A rare case of uterine adenomyosis in a Siamese cat

Abstract

A 12-year-old, female Siamese cat with a long-term history of megestrol acetate treatment for suppression of estrus was presented with vomiting and abdominal pain. Uterine adenomyosis was diagnosed after an ovariohysterectomy.

A 12-year-old, intact female, Siamese cat was presented to the referring veterinarian with a 2-day history of persistent vomiting, inappetence, and abdominal distention. The cat had been seen 2 wk prior for routine vaccinations and was showing estrus behavior at that time. Over the past 10 y, she had been vaccinated yearly and had been treated intermittently with megestrol acetate to suppress estrus. The referring veterinarian performed a complete blood (cell) count (CBC) and serum biochemical profile; results from both test panels showed no significant abnormalities. An in-clinic urinalysis was performed and the urine specific gravity was concentrated beyond the upper limit of the refractometer, and there was 3+ proteinuria. The tentative diagnosis was pyometra; the cat was hospitalized overnight and received lactated Ringer’s solution, IV. The case was then referred to the Small Animal Clinic at the Western College of Veterinary Medicine Teaching Hospital.

On physical examination, a firm, painful mass was detected within the caudoventral part of the abdomen. The cat was afebrile and tachycardic (240 beats/min; normal 160 to 220 beats/min). A superficial mobile mass was present along the ventral aspect of the trachea towards the thoracic inlet. The remaining physical examination revealed no other abnormalities.

Blood samples were submitted for a CBC (Abbott Cell-Dyn 3500R; Abbott Laboratories, St. Laurent, Quebec) and a resting thyroxine hormone level (Immulite; Inter-medico, Markham, Ontario). Results from the CBC were unremarkable, and from her resting T4, they were within the reference interval (45 nmol/L; reference interval, 13 to 50 nmol/L). Radiographs of the abdomen revealed convoluted, fluid-filled tubular structures extending from the pelvis to mid-abdomen; they were interpreted as a distended uterus (Figure 1). Feline uteri are not usually visible on plain radiographs (1). Ultrasonographs of the abdominal cavity further defined the structures as an enlarged uterus, with the left horn measuring approximately 1.5 cm in diameter and the right horn and body measuring approximately 1.0 cm in diameter. The normal uterine outer diameter in a cat varies from 0.39 to 0.70 cm, depending on the stage of the estrus cycle (1). The uterine width is largest in the luteal phase, but it enlarges further with uterine lesions or previous progestin treatment (1). The uterine walls appeared thin, but the lumen was filled with heterogeneous material that did not appear to be fluid. Ultrasonographs also showed 2 cysts (0.9 cm and 0.18 cm) on the left ovary. No other abdominal abnormalities were detected. Urine was collected by cystocentesis and submitted for a complete urinalysis, the results of which were unremarkable. Ultrasonographs showed that the mass in the ventral part of the neck was cystic. Further testing was declined by the owner, and the cyst has since resolved spontaneously.

Figure 1.

Ventrodorsal radiograph showing diffusely enlarged and distended uterine horns (arrows).

The cat became markedly depressed throughout the day, so an exploratory laparotomy was scheduled for later that evening. The cat was premedicated with hydromorphone (Hydromorphone hydrocholoride injection USP 2 mg/mL (generic); Sabex, Boucherville, Quebec), 0.1 mg/kg bodyweight (BW), IM, and anesthesia was induced with propofol (Diprivan; Novopharm, Toronto, Ontario), 6 mg/kg BW, IV, and maintained on 1.0 L/min oxygen and 1.5% isoflourane (Isoflo; Abbott Laboratories, St. Laurent, Quebec).

A ventral midline incision was made through the abdominal wall, whereupon enlarged, firm, nodular uterine horns were immediately visible. The entire length of both uterine horns was affected, as was the uterine body. The left ovary had 2 cystic structures, as detected on ultrasonographs. A routine ovariohysterectomy was performed, though ligatures were placed prior to clamping the uterine body, since the tissue was friable. The uterine vessels were ligated separately from the uterine body, which was then singly ligated at the cervix where, grossly, the tissue was normal. Urine was collected via cystocentesis for bacteriological culture. The uterine stump was wrapped in omentum, the peritoneal cavity was lavaged, and the abdominal wall was closed routinely. Cefazolin (Novopharm, Toronto, Ontario), 22 mg/kg BW, IV, was given prior to the surgery and, thereafter, every 90 min throughout the procedure. The uterine horns and body were opened, examined grossly, fixed in formalin, and submitted for light microscopic examination.

Postoperatively, the cat received cefazolin (Novopharm), 22 mg/kg BW, IV, q12h, hydromorphone (Sabex), 0.05 mg/kg BW, IM, q4h, and meloxicam (Metacam; Boerhringer-Ingelheim, Laval, Quebec), 0.1 mg/kg BW, SC, q24h. She became dysphoric after receiving hydromorphone, so the analgesic was changed to buprenorphine (Buprenex; Reckitt and Colman Pharmaceuticals, Richmond, Virginia, USA), 0.01 mg/kg BW, SC, q6h. The buprenorphine treatment was continued at 0.01 mg/kg BW, SC, q8h for 2 d, and meloxicam (Boerhringer-Ingeheim) was given, 0.1 mg/kg BW, PO, q12h for 5 d, after surgery. The antibiotic was changed the following day to amoxicillin-clavulanic acid (Clavamox; Pfizer Animal Health, Kirkland, Quebec), 62.5 mg, PO, q12h for 10 d, and the cat was discharged 4 d postoperatively. No further health concerns were reported in the 6 mo following discharge.

Histopathologic examination of the uterus revealed diffuse adenomyosis of both horns and the body of the uterus. There was endometrial and myometrial hyperplasia, which obliterated the uterine lumen. The walls were at least twice the normal thickness. In areas where the lumen was not obliterated, it was filled with white, adherent material. Endometrial tissue was found within the myometrium, forming glandular structures (Figure 2). The abnormal endometrial tissue appeared to be functional, and no evidence of malignancy was found. Histopathologic examination of the ovaries showed numerous follicles at various stages of development, numerous corpora lutea, and several cystic structures.

Figure 2.

Photomicrograph of a uterine horn section showing endometrial proliferation and invasion of the myometrium characteristic of uterine adenomyosis (arrows). Hematoxylin and eosin. Bar = 1000 μm.

Adenomyosis is defined as a benign condition where endometrial glands and stroma occur in a disorganized fashion deep within the myometrium (2,3). There is also characteristic myometrial hyperplasia surrounding the adenomatous tissue. Diffuse disease is known as uterine adenomyosis, while isolated foci are termed uterine adenomyomata (2). Uterine adenomyosis is a rare disorder of domestic animals, though it does occur with variable frequency in humans (2,4). Uterine adenomyosis is thought to occur due to endometrial invagination and invasion of the underlying muscular layers, though it may also occur outside the uterus through aberrant development of the Mullerian ducts (2). The pathogenesis is not well understood, though increased estrogen, abnormal musculature, and increased luminal pressure have been implicated (2,4,5). The immune responses in adenomatous uteri are also abnormal (4,5). Adenomyosis may co-occur with leiomyomata, polyps, and adenocarcinoma (2). Endometriosis shares several characteristics with adenomyosis, but in endometriosis, aberrant endometrium is found only outside the uterus and endometriosis occurs only in menstruating species (primates).

In women, the most common clinical signs of uterine adenomyosis are dysmenorrhea and menorrhagia, followed by abdominal and pelvic pain and reproductive difficulties (2). Approximately 35% of women are asymptomatic (2). The rare published veterinary cases have been without clinical signs (6), making this cat unusual in that she was presented for vomiting, inappetence, and abdominal pain. In human cases, as in this feline case, definitive diagnosis prior to surgical removal of the uterus is difficult. An enlarged uterus may be noted on ultrasonographs or radiographs, but magnetic resonance imaging is the preferred diagnostic test in women (7). Light microscopy is required to confirm the diagnosis. Hysterectomy or ovariohysterectomy is often the definitive treatment.

The hormonal profile in women with adenomyosis is atypical. Endometrial glands in adenomyosis express more lutenizing hormone, estrogen, and progesterone receptors than in the normal uterus (2). Adenomyotic glands have also been found to secrete excess estrogen and to have higher than normal estrogen sulphatase and aromatase levels, 2 enzymes that increase conversion of androgens to estrogen and also increase estrogen binding (2). These findings, coupled with the success of anti-estrogenic drugs as treatment, support the theory of excess estrogen being a causal factor. The excess estrogen levels in affected women may arise from excess circulating progestins, which elevate aromatase activity, estrogen receptor concentration, and epidermal growth factors (2,6). Initially, progestins oppose estrogenic effects, hence duration of treatment may be important with respect to disease (8). The prevalence of adenomyosis is unexpectedly high in women receiving chemotherapy with the selective estrogen receptor modulator tamoxifen, which has estrogenic effects (4,7). Since this cat received megestrol acetate frequently throughout her life, the exogenous progestins are suspected to have increased her risk for disease. Increased progesterone from corpora lutea, which were numerous in the ovaries of this cat, could also have increased estrogen levels over time through the same mechanisms as exogenous progestins, and thus have contributed to the adenomyosis (6). It is difficult to determine whether the uterine lesions contributed to abnormal ovarian activity or vice versa.

Adenomyosis is correlated with uterine hyperplasia in women and zoo felids (4,6). Endometrial hyperplasia is a reported sequela to progestin therapy in domestic animals; pyometra and other reproductive problems are also potential risks (1). Munson et al (6) found that zoo felids treated with melegestrol acetate were at a 3.6 times higher risk of endometrial hyperplasia and associated reproductive disease than were untreated cats. Progestin treatment significantly increased uterine coiling, curving, and glandular proliferation beyond the changes that normally occur throughout the estrus cycle (1). Synthetic progestins are commonly used for estrus suppression and estrus cycle control in both domestic and zoological animals, the most common being megestrol acetate, melegestrol acetate, and medroxyprogesterone acetate (9). These compounds block gonadotropin releasing hormone (GnRH) production or release. Common side effects in domestic cats and dogs include endometrial hyperplasia, mammary development, and insulin resistance (6,9). Munson et al (6) also found progestin therapy was associated with hydrometra, mucometra, and endometrial mineralization. Cats appear particularly sensitive to adrenocortical suppression and routine doses can cause hypoadrenocorticism (6,8,9). In this cat, there was no evidence of altered steroid profile or insulin resistance, as indicated by normal electrolyte and glucose parameters. The dose and duration of the megestrol acetate treatment previously prescribed for this cat was unknown. Megestrol acetate is not labeled for use in cats, and treatment regimes are variable. Suggested protocols range from 2.5 to 5.0 mg/cat, PO, q24 h for 3 d, if administration is started during estrus, to 2.5 to 5.0 mg/cat, PO, q24 h for 8 to 10 wk, if it is started in diestrus (8). Treatment with 2.5 mg, PO, once weekly for up to 18 mo is suggested for suppression of estrus if it is started in anestrus (8). Varied protocols also exist for its use in treating many feline dermatological problems.

Medical treatment of adenomyosis in women has met with variable success. Oral contraceptives, progestins, antiprogestins, anti-estrogen antibodies, GnRH analogues, and danazol-impregnated intrauterine devices have all been used, with anti-estrogen antibodies, antiprogestins, such as gestrinone or indomethacin, and danazol having the highest success (7). Danazol is a weak androgenic compound that is suspected to act via inhibition of sex steroid production and is a mainstay in endometriosis therapy (8). Severe cases require partial to complete hysterectomy. In veterinary medicine, where reproductive conservation is often less critical, ovariohysterectomy is the most commonly recommended treatment (6).

Both adenomyosis and the prescribed treatments can adversely affect the ability to conceive. This is of concern in rare zoo felids receiving long-term progestin treatment to suppress estrus, as many of these animals will be bred in the future and are genetically valuable. Munson et al (6) caution against the use of exogenous progestins in potential breeding animals; they recommend early breeding or alternating breeding with progestin therapy to maintain reproductive health.

Uterine adenomyosis has been described rarely in the veterinary literature (10). Uterine disease is much less common in the cat than in the dog (6). Pack (3) described a feline case of uterine adenomyosis, with emphasis on the histological appearance and diagnosis of the disease. As in this case, evaluation found a grossly enlarged uterus, endometrial invasion of the myometrium, and purulent debris. Interestingly, the ovaries of both cats had multiple follicles, corpora lutea, and cysts. Tamada et al (10) described a case where adenomyosis and cystic pyometra co-occurred in a Shiba Inu bitch, and a case of adenomyosis diagnosed following uterine torsion has also been described where the dogs showed clinical signs (11). In both these cases, the clinical signs were assumed to be due to the co-occurring lesions, not adenomyosis. In this respect, this case is unusual in that adenomyosis alone caused clinical signs severe enough to warrant exploration and ovariohysterectomy.

Adenomyosis is an important differential diagnosis for uterine disease in both domestic and zoo animals. Uterine adenomyosis may be misdiagnosed clinically, and suggestive lesions merit full light microscopic examination. The potential link of exogenous hormone therapy and adenomyosis deserves further investigation in both veterinary and human medicine.