VIRAL PAPILLOMA AND SQUAI'IOUS CELL CARCINOIVIAS IN SNOW LEOPARDS(Uncio uncia)

Janis Ott Joslin, DVM,t* Michsel Gorner, DVM, Dipl ACVP,2 Darin Collitts, DVM,t Elizabeth Kannko,

DVlt[,r Kenneth Sinabaldi, DVfu[,a Karelle LIeleo, DVfuI,s Richard ll[ontali, DVilI,6 John Sundberg, DVtr[,phD,7 A. Bennett Jenson, MD,E Shin-je Ghin, PlrD,E Beth Davidov, DVM,e Atut M, Hargis, DVM, MS,Dipt ACVP,'0 Keitlt ll/est, DVIV," Ted Clark, DVM, IgtVSc, Dipl ACVP,I2 and Debbera Haines, DVIW,PltDtz

Illoodland Park Zoological Gardens, 5500 Phinney Avenue North, Seattle,ll/,4 98103 USA;2Northx'estZooPath, 18210 ll/averly Drive, Snohonish, lyA 98296 USA; 3SnolYood Veterinary Hospital, 17954ll/oodinville-Snohomish Road, ll/oodittyille, WA 98072 USA; lAnimal Surgical Clinic, 4102 StonewayAvenue North, Seattle, WA 95103 USA; sVeterinary Oncologt Services,79l5 ISyu Place, Redmond,llA98052 USA;6The National Zoological Park, Depart,nent of Pathologt, 3001 Connecticut Avenue, NPI/,Il/ashirtgton, D.C. 20008 USA;7The Jackson Laboratory,,600 Main Street, Bar Harbor, ME 04609 USA;sGeorgetown IJniversity, Departnrent of PathoIo91,, School of Medicine ond Dentistry,3900 Resemoir RoadNE,llashirtgtort, D.C. 20007 USA;eAninrul Emergency ond Referral Center, I95II 24'h Avenue ll/est,Lynnwood, lyA 98036 USA; I0DermatoDiogrrostics, 17905 Tolbot Road, Edntonds, lI/A 98026 USA;ItPriurie Diogtrostic Sen,ices, Saskatoon Laboratories, 52 Cantpus Drite, Saskatootr, Saskatchewan,S7N5Bl, Canada;t)fJtriversity of Saskatoon, Department of Veterirrsry Microbiology,52 Contpus Drive,S askutc h ex,s n, S TN 5 81, Ca noda

Abstract

Papil lomaviruses (PV) have been isolated in humans, and a number of domestic and nondomesticspecies of animals. ' t ' 'n These viruses are relatively species specif ic and are associated rvithprol i ferative lesions of the skin and the mucous membranes. In most species, viral papil lomas (VP)are benign, but in some the papillomas have been shorvn to transform to malignant tumors such assquamous cell carcinomas (SCC).r0'r8're

Viral papillomas in felids are uncommon. Recently papillomas were restricted to the oral cavity ofdomestic cats (Fells dornesticus), Asiatic lions (Panthera leo persica), snorv leopards (U. uncia,),Florida panthers (F. concolor), bobcats (F. nfus), clouded leopard (Neofelis nebulosa), but thelesions also have been found on the skin of domestic cats and snorv leopat6t.2'3'8'rr 'r6'r7 Unti lrecently, only in the domestic cat were these papillomas shown to be associated with malignanttransformationro.

At Woodland Park Zoological Gardens (WPZ), five individual snow leopards have been identifiedwith raised, thickened, irregular, black lesions on the skin, mainly on the face and forelimbs, rangingin size from 2-15 mm in diameter. In 1989, the f irst lesions were identif ied on a breeding maleduring a routine physical exam. Biopsy results identified the lesions as papillomas of likely viraletiology, and papillomavirus antigen was identified by immunohistochemistry (lHC). Viral inducedpapillomas rvere identified on the mate of this animal during a routine physical exam in 1992. In1998, the breeding male developed mult iple SCC on its feet and died due to septicemia that l ikely

2OOO PROCEEDINGS AAZV AND IAAAM JOINT CONFERENCE 155

electrocautery is not recommended since the papillomas, which were ablated with electrocautery,

appeared in itris case to also have seeded the surrounding skin causing the production of more

pupitto*ur circling the site of the ablation. Any non-healing wounds and oral swellings should be

f iopsiea to rule out SCC. One should be especially suspicious of an early transformation of the

pupillorur to a SCC if the raised thickened pigmented tissue can be easily scraped off leaving an

ul..t, since with the typical papilloma, the raised area is firmly attached to the underlying dermis.

Surgical biopsies of thele eaily lesions will confirm the diagnosis of SCC. once a diagnosis of SCC

is rn'ade, aggressive surgical excision should be performed on all suspicious lesions. Follow up

examinations should be made at 6-wk intervals to evaluate for further tumor development.

Unfortunately, as indicated in the medical survey, the prognosis for these cases is poor.

It is because of this poor prognosis that the authors are investigating the possibility of developing

a recombinant vaccine for snow leopards in order to control the spread of this virus in the captive

population worldwide. Recombinant papilloma virus vaccines have been developed by two of the

authors, Jenson and Ghim, against carcinogenic and non-carcinogenic human^papilJomavirus, bovine

fibropapillomavirus, equine papillomas, and canine oral papillomavirus.5-t'e'r5're'2r

Identification of papillomavirus in Asiatic lions and in pygmy chimpanzees (Pan paniscus)have

excluded them from being brought into the United States and being represented in the Species

Survival Plans for these species (A.B. Jenson, pers. comm.). This study could be used as a model

for viral infection in other cats and thus ultimately help these other species, some of which are also

highly endangered.

ACKNOWLEDGMENTS

This work was supported by a grant from the Woodland Park Zoological Sociery. We thank all of the veterinarians atinstitutions holding snow leopards who have supplied us with copies of their medical records and biopsy specimens,

Histology Consulting Service for histopathology slide preparation, Dan Wharton and Evon Hekkala for their assistancewith the ipidemiology analysis, Barbara Powers, DVM, PhD, Dipl ACVP from Colorado State College of Veterinary

Medicine who supplied pathology specimens, Susan Walls for herassistance with this manuscript and the following staffatWPZ who assisted in the care of these animals: Helen Shewman, Peter lv{clane, Heidi Frohring, Debbera Stecher,James Scott, Amy Brandt, Roz Sealy, Linda Shipe, Harmony Frazier, Carol Strickland, Kathe Rasler, Neal Duncan,Cheryl Clarke, Mike Waller, Bruce Bohmke, and Lee Werle.

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originated in the infected areas in the neoplastic foci. Papil lomavirus antigen rvas also identif iedbi, IHC in one SCC from this male.

In 1996 trvo offspring of this pair that u'ere sent to another institution developed SCC and wereeuthanatized. Additionally, another nrale snorv leopard aiso housed at WPZ died of oral SCC inI 996.

All fir'e of the snow leopards from WPZ that had VP, eventually developed SCC. Of these five, onlyone, a l6-yr-old female mate, n'as diagnosed early enough to atternpt a significant treatment basedon treatment regimes used in domestic cats.r 'r2'r3 On 20 November 1999 this female, which hadpapil lomas identif ied in 1992, was diagnosed with early signs of SSC on her feet. These lesionsappeared to be papillomas but on closer examination, the black, rough irregular surface of severallesions could be easily scraped off leaving a raw sore. In the usual papil loma lesions, the blacksurface was firmly adhered to the dermis and could notbe scraped off. Biopsies of these lesionssho*'ed transition zones of SCC arising from VP.

Our treatment of this animal consisted of laser surgery for the SCC on l5 December 1999 withfol los,up examinations to check for SCC on l4 January and 4 Apri l 2000. At these exams, theres'as only one small area suspicious of an early SCC, rvhich on histology \r'as confirmed to be apapilloma. Any papilloma lesion that u'as found was removed by electrocautery or by surgicalexcision. On 14 May the animal u'as examined for anorexia and lethargy and was euthanatized dueto kidney failure. There was no evidence of SSC found on necropsy and there were a few small, 2-5mm, papilloma lesions found on the forearms and head of this animal.

Concurrently, in 1998, as a fol lou'up to a survey done in 1987, a request for medical records forsnorv leopards for the last l0 yr *'as sent to all holders of Snow Leopard Species Survival PIan(SSP) animals (76 instirutions), as part of the SSP medical review. Medical records were reviewedfrom 66 institutions (an 87% return) for 424 animals of which 230 had died. Twenty-oneindividuals died with SCC. This accounted forgYo of the mortalities in the survey. In addition,there were fwo snow leopards identified with oral papillomas, one of these leopards is a new animalatWPZthat has not developed skin lesions. Oral papillomas were similarto those described in otherexotic felids'6'r7 and are pale, small (l-5 mm) nodules most commonly found under the tongue. Inaddition, oral papillomas have been documented in two snow leopards in a zoo in Russia.r6

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