{"paper_id":"941da686-3bf3-4cb9-8f31-fe1d1a85e390","body_text":"JAVMA, Vol 240, No. 2, January 15, 2012 Vet Med Today: Theriogenology Question of the Month 151\nHistory\nA 14.5-year-old sexually intact female rhesus ma -\ncaque (Macaca mulatta) was evaluated as part of a rou-\ntine semiannual physical examination. This macaque \nwas part of a colony used for pharmacological studies \nand was currently enrolled in such a study .\nThe macaque was housed at a university facility ac-\ncredited by the Association for the Assessment and Accredi-\ntation of Laboratory Animal Care International. It arrived at \nthe facility in 2003, and its medical history and reproduc-\ntive history prior to arrival at the facility were unknown. \nThe macaque had a history of fluctuations in weight (6.7 to \n8.0 kg [14.74 to 17.6 lb]) and BCS (1.5 to 3 [scale of 1 to \n5]1) that appeared to be associated with the time of menses \nas well as a firm uterus that was detected during per rectal \npalpation. Menses had occurred at approximately 30-day \nintervals during the 2 years preceding this semiannual ex-\namination. Duration of hemorrhagic flow during each men-\nses ranged from 1 to 5 days. However, there were 4 months \nin which menses was not detected or perhaps not recorded.\nObservation of the macaque while in its cage re -\nvealed that it was alert and responsive and that there \nwere typical amounts of urine and feces in the cage. The \nmacaque was sedated with ketamine hydrochloride (10 \nmg/kg [4.5 mg/lb], IM) to enable veterinary staff to per-\nform a complete physical examination. \nRectal temperature, respiratory rate, and heart rate \nwere all within reference limits. The macaque had a low \nBCS (1.5) and weighed 6.8 kg (15.0 lb). Six months pre-\nviously , the macaque had weighed 6.7 kg and had the \nsame BCS. Mild periodontal disease was detected, and \nthere was a palpable mass (approx 5 X 4 cm) evident \nin the caudal aspect of the abdomen. No abnormalities \nwere detected during per rectal examination. \nA blood sample was obtained from the right femo-\nral vein. Results of a CBC were within reference limits, \nbut serum biochemical analysis revealed hypophospha-\ntemia (1.5 mg/dL; reference range, 2.4 to 6.5 mg/dL). \nDiagnostic testing was conducted to determine the \ncause of the mass and the hypophosphatemia. The ma-\ncaque was removed from the pharmacological behav -\nioral study in which it was a subject.\nAdditional diagnostic tests were conducted to character-\nize the abdominal mass. Radiographs of the abdomen were ob-\ntained. Contrast was reduced because of a lack of body fat, but an intrapelvic soft tissue opacity was seen during evaluation \nof radiographs. Abdominal ultrasonography was performed to \nfurther characterize the nature of the mass (Figure 1). Color \nflow Doppler ultrasonography was performed (Figure 2).\nQuestion\nWhat are the 3 most likely differential diagnoses for \na cavitated mass in the caudal aspect of the abdomen in \nthis sexually intact rhesus macaque? Please turn the page.\nTheriogenology Question\nof the Month\nIn cooperation with\nThis report was submitted by Katherine A. Shuster, DVM; Jean A. \nNemzek-Hamlin, DVM, MS, DACVS; Nichole K. Baker, BAS; Ingrid \nL. Bergin, VMD, MS, DACLAM, DACVP; and Megan H. Nowland,  \nDVM, DACLAM; from the Unit for Laboratory Animal Medicine \n(Shuster, Nemzek-Hamlin, Bergin, Nowland) and the Department of \nVascular Surgery (Baker), Medical School, University of Michigan, \nAnn Arbor, MI 48109.\nAddress correspondence to Dr. Shuster (shuster1@msu.edu).\nFigure 1—Transabdominal ultrasonographic image of a mass in \nthe caudal aspect of the abdomen detected during a routine semi-\nannual physical examination of a 14.5-year-old rhesus macaque \n(Macaca mulatta). Distance between cursors No. 1 is 1 .7 cm, and \ndistance between cursors No. 2 is 2.2 cm. The bright hyperechoic \nstructure bordering the mass is a section of colon.\nAbbreviations\nBCS Body condition score\nNHP Nonhuman primate\nFigure 2—Color flow Doppler ultrasonographic image of the \nmass in the caudal aspect of the abdomen of the rhesus ma -\ncaque in Figure 1 . \nUnauthenticated | Downloaded 06/08/26 04:08 PM UTC\n\n\n152 Vet Med Today: Theriogenology Question of the Month JAVMA, Vol 240, No. 2, January 15, 2012\nAnswer\nEndometrioma and endometriosis, ovarian cyst, \nand uterine leiomyoma.\nResults\nOn the basis of the findings during physical exami-\nnation and diagnostic imaging, an endometrioma (endo-\nmetrioid cyst) was considered to be the most likely diag-\nnosis for the mass. Color flow Doppler ultrasonography \nrevealed that there was no blood flow within the mass \n(Figure 3). \nExploratory laparotomy was performed. A 4.5 X 3 \nX 1.5-cm multinodular, cystic, and hemorrhagic mass \nwas adhered to the uterus, bladder, mesentery , and dor-\nsal body wall. These attachments were dissected, and the \nmass was removed and submitted for histologic examina-\ntion. The uterus appeared grossly normal and was left in \nsitu; however, bilateral ovariectomy was performed. Af-\nter surgery , the macaque was treated with buprenorphine \n(0.01 mg/kg [0.0045 mg/lb], IM, q 12 h for 2 days), car-\nprofen (2 mg/kg [0.91 mg/lb], PO, q 12 h for 7 days), and \ncefazolin (22 mg/kg [10 mg/lb], IM, q 12 h for 7 days). \nThe macaque recovered from surgery without complica-\ntions. The laboratory technicians were instructed to sup-\nplement the diet of the macaque with half of a protein bar \ndaily to help it gain weight and attain a higher BCS.\nOn histologic examination, the mass consisted of a \ncentral cavity lined by well-differentiated endometrial \nglands and stroma with hemorrhage and hemosiderin-\nladen macrophages (Figure 4) . This appearance was \nconsidered to be consistent with an endometrioma. The \novaries were histologically normal.\nDiscussion\nWhen discussing reproductive problems of NHPs, \nit is important to mention anatomic and physiologic \ndifferences between primates and other mammals. The \nreproductive anatomy of rhesus macaques is more simi-\nlar to that of humans than to that of other mammals. \nRhesus macaques have a simplex uterus. Their ovaries \nare located adjacent to the body of the uterus in a more \ncaudal position within the abdomen (ie, they are not \nlocated at the caudal pole of the kidneys), 2,3 compared \nwith their location in other mammals. They also have \n20- to 35-day menstrual cycles that end with shedding \nof the endometrial lining of the uterine wall when there \nhas been no implantation of a fertilized oocyte.2,3 These \nfactors are important contributors for the list of differ -\nential diagnoses and the diagnostic tests used to identi-\nfy masses in the caudal aspect of the abdomen in NHPs.\nEndometriosis is a naturally occurring condition in \nmacaques, other Old World primates, and humans, and it \nis the result of ectopic growth of endometrium outside the \nuterus.2–4 The most common sites reported for endometrio-\nsis for macaques include the surfaces of the ovaries, intes-\ntines, spleen, and bladder.5 When this growth consists of a \ndiscrete mass lined by hormonally responsive endometrial \nglands, it is also known as an endometrioma (endometrioid \ncyst).2,3 During menses, these cystic masses fill with blood, \nwhich has resulted in their common name of chocolate \ncysts.2,3 A solitary cyst was detected in the macaque of the \npresent report. However, it is more common that multiple \ncysts will be found throughout the peritoneal cavity .2,3\nFigure 3—Same color flow Doppler ultrasonographic image as \nFigure 2. The mass in the caudal aspect of the abdomen of the \nrhesus macaque is indicated by the long arrow, and the blood \nflow in surrounding tissues is indicated by the short arrow.\nFigure 4—Photomicrograph of a representative tissue section ob-\ntained from the wall of the adherent mass in the caudal aspect of the \nabdomen of the rhesus macaque in Figures 1, 2, and 3. The mass \nwas surgically resected and did not directly communicate with the \nuterus. The section consists of multiple, well-differentiated, cystic, \nand branching endometrial glands with endometrial stroma between \nthe glands. There is hemorrhage within the superficial stroma (arrow) \nnear the lumen of the mass (asterisk). H&E stain; bar = 500 µm.\nUnauthenticated | Downloaded 06/08/26 04:08 PM UTC\n\n\nJAVMA, Vol 240, No. 2, January 15, 2012 Vet Med Today: Theriogenology Question of the Month 153\nCurrently , the exact etiopathogenesis of endometriosis \nis unknown, but it is hypothesized to be induced by retro-\ngrade flow of menstrual blood into the peritoneal cavity .4,5 \nEvidence has been reported that suggests a genetic compo-\nnent may play a role in endometriosis in both NHPs and \nhumans.6,7 It is currently believed that this is a complex trait \nin which multiple genes interact with environmental factors \nto cause disease.7 Potential risk factors have been identified \nin NHPs, but results have been conflicting. Risk factors cur-\nrently identified for the development of endometriosis in \nNHPs include age (more common in animals > 10 years \nold), ≥ 1 hysterotomy , exposure to exogenous estradiol, and \nincidence of the disease in related animals.5,7\nCommon clinical signs of endometriosis include leth-\nargy , anorexia, constipation, irregular menses, weight loss, \nmenorrhagia, irregular menstrual cycles, abdominal dis-\ntention, anemia, dysmenorrhea, and a hunched posture \n(attributed to pain caused by the condition).2,3,5,8 These \nclinical signs are more often seen during menses because \nthe ectopic endometrial tissue is responsive to estrogen.2,3 \nHowever, NHPs and humans can also have subclinical dis-\nease,2–4 as in the macaque reported here. Endometriosis \ntypically is diagnosed in the later stages in NHPs, com-\npared with the stage for diagnosis in humans, which is \nmost likely attributable to difficulties in detecting signs \n(including signs of pain) caused by endometriosis. Fail-\nure to diagnose endometriosis early in the course of the \ncondition can lead to major sequelae. Endometrial tissue \ncan invade several other tissues, including the diaphragm, \nliver, and mesenteric and pelvic lymph nodes. Endome-\ntrial tissue can also form adhesions between organs, in-\ncluding the ureters, colon, uterus, and urinary bladder.5,8 \nTherefore, there is the potential for life-threatening organ \nobstruction.6 Finally , because endometrial cysts are hor-\nmone-responsive structures, they often fill with blood and \nincrease in size at the time of menses.6 Rupture of these \ncysts can lead to hemoperitoneum, which can be a life-\nthreatening complication of this disease.2,3\nDiagnosis of endometriosis in human medicine can \nbe challenging and usually involves the use of multiple \ndiagnostic modalities. The current criterion-referenced \nstandard for diagnosis of endometriosis in humans is \nlaparoscopic assessment combined with histologic exami-\nnation of excised lesions.4 However, a thorough physical \nexamination in addition to the use of various diagnostic \nimaging modalities can aid in attaining a presumptive di-\nagnosis.4 The most useful diagnostic imaging modalities \ninclude magnetic resonance imaging and ultrasonography . \nTransvaginal, transrectal, and transabdominal approaches \nfor ultrasonography have all been used and provide useful \ninformation, including size, consistency (cystic vs a solid \nstructure), and extent (definition of the borders) of a mass.2,3 \nAdditional techniques, such as Doppler ultrasonography \n(to assess vascularization) and 3-D diagnostic imaging \n(to evaluate topography and vasculature), have proven \nbeneficial.4 Ultrasound-guided aspiration is another \ntechnique that can be performed on masses that appear \nto be fluid-filled structures. If aspirated fluid is found to \nbe dark brown blood (ie, so-called chocolate fluid), a di-\nagnosis of an endometrioma can be confirmed.2,3 Ultra-\nsonography has been useful for the assessment of pelvic \nmasses in NHPs2,3 and, for the macaque of the present re-\nport, assisted in further defining the nature of the mass. \nTreatment for endometriosis has 2 main goals. \nClinicians should attempt to manage pain and to pre -\nvent serious abdominal complications. 8 Medical treat -\nment is targeted at reducing estrogen concentrations \nto reduce the estrogen-responsive ectopic endometrial \ntissue and can include administration of progestins, \nantiprogestins, gonadotropin-releasing hormone ago -\nnists, gonadotropin-releasing hormone antagonists, \nand aromatase inhibitors. 8 The long-term success for \nmedical treatment in NHPs has not been rigorously \nevaluated. Surgical intervention (ie, ovariectomy) can \nreduce hormonal influences, but this must be weighed \nagainst the purported increased risk of osteoporosis in \novariectomized animals.5 Because endometriosis is of -\nten diagnosed at later stages in NHPs, severe adhesions \nmay make it difficult to identify ovarian tissue.5 In these \nsituations, medical treatment may be more prudent. \nDebulking of the mass may also be warranted to reduce \npain. In the macaque of the present report, ovariectomy \nwas combined with removal of the mass because of the \npossibility of obstruction resulting from multiple organ \nattachments. Histologic examination was performed \non all excised tissues to provide a better assessment of \nthe nature of the mass and to ensure ovarian tissue was \ncompletely removed.\nOutcome\nFive months after surgery , the macaque was evaluated as \npart of a routine semiannual physical examination. Observa-\ntion of the macaque in its cage revealed that it was alert and \nresponsive and that there were typical amounts of urine and \nfeces in the cage. The laboratory technicians reported that \nthe appetite and attitude of the macaque were comparable to \nthose of other healthy macaques housed in the same room. \nThe macaque had not been in menses since the surgery . \nThe macaque was sedated with ketamine hydrochloride \n(10 mg/kg, IM) to enable the veterinary staff to perform a \ncomplete physical examination. The macaque had a BCS of 3 \nand weighed 8.0 kg. All variables examined were within an-\nticipated limits. No masses were detected during abdominal \nor per rectal palpation. \nReferences\n1. Clingerman KJ, Summers L. Development of a body condition \nscoring system for nonhuman primates using Macaca mulatta as \na model. Lab Anim 2005;34:31–36.\n2. Tarantal AF . Ultrasound imaging in rhesus ( Macaca mulatta ) \nand long-tailed ( Macaca fascicularis ) macaques: reproductive \nand research applications. In: Wolfe-Coote S, ed. The laboratory \nprimate. San Diego: Elsevier Academic Press, 2005;318–323.\n3. Godfrey LR. General anatomy . In: Wolfe-Coote S, ed. The labora-\ntory primate. San Diego: Elsevier Academic Press, 2005;38–42.\n4. Spaczynski RZ, Duleba AJ. Diagnosis of endometriosis. Semin \nReprod Med 2003;21:193–208.\n5. Mattison JA, Ottinger MA, Powell D, et al. Endometriosis: clini-\ncal monitoring and treatment procedures in rhesus monkeys.  \nJ Med Primatol 2007;36:391–398.\n6. Kennedy S. The genetics of endometriosis. Eur J Obstet Gynecol \nReprod Biol 1999;82:129–133.\n7. Zondervan KT, Weeks DE, Colman R, et al. Familial aggregation \nof endometriosis in a large pedigree of rhesus macaques. Hum \nReprod 2004;19:448–455.\n8. Fanton JW , Hubbard GB, Wood DH. Endometriosis: clinical \nand pathologic findings in 70 rhesus monkeys. Am J V et Res \n1986;47:1537–1541.\nUnauthenticated | Downloaded 06/08/26 04:08 PM UTC","source_license":"CC0","license_restricted":false}