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Canine Conjunctival Tumors of Vascular Endothelial Origin

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

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Canine Conjunctival Tumors of Vascular Endothelial Origin

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  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

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

  6. 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

  7. 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

  8. 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 mm2) • Duration(in months)

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

  10. Statistical MethodsThanks 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)

  11. 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)

  12. Results • Breed (AKC classification) Control HA HSA Sporting 73 24 3 Hound 14 14 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

  13. Results • Age(years)Control HA HSA • Mean 9.1±3.2 8.4±2.6 9.1±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

  14. 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

  15. Results • Anatomic location HA HSA • 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

  16. Results • Anatomical location HA HSA • Nictitans membrane 33 13 • Leading edge 30 11 • Palpebral 3 2 • Cornea 3 1 • Unspecified 0 1 • Globe • OD 36 21 • OS 27 14 • OU 3 0 • Unknown 4 3

  17. Results • Size (mm2) HA HSA • Mean 26.4±36.7 27.4 ±26.0 • Median 12.28 20.00 • Duration (months) • Mean 4.0±4.5 3.16±3.37 • Median 3.0 1.5 • Pigmentation • none 57 38 • <10% 10 (6)* 0 • >10% 3 (2)* 0 * = cases with secondary inflammation

  18. Results • Margins HA HSA • Clean 40 12 • Dirty 23 24 • Undetermined 7 2 • Recurrence • No 24 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

  19. 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

  20. 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

  21. 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

  22. 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%)

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

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