Atypical Presentation of Ovarian Remnant Syndrome in a Dog

Introduction

Ovarian remnant syndrome (ORS) is a rare condition of spayed dogs and cats, most often associated with signs of estrus. ORS has been associated with neoplasia in dogs, cats, and women.¹ It has also been associated with abdominal pain in women.² Described in this report is a unique presentation of ORS in a dog that included dysuria, frantic vulvar licking, and abdominal pain without signs of estrus.

Case Report

A 2 yr old spayed female miniature poodle weighing 2.4 kg presented on an emergency basis to the Western College of Veterinary Medicine in Saskatoon, Saskatchewan with a history of intermittent frantic licking at her perineum, dysuria, altered behavior, inappetence, and weight loss. The initial clinical signs noted by the owner included a subtle change in behavior (i.e., the dog was quieter and less active). In addition, she was crying to go outside more frequently, was pollakiuric, and vocalizing as if in pain when picked up. This behavior was followed by intermittent episodes where she would aggressively chase her tail and lick at her perineum. Twice in the previous 6 wk period, the dog had been examined by her regular veterinarian and had been treated for a presumptive urinary tract infection (UTI). She was first treated with amoxicillin^a (22 mg/kg per os [PO] q 12 hr) for 10 days. When the signs persisted, a urine culture was performed but revealed no microbial growth; however, because a UTI was still suspected, amoxicillin trihydrate/clavulanate potassium^b (13 mg/kg PO q 12 hr) was prescribed for an additional 14 days. The owner also reported that the dog’s appetite had declined in the 3 wk prior to presentation to the Western College of Veterinary Medicine. The dog also seemed more anxious and uncomfortable with each passing day, and the owner believed the dog had lost about 10% of her body weight.

The dog was up-to-date on vaccinations and was housed primarily indoors with one other dog. The only other medical problems in the dog’s past were a previous diagnosis of right renal agenesis and a heart murmur diagnosed when she presented for ovariohysterectomy (OHE) at 6 mo of age. At the time of the emergency examination, the dog was bright and alert on physical examination but in thin body condition (body condition score was 2/5). Temperature, pulse, and respiratory rate were within normal limits. An intermittent grade 2/6 systolic heart murmur with the point of maximal intensity at the left base was ausculted, and bilateral grade 2/6 luxating patellas were appreciated. Most significantly, two nonpainful, fluctuant, fluid-filled structures were evident on careful abdominal palpation. The first was in the middle abdominal region and the second, thought to be the urinary bladder, in the caudal abdomen. Her vulva was prominent, but there was no vaginal discharge, erythema, or perivulvar dermatitis, and the owner had not noted any such signs previously. The dog cried, spun, and licked aggressively at her vulva during the physical exam.

A complete blood count was within normal limits. The serum biochemical profile revealed a mild elevation in alanine aminotransferase (113 U/L; reference range, 19–59), γ-glutamyl transferase (14 U/L; reference range, 0–7), and glutamate dehydrogenase (50 U/L; reference range, 0–7), as well as mild hypoglobulinemia (19 g/L; reference range, 23–37). Urinalysis, obtained by cystocentesis, revealed 3+ proteinuria and 4+ hematuria with a 1.021 urine specific gravity. Urine sediment examination revealed 4–6 red blood cells/high-power field and abundant debris. Culture of the urine was negative for aerobic bacterial growth. Pre- and postprandial serum bile acid measurement was performed to investigate the cause of the elevated liver enzymes. Both the preprandial (48 μmol/L; reference range, 0–10 μmol/L) and postprandial bile acids (31 μmol/L; reference range, 0–20 μmol/L) were mildly elevated.

Abdominal radiographs revealed a homogeneous mass in the right middle abdominal quadrant (Figure 1A). Ultrasound of the mass showed an ovoid, thin-walled, cystic structure filled with hypoechoic fluid that measured 53 mm in length and 25–40 mm in width. The caudal pole of the cystic structure abutted the cranial pole of the urinary bladder. Unfortunately, the origin of the cyst could not be determined using ultrasound. The only other significant finding on ultrasound was that the right kidney was absent. The cyst’s more caudal and medial location to the left kidney and generalized thin wall, with a lack of septations, was not consistent with a severely hydronephrotic right kidney. Using Doppler, there were no blood vessels found in close association with the cyst. Vaginal cytology revealed 50% cornified epithelial cells. The remaining cells were mature neutrophils and a mixed population of maturing epithelial cells with occasional extracellular cocci bacteria. During estrus, vaginal cytology should reveal > 90% cornified squamous epithelium.^3,4 Fluid from the cyst was aspirated because its origin could not be determined using ultrasound. The fluid was consistent with a transudate. A urologic origin for the cyst was ruled out by comparing the creatinine concentration of the fluid (643 μmol/L) to the urine creatinine concentration (4009 μmol/L). Culture of the fluid was negative for aerobic bacteria. A computed tomography (CT) scan of the abdomen with IV contrast was performed with the dog under general anesthesia. The contrast CT revealed a large cystic, noncontrast-enhancing structure in the area of the right kidney; however, the origin of the cystic structure still remained undetermined. A large blood vessel coursing dorsal and medial to the cystic structure and bypassing it to supply more caudal abdominal structures was appreciated (Figure 1B). No portion of the cystic structure enhanced with contrast.

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Exploratory celiotomy was performed. The cyst was located in the normal anatomic position of the right kidney. When it was gently retracted toward midline, an enlarged right ovary with multiple follicles dorsal to and attached to the cystic structure was revealed (Figure 1C). The large cystic structure appeared to be a portion of the uterine body based on gross inspection. Serum was collected to measure the estrogen concentration prior to removal of the ovary. Ligatures using 3-0 polydioxanone^c were placed around the pedicle and associated vessels to remove the cystic structure and ovary. Biopsies from the left lateral and left medial liver lobes were also obtained using a 4 mm punch biopsy to further investigate the cause for the elevated liver enzymes and bile acids. Grossly, the liver appeared normal. All samples were submitted in 10% buffered formalin for histopathology. Postoperatively, the dog recovered without incident. Tramadol^d (2 mg/kg PO q 12 hr) and meloxicam suspension^e (0.1 mg/kg PO q 24 hr for 5 days) were administered for postoperative analgesia.

Histopathology revealed that the cystic structure was a portion of the right uterine horn with sections of the right oviduct with an entire right ovary attached (Figure 1C). Examination of the ovary revealed follicles in all stages of development and a large corpus luteum (Figure 2). There was no evidence of neoplasia. The liver biopsies were normal except for mild congestion. The serum estrogen level was elevated at 17,500 ng/L (reference range, < 60–400 ng/L). The histological findings and elevated estrogen concentration were consistent with a dog that was in late estrus at the time of surgery. All the findings were consistent with a diagnosis of ORS with a concurrent cystic uterine remnant. In this case, the dog had experienced fairly silent heats with neither vaginal discharge nor behavioral signs of estrus. No crying or licking behavior was observed in the immediate postoperative period. When the dog presented for a reexamination 2 wk after surgery, she had gained back 125 g in body weight and exhibited no signs of abdominal pain. This supported the suspicion that the cystic uterine remnant was the cause of her abdominal pain syndrome at the time of presentation. The dog continued to do well 13 mo after surgery.

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Discussion

ORS refers to the constellation of clinical signs consistent with estrus and proestrus in a previously spayed female animal.^1,4–7 ORS is most commonly the result of surgical error where there is incomplete removal of ovarian tissue.^1,4,6 This can happen if the ovary is dropped during OHE and revascularization of the free floating remnant occurs, if there is incomplete removal of a portion of the ovary due to clamp placement with a remnant left behind in the broad ligament, or if there is ovarian remnant implantation at a port site when the OHE is performed laparoscopically.^1,6 A less common cause of ORS is the existence of ectopic ovarian tissue not appreciated at the time of OHE. That latter situation is sometimes referred to as supernumerary ovary syndrome.^2,7 Ectopic ovaries have been reported in cats, cows, and women.¹ Typically, the ectopic ovary is small and located within the broad ligament, separated from the normal ovary by connective tissue.¹ This current case is interesting because of the unique presentation of the dog. The presenting complaint and clinical signs were more consistent with signs of ORS seen in women and are atypical for this condition in dogs and cats. Even a very experienced veterinarian may encounter a situation where patient factors (e.g., adhesions associated with previous abdominal surgery, unexpected anatomic variation) or intraoperative complications (e.g., hemorrhage) increase the risk of inadvertent incomplete removal of ovarian and/or uterine tissue.² Deviation from sound surgical principles (e.g., blunt rather than sharp surgical dissection of ovarian adhesions from attached surrounding structures) may also contribute to incomplete removal of ovarian tissue.² Preexisting risk factors and intraoperative conditions have not been reported to be major risk factors contributing to cases of ORS in either cats or dogs; however, it is possible that the abnormal anatomy in this dog did complicate accurate identification of the right ovary at the time of OHE. Other factors, such as surgical experience, breed, or the age of the patient at the time of OHE, have not been shown to be predisposing risk factors for ORS in dogs and cats.¹ A few cases series indicate that ORS has been more commonly associated with incomplete removal of the right ovary.^4,5 The more cranial location and tighter adherence to the body wall of the right ovary may make it more challenging to access and exteriorize during OHE.¹

Animals with ORS usually present for clinical signs related to recurrent estrous cycles.^1,4,6–8 Clinical signs can include vulvar swelling, serosanguineous vaginal discharge, mammary development associated with pseudopregnancy, as well as behaviors associated with estrus (e.g., increased attractiveness to males, increased receptiveness to breeding, lordosis, increased playfulness, and increased teasing behavior).^1,4,6–9 The dog reported herein did not display any signs of estrus according to her owner, but instead presented for signs of abdominal pain similar to what is seen in women with ORS.^2,10 The most prominent clinical sign associated with the ovarian remnant and uterine cyst in this patient was sharp, intermittent abdominal pain leading to yelping, circling, and aggressive frantic licking at her vulva. Pollakiuria and dysuria were also exhibited and led to treatment of presumptive UTIs. Women with ORS eventually develop a pelvic pain syndrome, which is typically associated with the presence of a pelvic ovarian mass.² Pain has not been reported as a clinical sign of ORS in either dogs or cats previously.^1,4,8

The time interval between OHE and the return of estrus signs in patients with ORS can vary between several months and several years in dogs and cats.^1,4,5 The dog in this case did not show signs, according to the owner, until 1.5 yr after her OHE. In the intervening time, it is likely that the remnant ovarian tissue was fully functional and undergoing normal estrus cycling with “silent” heats. In response to the estrus cycles, hydrometra developed within the uterine remnant.¹¹ As the uterine remnant enlarged, it likely compressed other abdominal organs and created a feeling of fullness, suppressing the dog’s appetite and leading to weight loss. Intermittent compression of other organs by the cyst, varying with the degree of intestinal ingesta or intestinal gas production, likely led to the signs of intermittent abdominal pain.¹² The cyst may also have led to delayed gastrointestinal transit time, leading to the mild elevation in the pre- and postprandial bile acids. Other possible causes of elevations in bile acids include a prior hepatic insult, microvascular dysplasia, or a portosystemic shunt. Those other possibilities were discounted because of the lack of support on the hepatic biopsies.

In addition to relying on appropriate clinical signs and physical examination findings, other diagnostic tests that can be used to confirm a suspicion of ORS include vaginal cytology, diagnostic imaging, and hormonal assays to evaluate the reproductive status of the patient.^1,4,5,7 For definitive diagnosis, histologic confirmation of remnant ovarian tissue in a previously spayed patient is required.¹ Vaginal cytology was performed in this case and was not helpful because the population of epithelial cells was too diverse. Hormonal assays have been found to be useful for preoperative confirmation of ORS in some cases, but not in others.¹ A serum estrogen concentration > 20 pg/mL is consistent with active follicular activity, and a serum progesterone concentration > 2 pg/mL is consistent with luteal activity from an ovarian remnant in a previously spayed dog or cat, provided other exogenous or endogenous sources of those hormones have been ruled out.¹ The serum estrogen was 17.5 pg/mL; however, that degree of increase can be seen in dogs with other conditions.⁵ For example, including pituitary-dependent hyperadrenocorticism and adrenal adenocarcinoma have been associated with increased levels of sex hormones (e.g., estradiol), indicating that sex hormones are of limited specificity for ORS.⁵ In addition, sex hormone levels can vary between individuals and have episodic secretion.^1,5 Hormone stimulation tests are a better tool for diagnosing ORS because of the cyclical nature of secretion of most hormones.^1,5 In addition, the episodic secretion of estrogen, like most hormones, means that levels are not persistently elevated during estrus.^1,5 Administration of human chorionic gonadotropin in cats and gonadotropin-releasing hormone in dogs have been used to indirectly stimulate the suspected remnant ovarian tissue to produce estrogen, which can then be measured in cats and dogs.^13,14

Imaging can be helpful as part of the workup to confirm the presence and location of ovarian remnant tissue and to rule out possible adrenal gland neoplasia mimicking ORS by secreting sex hormones. Diagnostic imaging may also be used to look for evidence of possible neoplastic transformation, which is a recognized sequela associated with ORS.^1,15 Abdominal ultrasound is a safe and effective means of looking for evidence of remnant ovarian tissue. It is readily available, and in human patients, ultrasound and CT have been shown to be of equivalent sensitivity for detecting ovarian remnants.² In dogs, ultrasound appears to be a sensitive imaging modality for detection of ovarian remnants.^1,16 Ultrasonographic features of ovarian remnants in dogs include either a simple cyst with acoustic enhancement or cysts with multiple hyperechoic septations, acoustic enhancement with or without echogenic fluid, and the presence of anechoic follicles.¹ However, CT with contrast administration may be more sensitive than ultrasound for imaging a cystic abdominal structure because of its ability to better identify the tissue of origin, to detect the degree of vascularity, and to detect evidence of invasion of adjacent organs or vessels that could impact surgical planning.^2,17 In this case, ultrasound and CT both failed to identify the origin of the cyst prior to exploratory celiotomy. The reasons for that were likely multifactorial. The dog’s abnormal anatomy as well as the small size of her active ovary may have made ultrasonographic imaging more difficult as the ovary was pushed up under the rib cage.

Surgical removal by either laparotomy or laparoscopy is the recommended course of therapy.^1,4,5,7,8 Removal is strongly recommended because retained ovarian tissue can undergo neoplastic transformation.^1,7,15 Removal at a time when the patient has clinical signs of estrus or diestrus is advised because it is easier to identify enlarged ovarian structures (i.e., follicles, corpora lutea) at that point in the cycle.⁷ Surgery is not always straightforward because the reasons for retained ovarian tissue are varied and include incomplete removal of ovarian tissue at OHE, revascularization of free-floating ovarian remnants left behind at OHE, supernumerary ovarian tissue, and scar tissue deposition in humans.^1,2,6,8,14 Identification of active ovarian tissue may improve with prior administration of gonadotropin-releasing hormone, which induces follicle formation.¹⁴ Imaging may also aid identification of remnant tissue and assist with planning its removal.^1,16

Conclusion

Reports of ORS in dogs are infrequent. This case was unique because the dog did not have any of the classic signs associated with ORS but instead presented only for signs of abdominal pain, similar to women with ORS. ORS with an associated remnant uterine cyst should be a differential diagnosis for a cystic mass in the region of either ovary in a previously spayed dog or cat and as a differential diagnosis for dysuria and/or abdominal pain in dogs.