1. Canine Conjunctival Tumors of Vascular Endothelial Origin RR Dubielzig and CG Pirie, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Madison-Wisconsin

2. Introduction Primary conjunctival vascular tumors are infrequently reported, often diagnosed as hemangioma (HA) or hemangiosarcoma (HSA) Canine most common, however, equine, feline, and other species reported Knowledge of their biological behavior and potential risk factors is limited

3. Introduction Develop within adult to geriatric age group (mean 8.5 years) No reported breed or sex predilection Leading edge of nictitans membrane or lateral bulbar conjunctiva (+/- cornea) Unilateral distribution, however, bilateral involvement reported

4. Introduction Primary conjunctival vascular tumors (HA and HSA) are both considered unlikely to metastasize but with the potential to recur locally. They are distinguished by standard criteria Predisposing risk factors remain unknown, although UV radiation has been proposed

8. Purpose To evaluate the epidemiology of canine primary conjunctival hemangiomas and hemangiosarcomas and to examine potential predisposing risk factors

9. Materials and Methods 108 cases (70 HA, 38 HSA) were selected from a database consisting of 8,300 canine cases submitted to the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) during 1989-2004 216 controls selected from same database, using standardized sampling, during 1989 - 2004 Follow up information available for 49 cases (86 replies), obtained via facsimile or telephone conversation

10. Material and Methods Breed (individual and accepted AKC classification) –sporting, hound, working, terrier, toy, non-sporting, herding, and miscellaneous Age Gender Geographical location (comparing calculated UV levels and geographical distribution, by state) data provided by NOAA, consisting of monthly means for 52 US major cities during 1995 to 2003

11. Material and Methods Anatomic location –superior, inferior, medial, and lateral bulbar or palpebral conjunctiva –nictitans membrane –cornea Globe (OD, OS, OU) Size (surface area in mm 2 ) Duration (in months)

12. Materials and Methods Epithelial pigmentation –histological grading system None, 10% with or without changes of chronic irritation Diagnosis (hemangioma vs. hemangiosarcoma) Margins –clean, dirty, undetermined Ancillary therapy (laser, cautery, cryotherapy) Recurrence

13. Statistical Methods Thanks to Chet Thomas Logistic regression model (Proc Logistic) adopted to describe association between response variable (diagnosis) and a set of explanatory variables Backward elimination procedure employed using Wald chi-square (p  0.05) Likelihood ratio and Pearson goodness-of-fit chi-squares (determine if the model adequately fit the data)

14. Results Breed (individual) Controls 52 purebred and mixed breeds represented Mixed breed (44), Labrador (24), and Golden retriever (23) Hemangioma (HA) 0.84% total and 2.01% of neoplasia COPLOW cases (canine) 27 purebred and mixed breeds represented Basset hound (7), English springer spaniel (6), Boxer (5), Labrador retriever (5) English setter (4) Hemangiosarcoma (HSA) 0.46% total and 1.14% of neoplasia COPLOW cases (canine) 24 purebreds and mixed breeds represented Beagle (3) and Dalmatian (3)

15. Results Breed (AKC classification) ControlHAHSA Sporting 7324 3 Hound 1414 7 Working 20 8 8 Terrier 13 3 3 Toy 16 3 1 Non-Sporting 24 3 4 Herding 12 8 5 Miscellaneous (mixed) 44 7 7

16. Results Age (years)ControlHAHSA –Mean9.1±3.28.4±2.69.1±2.8 –Median 9.25 8 9 Gender –Male 34 10 9 –Male,castrated 66 27 12 –Female 17 5 4 –Female,spayed 81 24 13 –Unspecified 17 4 0

17. Results Geographical distribution Controls –California(32), Florida(25) New York(21) Hemangioma –California(10), Florida(6), Minnesota(6) –31% of cases Hemangiosarcoma –California(9), Florida(6), Utah(4) –50% of cases

18. Results Anatomic locationHAHSA –Bulbar conjunctiva 31 22 Temporal 19 14 Nasal 5 1 Superior 2 1 Inferior 2 0 Unspecified 3 6 –Palpebral conjunctiva 3 1 Superior 0 1 Inferior 3 0

19. Results Anatomical locationHAHSA –Nictitans membrane 33 13 Leading edge 30 11 Palpebral 3 2 –Cornea 3 1 –Unspecified 0 1 Globe –OD36 21 –OS27 14 –OU 3 0 –Unknown 4 3

20. Results Size (mm 2 )HAHSA –Mean26.4±36.727.4 ±26.0 –Median12.2820.00 Duration (months) –Mean4.0±4.53.16±3.37 –Median3.01.5 Pigmentation –none5738 –<10%10 (6)* 0 –>10% 3 (2)* 0 * = cases with secondary inflammation

21. Results MarginsHAHSA –Clean40 12 –Dirty23 24 –Undetermined 7 2 Recurrence –No24 7 (14 C, 8 D[1]*, 2 U) (7 D[2]*) –Yes 3 11 (2 C, 1 D)(5 C, 6 D) C=clean, D=dirty, U=undetermined [ ]*= number of cases undergoing surgical revision

22. Statistical Analysis Logistic regression model, case vs control status –Breed class (p = 0.0010) Hound (OR = 4.97), Herding (OR = 3.36), Working (OR = 3.08), increased risk of tumor development, as compared to mixed breeds Basset hound, Boxer, English setter and springer spaniel, within hemangioma and Dalmatians, with hemangiosarcoma populations, over-represented (> 5%) –UV exposure(p = 0.1215) approached significance in restricted model (p = 0.696) liner trend (p = 0.0147), with risk of tumor development at UV exposure of 4,5, and 6, as compared to 3, being 0.96, 1.84, and 1.90 times more likely

23. Conclusions Conjunctival tumors of vascular origin are under-reported 2.01% (HA) and 1.14% (HSA) of COPLOW neoplasia submissions Age at onset, regardless of diagnosis, 8.6 years No sex predilection

24. Conclusions Etiology remains unknown, with UV as proposed risk factor –Trend to develop in breed classes with likely increase outdoor activity (Hound, Herding, Working) –Strong predilection site, leading edge of nictitans membrane (38.0%) and lateral bulbar conjunctiva (30.6%), with tendency to involve the right conjunctival surface –All 38 HSA and 57 (81.4%) HA cases demonstrated lack of pigmentation –Statistical trend to occur in states with high uv exposure

25. Conclusions Histological diagnosis is predictive of behavior –Hemangiosarcoma, greater size and shorter duration, demonstrating locally aggressive tissue involvement –Increased risk of recurrence with hemangiosarcoma (11/20, 55%), as compared to hemangioma (3/29, 10.3%)

26. Acknowledgements Chet Thomas Amy Knollinger Craig Long, NOAA VMDB for provision of submission data All those who provided follow-up data