Theriogenology Question of the Month

On the basis of the findings during physical exami- nation and diagnostic imaging, an endometrioma (endo- metrioid cyst) was considered to be the most likely diag- nosis for the mass. Color flow Doppler ultrasonography revealed that there was no blood flow within the mass (Figure 3). Exploratory laparotomy was performed. A 4.5 X 3 X 1.5-cm multinodular, cystic, and hemorrhagic mass was adhered to the uterus, bladder, mesentery , and dor- sal body wall. These attachments were dissected, and the mass was removed and submitted for histologic examina- tion. The uterus appeared grossly normal and was left in situ; however, bilateral ovariectomy was performed. Af- ter surgery , the macaque was treated with buprenorphine (0.01 mg/kg [0.0045 mg/lb], IM, q 12 h for 2 days), car- profen (2 mg/kg [0.91 mg/lb], PO, q 12 h for 7 days), and cefazolin (22 mg/kg [10 mg/lb], IM, q 12 h for 7 days). The macaque recovered from surgery without complica- tions. The laboratory technicians were instructed to sup- plement the diet of the macaque with half of a protein bar daily to help it gain weight and attain a higher BCS. On histologic examination, the mass consisted of a central cavity lined by well-differentiated endometrial glands and stroma with hemorrhage and hemosiderin- laden macrophages (Figure 4) . This appearance was considered to be consistent with an endometrioma. The ovaries were histologically normal.

When discussing reproductive problems of NHPs, it is important to mention anatomic and physiologic differences between primates and other mammals. The reproductive anatomy of rhesus macaques is more simi- lar to that of humans than to that of other mammals. Rhesus macaques have a simplex uterus. Their ovaries are located adjacent to the body of the uterus in a more caudal position within the abdomen (ie, they are not located at the caudal pole of the kidneys), 2,3 compared with their location in other mammals. They also have 20- to 35-day menstrual cycles that end with shedding of the endometrial lining of the uterine wall when there has been no implantation of a fertilized oocyte.2,3 These factors are important contributors for the list of differ - ential diagnoses and the diagnostic tests used to identi- fy masses in the caudal aspect of the abdomen in NHPs. Endometriosis is a naturally occurring condition in macaques, other Old World primates, and humans, and it is the result of ectopic growth of endometrium outside the uterus.2–4 The most common sites reported for endometrio- sis for macaques include the surfaces of the ovaries, intes- tines, spleen, and bladder.5 When this growth consists of a discrete mass lined by hormonally responsive endometrial glands, it is also known as an endometrioma (endometrioid cyst).2,3 During menses, these cystic masses fill with blood, which has resulted in their common name of chocolate cysts.2,3 A solitary cyst was detected in the macaque of the present report. However, it is more common that multiple cysts will be found throughout the peritoneal cavity .2,3 Figure 3—Same color flow Doppler ultrasonographic image as Figure 2. The mass in the caudal aspect of the abdomen of the rhesus macaque is indicated by the long arrow, and the blood flow in surrounding tissues is indicated by the short arrow. Figure 4—Photomicrograph of a representative tissue section ob- tained from the wall of the adherent mass in the caudal aspect of the abdomen of the rhesus macaque in Figures 1, 2, and 3. The mass was surgically resected and did not directly communicate with the uterus. The section consists of multiple, well-differentiated, cystic, and branching endometrial glands with endometrial stroma between the glands. There is hemorrhage within the superficial stroma (arrow) near the lumen of the mass (asterisk). H&E stain; bar = 500 µm. Unauthenticated | Downloaded 06/08/26 04:08 PM UTC JAVMA, Vol 240, No. 2, January 15, 2012 Vet Med Today: Theriogenology Question of the Month 153 Currently , the exact etiopathogenesis of endometriosis is unknown, but it is hypothesized to be induced by retro- grade flow of menstrual blood into the peritoneal cavity .4,5 Evidence has been reported that suggests a genetic compo- nent may play a role in endometriosis in both NHPs and humans.6,7 It is currently believed that this is a complex trait in which multiple genes interact with environmental factors to cause disease.7 Potential risk factors have been identified in NHPs, but results have been conflicting. Risk factors cur- rently identified for the development of endometriosis in NHPs include age (more common in animals > 10 years old), ≥ 1 hysterotomy , exposure to exogenous estradiol, and incidence of the disease in related animals.5,7 Common clinical signs of endometriosis include leth- argy , anorexia, constipation, irregular menses, weight loss, menorrhagia, irregular menstrual cycles, abdominal dis- tention, anemia, dysmenorrhea, and a hunched posture (attributed to pain caused by the condition).2,3,5,8 These clinical signs are more often seen during menses because the ectopic endometrial tissue is responsive to estrogen.2,3 However, NHPs and humans can also have subclinical dis- ease,2–4 as in the macaque reported here. Endometriosis typically is diagnosed in the later stages in NHPs, com- pared with the stage for diagnosis in humans, which is most likely attributable to difficulties in detecting signs (including signs of pain) caused by endometriosis. Fail- ure to diagnose endometriosis early in the course of the condition can lead to major sequelae. Endometrial tissue can invade several other tissues, including the diaphragm, liver, and mesenteric and pelvic lymph nodes. Endome- trial tissue can also form adhesions between organs, in- cluding the ureters, colon, uterus, and urinary bladder.5,8 Therefore, there is the potential for life-threatening organ obstruction.6 Finally , because endometrial cysts are hor- mone-responsive structures, they often fill with blood and increase in size at the time of menses.6 Rupture of these cysts can lead to hemoperitoneum, which can be a life- threatening complication of this disease.2,3 Diagnosis of endometriosis in human medicine can be challenging and usually involves the use of multiple diagnostic modalities. The current criterion-referenced standard for diagnosis of endometriosis in humans is laparoscopic assessment combined with histologic exami- nation of excised lesions.4 However, a thorough physical examination in addition to the use of various diagnostic imaging modalities can aid in attaining a presumptive di- agnosis.4 The most useful diagnostic imaging modalities include magnetic resonance imaging and ultrasonography . Transvaginal, transrectal, and transabdominal approaches for ultrasonography have all been used and provide useful information, including size, consistency (cystic vs a solid structure), and extent (definition of the borders) of a mass.2,3 Additional techniques, such as Doppler ultrasonography (to assess vascularization) and 3-D diagnostic imaging (to evaluate topography and vasculature), have proven beneficial.4 Ultrasound-guided aspiration is another technique that can be performed on masses that appear to be fluid-filled structures. If aspirated fluid is found to be dark brown blood (ie, so-called chocolate fluid), a di- agnosis of an endometrioma can be confirmed.2,3 Ultra- sonography has been useful for the assessment of pelvic masses in NHPs2,3 and, for the macaque of the present re- port, assisted in further defining the nature of the mass. Treatment for endometriosis has 2 main goals. Clinicians should attempt to manage pain and to pre - vent serious abdominal complications. 8 Medical treat - ment is targeted at reducing estrogen concentrations to reduce the estrogen-responsive ectopic endometrial tissue and can include administration of progestins, antiprogestins, gonadotropin-releasing hormone ago - nists, gonadotropin-releasing hormone antagonists, and aromatase inhibitors. 8 The long-term success for medical treatment in NHPs has not been rigorously evaluated. Surgical intervention (ie, ovariectomy) can reduce hormonal influences, but this must be weighed against the purported increased risk of osteoporosis in ovariectomized animals.5 Because endometriosis is of - ten diagnosed at later stages in NHPs, severe adhesions may make it difficult to identify ovarian tissue.5 In these situations, medical treatment may be more prudent. Debulking of the mass may also be warranted to reduce pain. In the macaque of the present report, ovariectomy was combined with removal of the mass because of the possibility of obstruction resulting from multiple organ attachments. Histologic examination was performed on all excised tissues to provide a better assessment of the nature of the mass and to ensure ovarian tissue was completely removed. Outcome Five months after surgery , the macaque was evaluated as part of a routine semiannual physical examination. Observa- tion of the macaque in its cage revealed that it was alert and responsive and that there were typical amounts of urine and feces in the cage. The laboratory technicians reported that the appetite and attitude of the macaque were comparable to those of other healthy macaques housed in the same room. The macaque had not been in menses since the surgery . The macaque was sedated with ketamine hydrochloride (10 mg/kg, IM) to enable the veterinary staff to perform a complete physical examination. The macaque had a BCS of 3 and weighed 8.0 kg. All variables examined were within an- ticipated limits. No masses were detected during abdominal or per rectal palpation.

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