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Proceedings of the 36th World Small Animal Veterinary Congress

WSAVA

Oct. 14 - 17, 2011 Jeju, Korea

Next Congress:

Reprinted in IVIS with the permission of WSAVA http://www.ivis.org

OP-B11

TUMORS OF THE CANINE GLOBE

Richard R. Dubielzig, DVM, Diplomate ACVP

Department of Pathobiological Sciences, School of Veterinary Medicine

University of Wisconsin-Madison, Madison, WI, USA

Introduction: This report is a concise summary of primary ocular tumors and their relative frequency in

dogs, which is derived from the archives of the Comparative Ocular Pathology Laboratory (COPLOW) a large

ocular pathology database.

It is important to have a regional understanding of ocular neoplasia because similar tumors may have a

different clinical course depending on location, particularly regarding melanocytic tumors. Melanocytoma

(defined as a benign melanocytic tumor) and malignant melanoma of the canine globe have the potential to be

locally aggressive, yet enucleation is usually curative for both.4 Malignant melanoma is common in the

conjunctiva and often recurs locally. In contrast, a pigmented tumor in the eyelid is more likely melanocytoma

than a malignant melanoma.¹ Hemangiosarcoma in the globe is likely to be a metastatic tumor but primary

hemangioma and hemangiosarcoma of the conjunctiva occur commonly. Although they may recur if

inadequately excised, they have very low metastatic potential.

In the COPLOW database, the population of dogs with primary ocular neoplasia was comparable to the

total database population, which included all ocular pathology submissions (inflammatory diseases, congenital

diseases, trauma, primary and metastatic neoplasia, etc.). There were 6067 cases of primary ocular neoplasia in

dogs with a definitive histopathologic diagnosis. Tumors of the globe accounted for 2851 (47.0%) cases and the

majority of these were either melanocytic (1842, 64.6%) or iridociliary epithelial tumors (836, 29.3%).

Conjunctival and eyelid tumors accounted for 1535 (25.3%) cases and 1399 (23.1%) cases, respectively. Finally,

there were 282 (4.6%) orbital tumors.

No gender-specific patterns emerged for any individual tumor type in dogs. Most tumors had a typical age

distribution with middle-aged and old dogs most frequently affected. Mean and median ages were 9.2 and 9.5

years, respectively.

A positive correlation based on breed, as determined by odds ratio, was significant for several tumors. The

most notable breed predispositions arose in spindle cell tumor of blue eyed dogs (Siberian husky and Australian

7812011 WSAVA·FASAVA World Congress Proceedings

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ICC Jeju, Korea

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36th World Small Animal Veterinary Congress 2011 - Jeju, Korea

shepherd), corneal squamous cell carcinoma (pug), conjunctival hemangiosarcoma (border collie, Australian

shepherd, English setter, Basset hound, beagle and boxer), and eyelid melanoma (vizsla and Doberman pinscher). The Siberian husky is significantly less likely to have uveal melanocytic tumors.

The malignancy of melanocytic tumors varied with anatomic location in the eye. Melanocytic tumors in the

uveal tract, limbus, and eyelid were more often benign than malignant. There were 1458 of 1842 (79.2%)

melanocytic tumors of the uveal tract that were diagnosed as melanocytoma, and the remaining 384 (20.8%)

were malignant melanoma. Limbal melanocytoma accounted for 341 of the 343 limbal melanocytic tumors

(99.4%). Of the 149 eyelid melanocytic tumors, 126 (84.6%) were melanocytoma and 23 (15.4%) were

malignant melanoma. The conjunctiva was the only location where malignant melanoma (180, 88.2%) was

more common than benign melanocytoma (24, 11.8%).

Primary Tumors of the Globe

Melanocytic Tumors of the GlobeUveal melanocytoma was approximately four times more common than malignant melanoma of the uvea.

With respect to location within the uveal tract, anterior uveal (iris and/or ciliary body) melanocytic tumors are at

least ten times more common than those in the choroid. Melanocytoma frequently invades the sclera and may

extend into the episclera in advanced cases. Malignant uveal melanoma exhibits pleomorphism and may be

locally invasive, although metastasis is uncommon. Malignant melanoma is more frequently amelanotic than

melanocytoma. Enucleation with complete excision is generally curative for both melanocytoma and malignant

melanoma of the uvea.4

Iridociliary epithelial tumorsIridociliary epithelial tumors (IET) are the second most common intra-ocular tumor of dogs. Canine

iridociliary epithelial tumors vary considerably with respect to pigmentation, invasiveness and morphology

(solid vs. papillary). The definition of adenoma versus adenocarcinoma is based on histologic evidence of

scleral invasion in the latter. We did not differentiate between adenoma and the scleroinvasive adenocarcinoma

in this review, although previous studies suggest that IET adenoma is approximately 6-8 times more frequent

than adenocarcinoma.5,6 Deposition of a thick, often arborizing, periodic acid Schiff (PAS)-positive basement membrane is often helpful in diagnosing poorly-differentiated or extensively necrotic IETs in dogs. Like native

iridociliary epithelium, canine iridociliary epithelial tumors are generally positive for vimentin and negative for

cytokeratin immunohistochemical stains. However, there is some tendency for the more invasive iridociliary

adenocarcinomas to coexpress cytokeratin and vimentin.6,7

Iridociliary epithelial tumors, including the invasive adenocarcinoma, are clinically benign and generally

well-differentiated. However, a previous study identified 16 cases of “pleomorphic” iridociliary

adenocarcinomas.5 The term pleomorphic iridociliary adenocarcinoma applies to a similar malignant primary

uveal tumor in humans, and is the only ocular tumor in humans associated with prior trauma.8 In dogs, the

diagnosis applies to iridociliary tumors with pronounced cellular and nuclear features of malignancy and

infiltrative behavior. They often arise in globes with long-standing intraocular disease, including previous

intracameral gentamicin injection.5 Pulmonary metastasis was previously reported in one of the cases of

pleomorphic iridociliary adenocarcinoma reported here.9

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36th World Small Animal Veterinary Congress 2011 - Jeju, Korea

Spindle cell tumor of blue-eyed dogsSpindle cell tumor of blue-eyed dogs (SCTBED) is the third most common intra-ocular tumor in dogs. In

dogs that have at least a partially blue iris, these tumors arise diffusely in the iris, may extend to the ciliary body,

and rarely involve the choroid. SCTBED are frequently not recognized clinically as neoplastic disease and may cause secondary glaucoma without an obvious mass lesion. Immunohistochemistry staining characteristics

(GFAP positive and Melan A negative) is consistent with Schwann cells of non-myelinating nerves, furthermore,

the tumors are morphologically consistent with a schwannoma.10 SCTBED must be distinguished from other

intra-ocular spindle cell tumors of dogs, namely, melanocytic tumors and metastatic sarcomas. There are definite

breed predispositions for SCTBED, generally any breed in which blue eye color occurs regularly. Siberian

husky dogs and Australian shepherds are over-represented with respect to SCTBED in the COPLOW collection.

Corneal Squamous Cell CarcinomaThe cornea may be the primary site of squamous cell carcinoma (SCC), particularly in dogs with long-

standing keratitis.11-14 Corneal SCC may occur in situ or as an extension of conjunctival SCC. There is some

evidence that dogs treated with topical medications for keratoconjunctivitis sicca at increased risk.15

Brachycephalic breeds are reported to be predisposed to corneal squamous cell carcinoma,12,14-15 and we found

a statistically significant association in pugs.

Primitive Neuroectodermal TumorIntra-ocular primitive neuroectodermal tumors (PNET) are poorly differentiated embryonal tumors of

neural tissue origin and include medulloepithelioma and retinoblastoma. Of the 27 cases of ocular canine PNET

reported here, most (11) have a pattern characteristic of medulloepithelioma. Medulloepithelioma is rare in

domestic animals, reported most frequently in dogs and horses.3 Medulloepithelioma may be fairly well-

differentiated, resembling an iridociliary epithelial tumor. Like ciliary body epithelium, cells are negative for

cytokeratin.7

True retinoblastoma is almost exclusively a human disease, and is often associated with mutation of the

retinoblastoma (rb) tumor suppressor gene. Of the 27 PNET tumors included here, two were diagnosed as

retinoblastoma. They must be distinguished from medulloepithelioma based on strict morphologic criteria.16

GliomaGliomas associated with the eye are rare in both the dog and cat. Ocular gliomas may be associated with

either the retina or the optic nerve and may extend up the optic nerve tract toward the optic chiasm. They are

generally astrocytomas with positive immunolabeling with glial fibrillary acidic protein (GFAP), and rarely

oligodendroglioma.17

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TUMORS OF THE CANINE GLOBE

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36th World Small Animal Veterinary Congress 2011 - Jeju, Korea

References:1. Dubielzig RR, Ketring, KL, McLellan, GJ et al. Veterinary Ocular Pathology: A Comparative Review.

Edinburgh: Saunders Elsevier, 2010.

2. Willis AM, Wilkie DA. Ocular oncology. Clinical Techniques in Small Animal Practice 2001; 16(1): 77-85.

3. Dubielzig RR. Tumors of the eye. In: Tumors in Domestic Animals, 4th edition (ed: Meuten DJ), Iowa State Press: Ames, 2002; 739-54.

4. Giuliano EA, Chappel R, Fischer B, et al. A matched observational study of canine survival with primary

intraocular melanocytic neoplasia. Vet Ophthalmol 1999; 2: 185-190.

5. Bell CM, Dubielzig RR. Canine Iridociliary Epithelial Tumors: A Morphologic Case Series of 702 Cases, in proceedings. 60th Annual Conference of the American College of Veterinary Pathologists 2009; abstract

#172.

6. Dubielzig RR, Steinberg H, Garvin H, et al. Iridociliary epithelial tumors in 100 dogs and 17 cats: a morphological study. Vet Ophthalmol 1998; 1: 223-231.

7. Klosterman E, Colitz CM, Chandler HL, et al. Immunohistochemical properties of ocular adenomas, adenocarcinomas and medulloepitheliomas. Vet Ophthalmol 2006; 9(6): 387-94.

8. Laver NM, Hidayat AA, Croxatto JO. Pleomorphic adenocarcinomas of the ciliary epithelium:

Immunohistochemical and ultrastructural features of 12 cases. Ophthalmology 1999; 106(1): 103-110.

9. Zarfoss MK, Dubielzig RR. Metastatic iridociliary adenocarcinoma in a Labrador Retriever. Vet Pathol 2007; 44: 672-676.

10. Zarfoss MK, Klauss G, Newkirk K, et al . Uveal spindle cell tumor of blue-eyed dogs: an

immunohistochemical study. Vet Pathol 2007; 44: 276-284.

11. Busse C, Sansom J, Dubielzig RR, et al. Corneal squamous cell carcinoma in a Border Collie. Vet Ophthalmol 2008; 11: 55-58.

12. Montiani-Ferreira F, Kiupel M, Muzolon P, et al. Corneal squamous cell carcinoma in a dog: a case report. Vet Ophthalmol 2008; 11(4): 269-72.

13. Latimer KS, Kaswan RL, Sundberg JP. Corneal squamous cell carcinoma in a dog. J Am Vet Med Assoc

1987; 190: 1430–1432.

14. Bernays ME, Flemming D, Peiffer RL. Primary corneal papilloma and squamous cell carcinoma associated

with pigmentary keratitis in four dogs. J Am Vet Med Assoc 1999; 214: 215–217.

15. Dubielzig RR, Schobert CS, Dreyfus JM. Corneal squamous cell carcinoma in dogs with a history of chronic keratitis, in proceedings. Annual Meeting of the American College of Veterinary Ophthalmologists 2008;

abstract #101.

16. Peiffer RL, Simons KB. Ocular Tumors in Animals and Humans. Ames: Iowa State Press, 2002.

17. Naranjo C, Schobert C, Dubielzig RR. Canine ocular gliomas: a retrospective study. Vet Ophthalmol 2008; 11(6): 356-362.

784 2011 WSAVA·FASAVA World Congress Proceedings

14(Fri) ~ 17(Mon) October 2011

ICC Jeju, Korea

2011 WSAVA·FASAVA World Congress

www.wsava2011.org

Reprinted in IVIS with the permission of WSAVA Close this window to return to IVIS

36th World Small Animal Veterinary Congress 2011 - Jeju, Korea