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

• 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

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

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

Purpose

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

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

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

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)

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

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)

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)

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

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

Results• Geographical

distributionControls

– 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

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

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

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

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

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

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

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

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%)

Acknowledgements

• Chet Thomas• Amy Knollinger

• Craig Long, NOAA• VMDB for provision of submission data• All those who provided follow-up data