands were asymmetrically enlarged. There was ulceration of one gland. Sonographic imaging of the affected mammary glands showed homogeneous and granular structures. The patient was treated with subcutaneous injections of 10 mg/kg aglépristone (Alizine®) on days 1, 2, 7, 14 and 21. Within six weeks the mammary glands had completely regressed. No side effects were observed. It is the first case of fully documented feline mammary fibroepithelial hyperplasia and its treatment in the Czech Republic. Queen, progestin, antiprogestin, progesteron Feline mammary fibroepithelial hyperplasia is a growth disturbance of cats characterised by rapid, non-neoplastic proliferation of ductal epithelium and stroma of the mammary gland resulting in enlargement of one, several or all of the mammary glands (Allen 1973). Other terms for the same condition can by found in literature, including feline mammary hypertrophy, feline mammary fibroadenomatosis and fibroadenoma (Nimmo and Plummer 1981). The condition occurs spontaneously in young, sexually intact queens at the time of puberty, during the first oestral cycle, pregnancy or pseudopregnancy and may regress spontaneously or require ovariectomy. Feline mammary fibroepithelial hyperplasia can be induced by administration of progesterone-containing compounds including synthetic progestins such as megestrol acetate and medroxyprogesterone acetate (Hayden et al. 1989; Gorl inger et al. 2002; MacDougal l 2003; Loret t i et al. 2004). In most cases, fibroepithelial hyperplasia can by diagnosed based on typical clinical findings such as diffuse, firm swelling of one or more glands without signs of inflammation (Wehrend et al. 2001). The purpose of the present study is to report the symptoms, history, clinical and ultrasound findings and treatment of a cat that developed mammary fibroepithelial hyperplasia after a single injection of proligestone. Materials and Methods History, examinat ion and therapy A seven-month-old female cat (Maine Coon) was presented with diffuse enlargement of all of the mammary glands. Two months earlier 0.75 ml pro toto proligestone (Covinan®, Intervet) had been used for prevention of oestrus. The owner found out enlargement of all mammary glands four weeks after injection of proligestone. At inspection and palpation, the cat had oedematous and distinct asymmetrical enlargement of all 8 mammary glands, with diameters ranging from 10 to 12 cm (Plate XIII, Fig. 1). There was ulceration of one gland. At clinical examination, body temperature, respiration and heart rates were normal. The cat was lethargic and anorectic. Sonographic imaging of the affected mammary glands showed characteristic homogeneous and granular structures (Plate XIII, Fig. 2). ACTA VET. BRNO 2006, 75: 295–297 Address for correspondence: MVDr. Roman Vitásek, Ph.D. Small Animal Clinic, Unviersity of Veterinary and Pharmaceutical Sciences Palackého 1-3, 612 42 Brno, Czech Republic Phone: + 420 541 562 324 E-mail: vitasekr@vfu.cz http://www.vfu.cz/acta-vet/actavet.htm Differential diagnoses included mammary adenocarcinoma or carcinoma, mammary adenoma, or mammary sarcoma or mastitis. Due to the recent history of progestin administration and the involvement of more than 1 gland, mammary hyperplasia was the most likely diagnosis. Patient was treated with subcutaneous injections of 10 mg/kg aglépristone (Alizine®, Virbac) on days 1, 2, 7, 14 and 21. The length, width and height of glands were measured. We calculated the content of the mammary gland (V = l × w × h).

Feline mammary fibroepithelial hyperplasia is a growth disturbance of cats characterised by rapid, non-neoplastic proliferation of ductal epithelium and stroma of the mammary gland resulting in enlargement of one, several or all of the mammary glands (Allen 1973).Other terms for the same condition can by found in literature, including feline mammary hypertrophy, feline mammary fibroadenomatosis and fibroadenoma (Nimmo and Plummer 1981).
The condition occurs spontaneously in young, sexually intact queens at the time of puberty, during the first oestral cycle, pregnancy or pseudopregnancy and may regress spontaneously or require ovariectomy.Feline mammary fibroepithelial hyperplasia can be induced by administration of progesterone-containing compounds including synthetic progestins such as megestrol acetate and medroxyprogesterone acetate (Hayden et al. 1989;Gorlinger et al. 2002;MacDougall 2003;Loretti et al. 2004).
In most cases, fibroepithelial hyperplasia can by diagnosed based on typical clinical findings such as diffuse, firm swelling of one or more glands without signs of inflammation (Wehrend et al. 2001).
The purpose of the present study is to report the symptoms, history, clinical and ultrasound findings and treatment of a cat that developed mammary fibroepithelial hyperplasia after a single injection of proligestone.

History, examination and therapy
A seven-month-old female cat (Maine Coon) was presented with diffuse enlargement of all of the mammary glands.Two months earlier 0.75 ml pro toto proligestone (Covinan ® , Intervet) had been used for prevention of oestrus.The owner found out enlargement of all mammary glands four weeks after injection of proligestone.At inspection and palpation, the cat had oedematous and distinct asymmetrical enlargement of all 8 mammary glands, with diameters ranging from 10 to 12 cm (Plate XIII, Fig. 1).There was ulceration of one gland.At clinical examination, body temperature, respiration and heart rates were normal.The cat was lethargic and anorectic.Sonographic imaging of the affected mammary glands showed characteristic homogeneous and granular structures (Plate XIII, Fig. 2).Differential diagnoses included mammary adenocarcinoma or carcinoma, mammary adenoma, or mammary sarcoma or mastitis.Due to the recent history of progestin administration and the involvement of more than 1 gland, mammary hyperplasia was the most likely diagnosis.Patient was treated with subcutaneous injections of 10 mg/kg aglépristone (Alizine ® , Virbac) on days 1, 2, 7, 14 and 21.
The length, width and height of glands were measured.We calculated the content of the mammary gland (V = l × w × h).

Results
Starting approximately five days after the first injection, a significant reduction in the size of the mammary tissue was seen (Table 1), accompanied by a change of tissue consistency from rigid to elastic to soft.Within six weeks the mammary glands had completely regressed.No side effects were observed.

Discussion
Immunohistochemistry performed on hyperplastic mammary glands detected progesterone receptors in the nuclei of ductal cells, and growth hormone and insulin-like growth factor-I in the cytoplasm of ductal epithelium with no oestrogen receptors detected (Loretti et al. 2004).
Martín de las Mulas et al. (2000) detected progesterone receptors in epithelial cells or in epithelial and stromal cells, oestrogen receptors were detected in approximately half of the cases.Local production of growth hormone (GH) and insulin-like growth factor enhances the proliferation of the mammary tissue in an autocrine and/or paracrine manner, and mammary epithelial cells are capable of producing GH locally under adequate progesterone stimulus (Van Garderen et al. 1997).Progestin-induced local synthesis of growth hormone and insulin-like growth factor in mammary epithelial cells has been proposed as an additional pathogenic mechanism involved in the development of feline mammary fibroepithelial hyperplasia (M o l et al. 1996).In progestin-treated cats mammary fibroepithelial hyperplasia is associated with local GH expression (M o l et al. 1996).
Due to its progesterone dependency, the hyperplasia can by treated by elimination of the source of progestin.Common therapy of feline mammary fibroepithelial hyperplasia is ovariohysterectomy or mastectomy (Hoffmann and Schuler 2000).Thus, until recently, ovariectomy was considered the treatment of choice, leading to regression of the mammary tissue within three to four weeks.
As an alternative treatment, administration of antiprogestins was introduced by Blendinger et al. (1994).The therapeutic mechanism is based on an antagonism to the action of progesterone at its intracellular receptor (Elger and Chawalisz 1999) and, thus, inhibition of its growth stimulating effect.Feline mammary fibroepithelial hyperplasia was treated with the progesterone antagonist aglepristone by Wehrend et al. (2001), Gorlinger et al. (2002), Meisl et al. (2003), N a k et al. (2004).In cases of fibroepithelial hyperplasia which developed after administration of depot progestin, a repeated or prolonged antiprogestin treatment was required until the effects of exogenous progestins subsided.The mammary glands had regressed to normal within 3 to 11 weeks.In conclusion, the treatment of feline mammary fibroepithelial hyperplasia with antiprogestin has proven to be a valuable, well-tolerated and effective therapy.