OVARIECTOMY DUE TO A DERMOID CYST IN AN ORANGUTAN (PONGO PYGMAEUS) Author(s): Zoltan S. Gyimesi, D.V.M., James W. Forrester, M.D., David L. Doering, M.D., Roy B. Burns, D.V.M., and Rita McManamon, D.V.M. Source: Journal of Zoo and Wildlife Medicine, 46(1):167-170. Published By: American Association of Zoo Veterinarians DOI: http://dx.doi.org/10.1638/2014-0176R.1 URL: http://www.bioone.org/doi/full/10.1638/2014-0176R.1

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Journal of Zoo and Wildlife Medicine 46(1): 167–170, 2015 Copyright 2015 by American Association of Zoo Veterinarians

OVARIECTOMY DUE TO A DERMOID CYST IN AN ORANGUTAN (PONGO PYGMAEUS) Zoltan S. Gyimesi, D.V.M., James W. Forrester, M.D., David L. Doering, M.D., Roy B. Burns, D.V.M., and Rita McManamon, D.V.M.

Abstract: A large abdominal mass was identified during an elective preventative health examination in a 25-yrold female hybrid orangutan (Pongo pygmaeus). Sonographically, the mass was fluid-filled and a presumptive diagnosis of a dermoid cyst or cystic teratoma of an ovary was made. Exploratory laparotomy, after assembly of a surgical team, confirmed that the 2.5-kg cystic mass was associated with the left ovary. Following ovariectomy, perioperative dissection of the mass revealed hair components, confirming the working diagnosis. Because the right ovary was slightly nodular and firmer than expected, and these germ cell tumors sometimes occur bilaterally, excision of the contralateral ovary was elected. Histopathology confirmed the left ovarian mass was a dermoid cyst; the right ovary contained a corpus hemorrhagicum but no evidence of neoplasia. Recovery was uneventful and the orangutan was prescribed hormone replacement therapy to mitigate potential problems associated with a chronic lack of estrogen and progesterone. This case report demonstrates the importance of elective examinations under anesthesia, even in well-trained great apes. Key words: Dermoid cyst, germ cell tumor, laparotomy, orangutan, ovariectomy, Pongo pygmaeus.

BRIEF COMMUNICATION A 25-yr-old female hybrid orangutan (Pongo pygmaeus) weighing 52.3 kg was anesthetized for an elective preventative health examination in May 2013. This animal had not been anesthetized for 17 yr, in part due to it being conditioned to allow for a wide variety of medical procedures via operant conditioning (i.e., cursory physical and dental examination, blood and urine collection). The orangutan was premedicated with ondansetron (Natco Pharma Limited, Kothur, 509 228, India; 0.15 mg/kg p.o.) and midazolam (Hospira, Inc., Lake Forest, Illinois 60045, USA; 1.0 mg/kg p.o.) and was induced with tiletamine-zolazepam (Telazolt, Fort Dodge Veterinaria, S.A., 17813, Vall de Bianya (Girona), Spain; 1.9 mg/kg i.m.) and ketamine (KetathesiaTM, Bioniche Teoranta Inverin Co., Galway, Ireland; 1.9 mg/kg i.m.). The orangutan received a dose of glycopyrrolate (West-Ward, Eatontown, New Jersey 07724, USA; 0.01 mg/kg i.m.) and was then intubated with an 11-mm endotracheal tube and maintained

From the Louisville Zoological Garden, 1100 Trevilian Way, Louisville, Kentucky 40213, USA (Gyimesi, Burns); Partners in Women’s Health, 3940 Dupont Circle, Louisville, Kentucky 40207, USA (Forrester); the Norton Cancer Institute, 3991 Dutchmans Lane, 4th Floor, Louisville, Kentucky 40207, USA (Doering); and the UGA Zoo and Exotic Animal Pathology Service, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602, USA (McManamon). Correspondence should be directed to Dr. Gyimesi ([email protected]).

on isoflurane gas anesthesia (IsothesiaTM, Butler Animal Health Supply, Dublin, Ohio 43017, USA; 1.0–3.0%). A large, mobile, abdominal mass was identified by palpation in the central abdomen, just left of midline. A ventrodorsal abdominal radiograph revealed no evidence of mineralization within the mass. Transabdominal ultrasound revealed the mass was a 16.2 3 12.8 3 12.3-cm cystic structure containing fluid with multiple bright echos. A smaller, 7.1 3 5.4 3 5.2-cm hyperechoic mass was identified within the cyst. The uterus appeared sonographically normal and neither ovary could be definitively identified. Based on the appearance of the abdominal mass, a dermoid cyst or cystic teratoma of an ovary was suspected. Anesthetic recovery was uneventful following antagonism with flumazenil (West-Ward; 0.01 mg/kg i.v.). This orangutan had been sterilized via laparoscopic tubal ligation in 1994 and, per staff observations, was sexually active and continued to exhibit reproductive cyclicity. The mass did not appear to be causing any discomfort, yet surgical exploration and removal were elected due to the potential for complications. A surgical team was assembled and 3 mo later the orangutan was scheduled for exploratory laparotomy. In case we encountered adhesions and an enterotomy became necessary, the surgeon requested that on the morning of the day prior to surgery, the orangutan be medicated with an overthe-counter, magnesium citrate laxative (Good-

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Figure 1. Dermoid cyst, associated with the left ovary, in a 25-yr-old hybrid orangutan. The neoplasm measured 18 3 17 3 13 cm and weighed 2.5 kg. Within the fluid-filled cyst were two oblong spongy structures, the larger of which was sparsely covered with hair (arrows).

Sense, Geiss, Destin & Dunn, Inc., Peachtree City, Georgia, USA; 295 ml p.o.) along with a liquid-only diet in an attempt to empty the gastrointestinal tract. Despite good compliance, the orangutan did not defecate the day prior to surgery and had only passed a small amount of normal feces by the following morning. On the morning of surgery, the orangutan was premedicated as before, induced with tiletaminezolazepam (1.9 mg/kg i.m.) supplemented with glycopyrrolate (0.008 mg/kg i.m.), intubated, and maintained on isoflurane gas (0.5–4.0%). Rectal examination revealed normal feces in the rectum; an enema was not administered. The orangutan was positioned in dorsal recumbency and the abdomen was clipped. An intravenous catheter was placed in a cephalic vein for delivery of ceftriaxone (Wockhardt Limited, Mumbai, India; 38 mg/kg i.v.) and for crystalloid fluid support. An indwelling urinary catheter was placed to keep the bladder empty. The ventral abdomen was surgically prepped and draped. Through an 18-cm ventral midline incision, the abdomen was explored. A small amount of dark, amber-colored peritoneal fluid was identified and suctioned. The large cystic mass was immediately identified associated with the left ovary. It had a smooth serosal surface with no adhesions and a single vascular pedicle. The pedicle was secured with Carmalt clamps and the ovarian mass was excised and passed off for perioperative photographs and dissection. The spherical mass measured 18 3 17 3 13 cm and weighed 2.5 kg. Thin, flocculent brown fluid poured out of the mass on incision. Two free,

oblong, soft spongy structures were within the cyst, the larger of which (8 3 6 3 6 cm) was associated with hair (Fig. 1). This corroborated the working diagnosis of a cystic teratoma or dermoid cyst. Following mass removal, the left ovarian pedicle was double ligated with 1 polyglactin 910 suture (Vicryl, Ethicon, Inc., Somerville, New Jersey 08876, USA). The right ovary was identified and appeared slightly nodular and firmer than expected. Because ovarian teratomas/dermoid cysts occur bilaterally in women in 8–15% of cases,7 a right ovariosalpingectomy was performed. The pelvis was examined and no additional abnormalities were noted. The abdomen was closed routinely in three layers using 1 polyglactin 910 suture for the abdominal wall and 3-0 polyglactin 910 for the subcutaneous and skin layers. Subcuticular skin sutures were placed and the incision was further sealed with a high viscosity paint-on tissue adhesive (SureþCloset IITM, Medical Solutions International, Inc., Greenville, South Carolina 29615, USA). The orangutan was administered a dose of meloxicam (Loxicamt, Norbrook Laboratories Limited, Newry, BT35 6PU, Northern Ireland; 0.2 mg/kg s.c.) and ceftiofur crystalline free acid (Excedet, Pfizer, Inc., New York, New York 10017, USA; 8.6 mg/kg s.c.) and recovered uneventfully following flumazenil antagonism (0.01 mg/kg i.v.). The orangutan was maintained in a recovery crate deeply bedded with straw for 48 hr and food was gradually reintroduced in the days following surgery. The animal’s behavior, respiratory rate, and otic temperature were closely monitored. Other than continued meloxicam (Lupin Limited, Pithampur, India; 0.14 mg/kg p.o. s.i.d. for 12 days), additional pain medications were not considered necessary and were not administered. The orangutan was started on a hormone replacement regimen 3.5 mo following surgery to mitigate potential problems associated with a chronic lack of estrogen and progesterone. Following some initial experimentation, the orangutan was prescribed estradiol (Watson Laboratories, Inc., Corona, California 92880, USA; 0.5 mg [0.01 mg/ kg] p.o. s.i.d. until further notice) and medroxyprogesterone acetate (Teva Pharmaceuticals, Sellersville, Pennsylvania 18960, USA; 2.5 mg [0.05 mg/kg] p.o. s.i.d. until further notice) and has shown no recognized side effects to date. Five sections of the mass with hair (6 3 5 3 4 cm plus cyst wall) were prepared, processed routinely, and 4-lm sections stained with hematoxylin and eosin were evaluated histologically (Fig. 2).

GYIMESI ET AL.—OVARIAN DERMOID CYST IN AN ORANGUTAN

Figure 2. Photomicrographs of a dermoid cyst of the left ovary in a 25-yr-old hybrid orangutan. (a) Dermoid cyst wall with hyperkeratotic epidermis (white arrow) and hair follicle (black arrow); bar ¼ 200 lm. (b) Ovarian stroma with primordial and primary follicles; bar ¼ 100 lm. (c) Granulomatous inflammation with multinucleated giant cells and cholesterol cleft (black arrow) and a hair shaft (white arrow); bar ¼ 50 lm. Hematoxylin and eosin.

Sections were composed of a thick, fibrocollagenous cystic wall with variable amounts of ovarian stroma including follicles (primordial, primary, and secondary follicles with antral fluid). The cyst

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wall was often lined by stratified squamous epidermis (2–7 cells thick) with orthokeratotic hyperkeratosis, free keratin flakes, and rare dermal hair follicles. In some sections the epidermis was replaced by thick dermal granulomatous inflammation. This included macrophages, multinucleated giant cells, and occasional interstitial and perivascular lymphoplasmacytic infiltrates. There was deep dermal thrombosis and scattered interstitial necrosis. These structures were admixed with scattered cholesterol clefts, mineral aggregates, and embedded hair shafts. All structures appeared well-differentiated and there were no histologic features of malignancy. Sections of the right ovary were histologically normal and contained a corpus hemorrhagicum. The histologic findings in the left ovary were consistent with a dermoid cyst. Several types of ovarian germ cell tumors have been described. The terms cystic ovarian teratoma and dermoid cyst are sometimes used interchangeably in radiographic and clinical settings, but histologically a teratoma is an encapsulated germ cell neoplasm composed of at least two of three potential germinal tissues including ectodermal (skin-hair, teeth, nervous tissue), mesodermal (muscle, bone, cartilage), or endodermal (lung, thyroid, pancreatic tissue) origin.9 The term dermoid cyst is applied to a germ cell tumor with only ectodermal tissue, as in this case, and this frequently shows various stages of differentiation including hair. Human ovarian teratomas/dermoid cysts are relatively common, constituting 20% of all ovarian tumors in adult women and 50% of all ovarian tumors in children.7 They are usually benign and inert; however, complications may include malignant change, torsion, rupture, and a number of more-bizarre and varied syndromes, depending on the tissue types present.2,7 Germ cell tumors are uncommon in domestic animals but occasionally occur in the bitch, mare, and cow.9 Ovarian teratomas have been reported in nonhuman primate species including a common marmoset (Callithrix jacchus),3 a vervet monkey (Chlorocebus pygerythrus),1 rhesus (Macaca mulatta),8 crab-eating (Macaca fascicularis),10 and pig-tailed macaques (Macaca nemestrina),4 Hamadryas baboons (Papio hamadryas),6 and an orangutan.5 The report in the orangutan is included in a tabulated list of primate neoplasms without histologic description. In women, cystic teratomas/dermoid cysts can occur at any age but have a propensity to be diagnosed during the reproductive years (age 20–40 yr).7 Similarly, many diagnoses in nonhuman primates have been in

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relatively young animals;6 the previous case in an orangutan was an 11 yr old.5 Given the medical history and size of the teratoma in the 25-yr-old orangutan in this report, the neoplasm may have been slowly growing for several years. Whenever abdominal palpation was performed via operant conditioning prior to diagnosis, it was done digitally through 5 3 5 cm woven welded-wire mesh. Tensing of the abdomen by the orangutan when awake, coupled with an inability to thoroughly and deeply palpate in this manner, explains how such a mass was not identified earlier. It is noteworthy that the over-the-counter laxative administered to this orangutan prior to surgery had no effect. Magnesium citrate is a saline, or osmotic, laxative that works by drawing water into the bowel. We suspect that the longer gastrointestinal tract and more-voluminous colon of orangutans, as compared to humans, accounted for this outcome. This case report demonstrates the importance of elective examinations under anesthesia, even in well-trained great apes. Some medical procedures performed via protected contact through a mesh barrier, such as abdominal palpation, cannot be done adequately. This report also illustrates the value of zoo veterinarians teaming with specialized physicians when working with nonhuman primates, particularly great apes. Acknowledgments: The authors thank Jane Anne Franklin and the Islands Mammal staff for caring for this orangutan; Jamie Huber, Elizabeth Hayden, Catherine Smolinski, and Debbie Wenger for their technical assistance; Dr. Robert Zoller, Dr. Eric Haas, and Pat Richardson for assisting with the laparotomy procedure; and Robert Kemnitz for formatting the figures.

LITERATURE CITED 1. Baskin GB, Soike K, Jirge SK, Wolf RW. Ovarian teratoma in an African green monkey (Cercopithecus aethiops). Vet Pathol. 1982;19:219–221. 2. Deffieux X, Thubert T, Huchon C, Demoulin G, Rivain AL, Faivre E, Trichot C. Complications of presumed benign ovarian tumors. J Gynecol Obstet Biol Reprod (Paris). 2013;42(8):816–832. 3. Haworth R, Jones S, Sanchez-Morgado J, Pilling A. Ovarian teratoma in a common marmoset (Callithrix jacchus). Vet Rec. 2003;153(11):332–333. 4. Lichtenwalner A, Patton D, Emerson C, Anderson D, Marit EK. Ovarian teratoma in a pigtailed macaque (Macaca nemestrina). Contemp Top Lab Anim Sci. 1997;36:86–88. 5. McClure HM. Neoplastic diseases in nonhuman primates: literature review and observations in an autopsy series of 2,176 animals. In: Montali RJ, Migaki G (eds.). The comparative pathology of zoo animals. Washington (DC): Smithsonian Institution Press; 1980. p. 549–565. 6. Moore CM, Hubbard GB, Leland MM, Dunn BG, Best RG. Spontaneous ovarian tumors in twelve baboons: a review of ovarian neoplasms in non-human primates. J Med Primatol. 2003;32:48–56. 7. Prat J. Female reproductive system. In: Damjanov I, Linder J (eds.). Anderson’s pathology, Volume 2, 10th ed. St. Louis (MO): Mosby; 1996. p. 2231–2309. 8. Rohovsky MW, Fox JG, Chalifoux LV. Benign ovarian teratomas in two rhesus monkeys (Macaca mulatta). Lab Anim Sci. 1977;27(2):280–281. 9. Schlafer DH, Miller RB. Female genital system. In: Maxie MG (ed.). Jubb, Kennedy and Palmer’s pathology of domestic animals, Volume 3, 5th ed. Philadelphia (PA): Elsevier Saunders; 2007. p. 429– 564. 10. Toyosawa K, Okimoto K, Koujitani T, Kikawa E. Choriocarcinoma and teratoma in the ovary of a cynomolgus monkey. Vet Pathol. 2000;37(2):186–188. Received for publication 17 September 2014

Ovariectomy due to a dermoid cyst in an orangutan (Pongo pygmaeus).

A large abdominal mass was identified during an elective preventative health examination in a 25-yr-old female hybrid orangutan (Pongo pygmaeus). Sono...
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