Well-Differentiated Liposarcoma in a Bonnet Macaque (<I>Macaca Radiata</I>)

Case Report Well-differentiated Liposarcoma in a Bonnet Macaque (Macaca radiata)

Cynthia J Doane,* Paula J Johnson, and David G Besselsen

Here we describe the occurrence of a subcutaneous liposarcoma in a geriatric bonnet macaque (Macaca radiata). Clinical presentation was a rapidly growing, ulcerated, subcutaneous mass in the umbilical region of a 28-y-old intact female macaque. The mass was successfully removed through excisional biopsy, and histopathology provided a morphologic diagnosis of well-differentiated liposarcoma. The macaque recovered without complication and displayed no signs of recurrence for at least 18 mo after excision. To our knowledge, this case represents the first report of liposarcoma in a bonnet macaque.

Bonnet macaques (Macaca radiata) are native to southern In- Case Report dia, inhabiting the region south of the Godavari River.36 Despite This case report involves a 28-y-old, intact, female bonnet ma- their small geographic range, bonnet macaques outnumber rhe- caque currently engaged in a longitudinal aging and cognitive sus macaques (M. mulatta) 2:1 in India, with their less aggressive function study at the University of Arizona. The patient is con- nature contributing to successful coexistence with human popu- tinuously pair-housed with 1 or 2 compatible females. The ani- lations.27 The relative abundance of bonnet macaques in the wild mal use protocol is reviewed and approved by the IACUC and does not translate to extensive use in biomedical research, due to performed in accordance with the Animal Welfare Act and regu- Indian export exclusion since 1978 as well as significant invest- lations and the Public Health Policy. The University of Arizona ment in rhesus macaque colony expansion in the United States animal care and use program is AAALAC-accredited. in the 1980s in response to the AIDS epidemic. Only 2 substantial All study macaques receive semiannual physical exams that bonnet macaque colonies are present in the United States: the include CBC analysis, chemistry panel, parasite exam, and tu- Downstate Primate Behavior Laboratory at the State University of berculin skin test. On physical exam in December 2008, approxi- New York and the Wake Forest University Primate Center.36 The mately 1 y after arrival, a nonreducing umbilical hernia (diameter, biomedical research application of bonnet macaques is primarily 2 cm) was noted in a macaque. On subsequent semiannual exams, behavioral neuroscience and reproduction. the hernia was unchanged in size and character. The patient was In 2007, the University of Arizona acquired 12 female bonnet seropositive for Macacine herpesvirus 1 and simian retrovirus type macaques (age, 9 to 27 y) from the State University of New York D, as were several other macaques in the colony. for a longitudinal aging and cognitive function study. A second During routine exam of the patient in January 2015, the um- cohort of 4 females arrived in 2009 (age, 8 to 23 y). The current bilical mass was increased in size (diameter, 4 cm), with a 1.5-cm colony is composed of 12 captive-bred female macaques, 5 geriat- circular partial-thickness ulceration. The mass palpated with vari- ric (older than 20 y) and 7 adult. The colony is uniquely valuable able tissue density with a firm, 1-cm peduncle. In addition, the because the animals have been continuously characterized for the macaque had gained 2.7 kg in body weight between July 2014 past 9 y. Their cooperative disposition and intelligence facilitate (weight, 5.2 kg) and January 2015 (weight, 7.9 kg) due to an in- use of complex behavioral batteries to identify subtle, age-related crease in behavioral training and food rewards. Initial treatment cognitive change. of the ulceration included topical triple-antibiotic ointment daily Spontaneous malignancies in NHP are rarely reported and are and ibuprofen (10 mg/kg PO BID). Radiographs of the thorax predominated by enteric adenocarcinomas.3,21,24,32,35 Neoplasia in to check for metastasis, ultrasound evaluation of the mass, and bonnet macaques is exceedingly rare, with a single case report of surgical excision were planned. Approximately 2 wk after pre- multiple lipoma from 2005.26 In the current report, we describe the sentation, the patient was sedated (ketamine 10 mg/kg IM) for spontaneous occurrence and surgical excision of a subcutaneous ultrasonography, which confirmed a heterogeneous soft-tissue liposarcoma in a geriatric bonnet macaque. To our knowledge, mass that did not contain any fluid pockets and that was indepen- this case represents the first report of liposarcoma in a bonnet dent of the body wall. Thoracic radiographs were unremarkable. macaque. Surgical excision was performed the next day. The patient was sedated with ketamine (10 mg/kg IM) and pre- medicated with carprofen (2 mg/kg SC) and cefazolin (25 mg/kg IV). The macaque was intubated and maintained on isoflurane Received: 09 Jun 2016. Revision requested: 10 Jul 2016. Accepted: 12 Oct 2016. anesthesia at 1% to 1.5% in 100% oxygen. Additional analgesia University Animal Care, University of Arizona, Tucson, Arizona *Corresponding author. Email: [email protected] was provided with fentanyl intravenous constant-rate infusion at 176 Well-differentiated liposarcoma in a bonnet macaque

0.5 to 1 μg/kg/h. A balanced crystalloid solution was delivered intravenously at 5 to 10 mL/kg/h. The abdominal area was shaved, initially cleaned with chlorhexidine, and prepared for surgery by using alternative cleansing with povidone–iodine and alcohol. An elliptical incision through the skin was made adjacent to the abdominal mass. By using blunt dissection, the mass was excised and the supporting connective tissue stalk was isolated. The stalk (diameter, 1.5 cm) was ligated by using 4 transfixing sutures of 2-0 Polysorb (Covidien, Minneapolis, MN) and transected to allow easy removal of the mass. A 3-layer closure was used to decrease potential dead-space. The deepest later of subcutaneous tissues were closed by using 2-0 Polysorb suture in a simple interrupted pattern. The next layer was closed with 2-0 Polysorb interrupted horizontal mattress pattern. The skin was close with a continu- ous intradermal suture of 2-0 PDS II (Ethicon, Somerville, NJ), with surgical adhesive (Tissumend II, Veterinary Products Labo- ratory, Phoenix, AZ) applied at each incision end. The animal recovered from surgery uneventfully. Postoperative care included buprenorphine SR (single dose of 0.2 mg/kg SC; 10 mg/mL, ZooPharm Lab, Windsor, CO), ibuprofen (10 mg/kg PO BID daily for 3 d), and cephalexin (25 mg/kg PO BID for 5 d). The incision was monitored twice each day for the first 3 d and then Figure 1. Ulcerated umbilical mass after surgical excision. once daily until healed. Gross pathology revealed a spherical (diameter, 4 cm), yellow- ish, subcutaneous umbilical mass with skin ulceration that was interpreted as lipomatous (Figures 1 and 2). Representative sec- tions of the mass inclusive of surgical margins were processed, paraffin-embedded, and stained with hematoxylin and eosin. Histopathology revealed the tissue to be a multilobulated mass separated by thick fibrovascular cords, with lobules predomi- nantly composed of well-differentiated adipose cells and smaller regions of less-differentiated spindle-shaped cells arranged in streams (Figure 3). Neoplastic cells in less-differentiated regions had indistinct cell borders, frequently contained a small clear cy- toplasmic vacuole, and had vesicular nuclei that contained 1 or 2 small nucleoli. Mild anisocytosis and anisokaryosis were ob- served. Mitoses ranged from 0 to 2 per high-power field, with an average of fewer than 1 per high-power field. In addition, mild to moderate lymphocytic perivasculitis and arteritis with fibrinoid necrosis or medial hypertrophy were present randomly through- out the mass. Evaluation of surgical margins indicated complete excision. The morphologic diagnosis for the mass was well-differentiated liposarcoma. The patient receives a complete physical exam every 6 mo Figure 2. Umbilical mass on cross-section. as indicated by the colony preventative medicine protocol. At 14 mo after surgical excision, she was diagnosed with mitral valve insufficiency through auscultation (grade 3/6 left apical Discussion In humans, liposarcoma is the most common soft-tissue ma- systolic murmur) and echocardiography and was prescribed lignancy, accounting for approximately 20% of all sarcomas.9 enalapril (0.5 mg/kg BID). At 18 mo after surgery, the patient Liposarcomas occur most commonly in the extremities and ret- was diagnosed with type 2 diabetes mellitus after a 2-wk pe- roperitoneum.28 Because liposarcomas are generally resistant to riod of weight loss prompted evaluation. At that time, fasting chemotherapy, surgical excision is the treatment of choice. The blood glucose was 257 mg/dL, and hemoglobin A1c was 8.4%. World Health Organization recognizes 4 liposarcoma subtypes: Immediate dietary modification was implemented with good well-differentiated or atypical lipomatous tumor; dedifferentiated response, and a 1-mo recheck of fasting blood glucose indi- liposarcoma; myxoid (or round-cell) liposarcoma; and pleomor- cated reasonable control (156 mg/dL). At the time of submis- phic liposarcoma.15 Each subtype has a distinct clinical trajectory. sion for publication, there is no local recurrence of neoplasia For example, well-differentiated liposarcoma is locally aggressive and recheck thoracic radiographs remain unremarkable at 18 and does not metastasize, whereas myxoid liposarcoma rapidly mo after surgery. metastasizes to bone and soft tissue.7-9

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firmed through an ultrasound-guided fine-needle aspirate. Not all suspect masses in the colony are diagnosed by biopsy at this time but have a presumptive diagnosis of lipoma in light of slow growth, location in the subcutis, and homogeneous soft texture on palpation. In addition to the seemingly high incidence of lipoma, the clinical case we report here suggests an increased risk for adipose neoplasia in this colony. Whether a genetic predisposition is present in this species, as seen in humans, is unclear. With people and dogs, our patient shares advanced age as a risk factor. In addition, she is infected with a known oncogenic retrovirus, although simian retrovirus infection has not been linked to liposarcoma. It is interesting that the umbilical mass, which was unchanged for 6 y, doubled in size and ulcerated during the same 6-mo period that the patient rapidly gained weight, suggesting a link to increased body condition. Liposarcoma in humans is not associated with obesity in the current literature. This case represents the first report of well-differentiated li- Figure 3. (A) Histopathology of well-differentiated liposarcoma. Ar- posarcoma in a bonnet macaque. The history and presentation rows indicate mitotic figures. Hematoxylin and eosin stain; magnifica- of this case, as well as the increased frequency of lipoma in this tion, 50×. (B) Higher magnification of mitotic figure. Hematoxylin and colony, require additional consideration. Questions remain re- eosin stain; magnification, 100×. garding age, body condition, genetic predisposition, and retroviral involvement. If the tendency seen in our group proves to be Liposarcomas are rare in animals and occur most frequently 2,4,11 species-wide, bonnet macaques may serve as a useful model for in geriatric dogs. A few case reports describe liposarcomas human multiple lipoma and liposarcoma. in other species, including cats,6,37 cattle,29,34,38 ferrets,14,16,17 guinea pigs,30 horses,20 rabbits,40 rats,5 and various birds.13,25,31,33 The veterinary literature is well summarized in a 2015 review article.11 In Acknowledgments veterinary species there is no standardized classification scheme, We thank the staff at University Animal Care for providing veterinary and typically 3 subtypes are reported: well-differentiated; myx- and husbandry support to this colony. We also thank Becky Schwartz for her editorial contributions. oid; and pleomorphic.4,11,19 A single case report describes a round- cell variant of myxoid liposarcoma in a Japanese macaque (M. fuscata).21 References Risk factors for liposarcoma in people include advanced age, 1. American Cancer Society. [Internet]. 2016. Sarcoma: Adult Soft previous radiation treatment, and exposure to toxins.1 Liposar- Tissue Cancer. [Cited 4 April 2016]. 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