Veterinary Ophthalmology (2015) 1–6
DOI:10.1111/vop.12273
Third eyelid gland neoplasms of dogs and cats: a retrospective histopathologic study of 145 cases D. Dustin Dees,* Charles S. Schobert,† Richard R. Dubielzig† and Timothy J. Stein‡ *From Eye Care for Animals, 12419 Metric Blvd, Austin, TX 78758, USA; †Comparative Ocular Pathology Laboratory of Wisconsin, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA; and ‡Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA
Address communications to: D. D. Dees Tel.: (512) 335-3937 Fax: (512) 628-9006 e-mail: [email protected]
Abstract Purpose To describe the various types of primary neoplasms affecting the third eyelid (TEL) gland of dogs and cats. Methods A retrospective search of the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) database was performed. Veterinary ophthalmologists, primary care veterinarians, and, when appropriate, owners were contacted for patient follow-up information. Patient data points collected included species, age, sex, breed, laterality, tumor type, surgical margins, recurrence, metastasis, and length of followup. Results A total of 127 canine and 18 feline cases met the inclusion criteria. The most common canine TEL gland tumor was adenocarcinoma (n = 108; 85.0%) followed by adenoma (n = 18; 14.2%) and squamous cell carcinoma (SCC) (n = 1; 0.8%). For canine cases with follow-up information available (n = 62), 8.1% had confirmed or suspected metastasis and 11.3% had confirmed or suspected local recurrence of disease. The most common feline TEL gland tumor was adenocarcinoma (n = 15; 83.3%) followed by SCC (n = 3; 16.7%). For feline cases with follow-up information available (n = 9), 40.0% had confirmed or suspected metastasis and 30.0% had confirmed or suspected local recurrence of disease. Conclusions This study determined that adenocarcinoma was the most common third eyelid gland tumor in both dogs and cats. The overall survival times were less, and metastatic occurrence and recurrence rates appeared to be higher for feline tumors as compared to those diagnosed in dogs. This is the first report of SCC originating from glandular ductular epithelium. Key Words: adenocarcinoma, adenoma, canine, feline, squamous cell carcinoma, third eyelid gland
INTRODUCTION
The third eyelid (TEL) or nictitating membrane is composed of numerous tissue types including conjunctival epithelium, vascular substantia propria, lymphoid tissue, supporting hyaline cartilage, and associated glandular tissue which contributes to lacrimation. Numerous types of TEL neoplasms have been reported in the veterinary literature including transmissible venereal tumor, squamous cell carcinoma, melanocytoma, melanoma, lymphoma, plasmacytoma, hemangioma, hemangiosarcoma, mast cell tumor, and myoepithelioma in dogs; squamous cell carcinoma, hemangioma, © 2015 American College of Veterinary Ophthalmologists
hemangiosarcoma, melanoma, adenocarcinoma, mast cell tumor, and fibrosarcoma in cats; and squamous cell carcinoma, lymphoma, adenocarcinoma, hemangiosarcoma, lymphangiosarcoma, and basal cell tumor in horses.1–34 The majority of these neoplasms originate from the surface tissues (conjunctival and lymphoid tissues) or the stroma of the substantia propria.1,2,4,5,8–10,12–21,23,25,26,28–30,32–34 Those that originate in the TEL gland are less common and include adenocarcinoma, adenoma, plasmacytoma, myoepithelioma, and lymphoma.3,6,11,22,24,31,32 These reports suggest that recurrence of gland neoplasms after TEL surgical excision or metastatic disease is fairly uncommon.
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The purpose of this study was to describe the various types of neoplasms primarily affecting the TEL gland of dogs and cats. Where follow-up information was available, average survival times, metastatic occurrence, and recurrence rates for each tumor type are reported. METHODS
A retrospective search through the 40 000 case archive of the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) database was performed. Search criteria included primary neoplasms arising from the glandular tissue of the third eyelid in dogs and cats as diagnosed by a board-certified veterinary pathologist (RRD) from formalin-fixed, Hematoxylin and Eosin-stained 5-micron paraffin sections of submitted tissues. Cases in which surface neoplasms secondarily affected TEL gland were excluded as they were not considered primary glandular neoplasms. Veterinary ophthalmologists, primary care veterinarians, and occasionally owners were contacted via phone or email for patient follow-up information. Patient data points collected included species, age, sex, breed, laterality, tumor type, surgical margins, recurrence (confirmed or suspected), metastasis (confirmed or suspected), and length of follow-up. Surgical margins were defined as complete (tissue margins free of neoplastic cells for a distance of greater than 1 mm), narrow (tissue margins free of neoplastic cells for a distance of less than 1 mm), or incomplete (neoplastic cells extend to the cut tissue margin). Metastasis was confirmed when cytologic or histologic evidence of the neoplasm at distant sites within the body occurred. Metastasis was suspected when unidentified
Figure 1. Photomicrograph of feline third eyelid glandular adenocarcinoma. Note the neoplastic epithelial cells forming features of a glandular origin such as acini, ducts, or cytoplasmic features of secretion. Malignancy was indicated by poor differentiation, cellular features of anaplasia, desmoplastic mesenchymal tissue, locally invasive behavior, or vascular invasion. (Hematoxylin and Eosin stain).
masses occurred in distant sites and was not cytologically/ histologically confirmed to be the same neoplasm affecting the TEL. Recurrence was confirmed when neoplastic tissue was noted clinically at the surgical site as diagnosed with cytology or histology. Recurrence was suspected when abnormal tissue was noted at the surgical site but not confirmed to be neoplastic. Length of follow-up was defined as time (days) from surgery to acquisition of information from veterinarians or owners. Log-rank analyses were performed to assess difference in survival times between groups. Cox proportional hazard’s models were used to evaluate association of various factors with overall survival times. Fisher’s exact test was used to determine whether surgical margins were associated with tumor recurrence. Statistical significance was set at P ≤ 0.05. RESULTS
Canine A total of 127 canine cases met the inclusion criteria. The average age of all cases was 10.81 years (range = 3– 16 years). The majority of cases were males [n = 81; 60.9% (90.1% neutered)] as compared to females [n = 46; 34.6% (100% spayed)]. The sex/intact status was not reported in 4.5% of cases. The right TEL was affected in 54 cases (42.5%), the left TEL was affected in 63 cases (48.6%), and laterality was not reported in 10 cases (7.9%). The breed distribution for all cases is listed in Table 1. Mixed-breed dogs (n = 27; 20.2%) were more commonly affected followed by Labrador Retriever (n = 10; 7.5%), Shih Tzu (n = 9; 6.8%), American Cocker Spaniel (n = 9; 6.8%), Dachshund (n = 9; 6.8%), Beagle (n = 8; 6.0%), and Golden Retriever (n = 8; 6.0%). Breed groups with five or less cases included Siberian Husky,
Figure 2. Photomicrograph of canine third eyelid glandular adenoma. Note the neoplastic epithelial cells with features of glandular epithelium and having well-delineated margins. (Hematoxylin and Eosin stain).
© 2015 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 1–6
third eyelid gland neoplasms in dogs and cats 3 Table 1. Canine and feline breed distribution Breed
Figure 3. Photomicrograph of feline third eyelid glandular squamous cell carcinoma. Note the neoplastic stratified squamous epithelial cells infiltrating the glandular tissue, however, having no glandular differentiation. (Hematoxylin and Eosin stain).
Australian Shepherd, Chihuahua, Poodle, Basset Hound, Boston Terrier, Chesapeake Bay Retriever, Lhasa Apso, Alaskan Malamute, Basenji, Bichon Frise, Bloodhound, Bouvier des Flandres, Boxer, Brittany Spaniel, Cairn Terrier, Cavalier King Charles Spaniel, Cockapoo, Dalmatian, English Setter, Field Spaniel, French Bulldog, German Shepherd, Miniature Dachshund, Miniature Poodle, Pembroke Welsh Corgi, Pit Bull Terrier, English Springer Spaniel, Weimaraner, Welsh Corgi, Whippet, and Wirehaired Fox Terrier. All data, including follow-up analysis, are listed in Table 2. The most commonly diagnosed TEL gland neoplasm in dogs was adenocarcinoma (Fig. 1) (n = 108; 85.0%). These tumors were characterized by neoplastic epithelial cells often forming features indicative of a glandular origin such as acini, ducts, or cytoplasmic features of secretion. Malignancy was indicated by poor differentiation, cellular features of anaplasia, desmoplastic mesenchymal tissue, locally invasive behavior, or vascular invasion. Surgical margins were classified as complete (n = 38), narrow (n = 23), incomplete (n = 45), or were not mentioned (n = 2). Follow-up information was available for 54 cases. Metastasis was suspected in five cases (two narrow; three incomplete margins). Local recurrence was confirmed in one case (narrow margins) and suspected in six cases (one narrow; five incomplete margins). The average survival time (AST) for all cases with follow-up available was 670.70 days (range = 14–2738 days). The AST was 769.45 days (range = 51–2738 days) for cases with complete/narrow margins, 438.94 days (range = 14–1825 days) for those with incomplete margins, 747.69 days (range = 51–2738 days) for those with no suspected or confirmed metastasis/recurrence, and 496.83 days (range = 14–2555 days) for those with suspected or confirmed metastasis/recurrence. Statistical analyses found
Canine Mixed breed Labrador retriever American cocker spaniel Dachshund Beagle Golden retriever Siberian husky Australian shepherd Chihuahua Poodle Basset hound Boston terrier Chesapeake bay retriever Lhasa apso Alaskan malamute Basenji Bichon frise Bloodhound Bouvier des flandres Boxer Brittany spaniel Cairn terrier Cavalier king charles spaniel Cockapoo Dalmatian English setter Field spaniel French bulldog German shepherd Miniature dachshund Miniature poodle Pembroke welsh corgi Pit bull terrier English springer spaniel Weimaraner Welsh corgi Whippet Wirehaired fox terrier Feline Domestic shorthair Domestic medium hair Domestic longhair Maine coon Siamese
No. of cases
% of total
27 10 9 9 8 8 5 4 3 3 2 2 2 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
20.2 7.5 6.8 6.8 6.0 6.0 3.8 3.0 2.3 2.3 1.5 1.5 1.5 1.5 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8
14 1 1 1 1
78.0 5.5 5.5 5.5 5.5
no significant difference between the following comparisons: survival times between dogs with TEL adenocarcinoma vs. those with other TEL tumor types (P = 0.5257); survival times between dogs with TEL adenocarcinoma with incomplete surgical margins vs. those with complete/ narrow margins (P = 0.5832); survival times between dogs with suspected metastasis vs. those with no suspected metastasis (P = 0.8171); and survival times between dogs with suspected or confirmed recurrence vs. those without recurrence (P = 0.1047). The difference in survival times between dogs with TEL adenocarcinoma and confirmed or suspected metastasis and those with no confirmed metastasis was statistically significant (P = 0.0135).
© 2015 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 1–6
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Table 2. Third eyelid glandular neoplasms in dogs and cats
Tumor type
No. of cases
No. cases with follow-up
Metastasis* (%)
Recurrence* (%)
AST (days)
Canine Adenocarcinoma Adenoma SCC Feline Adenocarcinoma SCC
127 108 18 1 18 15 3
62 54 8 0 10 8 2
5 (8.1) 5 (9.3) 0 (0) N/A 4 (40.0) 4 (50.0) 0 (0)
7 (11.3) 7 (13.0) 0 (0) N/A 3 (30.0) 2 (25.0) 1 (50.0)
652.80 670.70 532.0 N/A 311.1 334.63 217.0
AST—complete/ narrow margins
AST— incomplete margins
AST—No metastasis or recurrence
AST— metastasis or recurrence
769.45 615.0 N/A
438.94 552.0 N/A
747.69 N/A N/A
496.83 N/A N/A
287.5 N/A
350.33 N/A
313.3 N/A
347.40 N/A
*Data for suspected and confirmed metastasis and local recurrence were combined. AST = average survival time.
The second most common TEL gland tumor of dogs was adenoma (Fig. 2) (n = 18; 14.2%). These tumors were characterized by recognizable features of neoplastic glandular epithelium and well-delineated margins. Surgical margins were classified as complete (n = 8), narrow (n = 3), or incomplete (n = 7). Follow-up information was available for eight cases. The average survival time for all cases with follow-up available was 532.0 days (range = 14–2014 days). The average survival time for cases with complete/narrow margins and incomplete margins was 615.0 days (range = 14–2014 days) and 552.0 days, respectively. The least commonly diagnosed TEL gland tumor of dogs was squamous cell carcinoma (Fig. 3) (n = 1; 0.8%). This tumor was characterized by neoplastic transformation of the gland ductular epithelium extending throughout and destroying glandular tissues yet remaining confined to that structure. Surgical margin was classified as complete. No further follow-up information was available for this case. Comparing all cases with TEL neoplasms, the following factors were not significantly associated with overall survival time: surgical margins (P = 0.434), confirmed or suspected metastasis (P = 0.9271, and confirmed or suspected recurrence (P = 0.1047). Incomplete surgical margins were not associated with tumor recurrence (odds ratio = 0.959; P = 1.0).
Feline A total of 18 feline cases met the inclusion criteria. The average age of all cases was 12.81 years (range = 4– 15.5 years). The majority of cases were males [n = 10; 55.5% (93.2% neutered)] as compared to females [n = 8; 44.5% (89.9% spayed)]. The sex/intact status was not reported for 3.8% of cases. The right TEL was affected in 10 cases (55.5%), and the left was affected in eight cases (44.5%). The most commonly affected breed was domestic shorthair (n = 14; 78%), followed by domestic medium hair (n = 1; 5.5%), domestic longhair (n = 1; 5.5%), Maine Coon (n = 1; 5.5%), and Siamese (n = 1; 5.5%). The most commonly diagnosed TEL gland neoplasm in cats was adenocarcinoma (Fig. 1) (n = 15; 83.3%). These tumors shared histologic features of adenocarcinoma in dogs. Margins were described as complete (n = 7) or incom-
plete (n = 8). Follow-up information was available for a total of eight cases. Metastasis was confirmed in one case (incomplete margins) at the time of surgery and suspected in a further three cases (one complete, two incomplete margins). Local recurrence was confirmed in two cases (one complete, one incomplete). The average survival time for all cases with follow-up available was 334.63 days (range = 9–953 days). The average survival time for cases with complete/narrow margins, incomplete margins, no suspected or confirmed metastasis/recurrence, and with suspected or confirmed metastasis/recurrence was 287.5 days (range = 210– 266 days), 350.33 days (range = 9–365 days), 313.3 days (range = 210–365 days), and 347.40 days (range = 9– 953 days), respectively. The median survival time for cats with TEL adenocarcinoma was not significantly different from those with squamous cell carcinoma (P = 0.8341). The second most common TEL gland neoplasm affecting cats was squamous cell carcinoma (n = 3; 16.7%). These tumors were similar to those described in dogs. The neoplasm was found to be infiltrative into the orbit in two cases. Surgical margins were classified as incomplete in all three cases. Follow-up information was available for two cases. Metastasis was suspected in one case (incomplete margins), and local recurrence was suspected in one separate case (incomplete margins). Average survival time for all cases with squamous cell carcinoma was 217.0 days (range = 62– 372 days). Median survival time for cats with TEL squamous cell carcinoma was not significantly different from those with adenocarcinoma (P = 0.8341). Evaluating all feline cases, the following comparisons were not statistically significant: survival times between cats with TEL gland tumors with incomplete surgical margins vs. those with complete or narrow (P = 0.70); survival times between cats with confirmed metastasis vs. those without confirmed metastasis (P = 0.3562); and survival times between confirmed or suspected recurrence and those with no recurrence (0.1315). DISCUSSION
Many types of neoplasms can affect the eye and adnexal structures in domestic animals. When considering cases
© 2015 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 1–6
third eyelid gland neoplasms in dogs and cats 5
with neoplasia, an evaluation of how the health and longevity of the eye and patient is essential to determine biologic behavior. Third eyelid tumors can be divided into two categories: (i) those that affect the surface tissues and/ or substantia propria and (ii) those that primary affect glandular tissue. Regarding surface/substantia propria tumors in dogs, many have reported overall good cure rates with surgical and/or medical interventions.1,2,5,17,32 However, certain tumors have higher recurrence rates and metastatic potential. Pirie et al. reported a 23.1% recurrence rate of TEL conjunctival hemangiosarcoma as compared to a 3.0% recurrence rate of TEL conjunctival hemangioma.15 Also, Collins et al.34 recorded a 50% recurrence rate of TEL conjunctival melanoma in dogs. There are two reports of melanoma affecting the TEL conjunctiva in cats. A single case report identified widespread metastasis,20 and Schobert et al.9 reported that 4 of 13 cases had local recurrence. Very little has been written describing the biologic behavior of third eyelid gland tumors. Wilcock et al.24 described seven cases of TEL glandular adenocarcinoma in dogs which had a 57.1% recurrence rate and a 14.3% metastatic rate. Schaffer et al.32 described 52 cases of third eyelid tumors in dogs and cats. Collectively, local recurrence and distant metastasis were noted in 17.0% and 6.4% of canine cases, respectively. Metastasis or local recurrence was not noted in any of the feline patients. Newkirk et al.35 described a single feline case of adenocarcinoma affecting the third eyelid which recurred after surgical excision leading to death of the patient. In the past 10 years, the veterinary literature is lacking case series evaluating the various types and biologic behaviors of third eyelid glandular tumors. In this study, we utilized the archives of COPLOW to accumulate data regarding TEL gland tumors in dogs and cats. We identified a total of 147 cases that fit the inclusion criteria. The most common tumor was adenocarcinoma in both dogs and cats. The average survival times were less for feline patients (381.14 days) compared to dogs (670.7 days). Also the metastatic occurrence (canine = 9.3%; feline = 50.0%) and local recurrence rates (canine = 13.0%; feline = 25.0%) were drastically different. With uneven patient numbers, evaluation of this data is challenging; however, it appears that this tumor is more aggressive and leads to a higher mortality rate in feline patients. Within the canine adenocarcinoma group, confirmed metastatic spread of the tumor was significantly associated with decreased survival times suggesting that thorough evaluation of each patient for metastatic disease and early aggressive surgical intervention is warranted. Squamous cell carcinoma was also found in both species arising from the ductular epithelium of the gland. Albeit quite rare, this specific tumor type has yet to be reported in the veterinary literature. Follow-up data revealed no evidence or suspicion for metastasis; however, suspected local recurrence was noted in one feline case (50%). No
information was available for the canine cases. Although the recurrence rate appears significantly high, the case numbers in this study were very low. A larger case series is necessary to more accurately determine the biologic behavior of this uncommon tumor. Adenoma was the second most common TEL glandular tumor in dogs. Compared to adenocarcinoma in the same species, the metastatic occurrence rate (adenoma = 0%; adenocarcinoma = 9.3%) and local recurrence (adenoma = 0%; adenocarcinoma = 13.0%) were less; however, average survival time was shorter in the adenoma group (adenoma = 532.0 days; adenocarcinoma = 670.7 days). Local recurrence and metastasis being more prevalent in the adenocarcinoma group is somewhat expected due to the malignant nature of the tumor; however, the reason for shorter survival time in the benign adenoma group is unknown. Uneven case numbers and percentage of long-term follow-up within tumor groups may have skewed the data results. Evaluating metastatic occurrence and local recurrence rates of all tumors between species has produced interesting results. For all canine cases with follow-up information available, 8.1% had confirmed or suspected metastasis and 11.3% had confirmed or suspected local recurrence of disease. For all feline cases with follow-up information available, 40.0% had confirmed or suspected metastasis and 30.0% had confirmed or suspected local recurrence of disease. This strongly indicates a poorer overall prognosis for feline patients with third eyelid glandular neoplasms as compared to dogs. This is similar to what has been reported for eyelid neoplasms in both species in that most feline neoplasms have malignant potential and canine eyelid neoplasms are typically benign.36 Although the average age at time of diagnosis for the feline cases was approximately 2 years older than the canine cases, it is thought unlikely for the drastic difference in long-term outcome. As with many studies of this type, there are difficulties when performing retrospective histologic studies in veterinary medicine. Obtaining sufficient patient follow-up information can be extremely challenging and frequently requires contacting referring veterinarians and sometimes owners. In the majority of cases, full necropsies were not performed to determine whether the cause of death or severe illness was secondary to the neoplasm in question. Despite these many challenges, we have provided useful information on an uncommon and poorly understood condition. These data can be used to council pet owners, primary care veterinarians, and veterinary ophthalmologists when dealing with third eyelid glandular neoplasms. In conclusion, TEL gland neoplasia is relatively uncommon in veterinary species, especially cats. All feline TEL gland neoplasms diagnosed in this study were malignant. Third eyelid gland adenocarcinoma appears to have significant interspecies difference regarding biologic behavior between dogs and cats.
© 2015 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 1–6
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REFERENCES 1. Milo J, Snead E. A case of ocular canine transmissible venereal tumor. Canadian Veterinary Journal 2014; 55: 1245–1249. 2. Dees DD, MacLaren NE, Teixeira L et al. An unusual case of ocular melanosis and limbal melanocytoma with benign intraorbital extension in a dog. Veterinary Ophthalmology 2013; 16 (Suppl. 1): 117–122. 3. Schnoke AT, Brooks DE, Wilkie DA et al. Extraocular lymphoma in the horse. Veterinary Ophthalmology 2013; 16: 35–42. 4. Labelle AL, Metzler AG, Wilkie DA. Nictitating membrane resection in the horse: a comparison of long-term outcomes using local vs. general anaesthesia. Equine Veterinary Journal 2011; 40: 42–45. 5. Hong IH, Bae SH, Lee SG et al. Mucosa-associated lymphoid tissue lymphoma of the third eyelid conjunctiva in a dog. Veterinary Ophthalmology 2011; 14: 61–65. 6. Mathes RL, Paige Carmichael K, Peroni J et al. Primary lacrimal gland adenocarcinoma of the third eyelid in a horse. Veterinary Ophthalmology 2011; 14: 48–54. 7. Lopes RA, Cardoso TC, Luvizotto MC et al. Occurrence and expression of p53 suppressor gene and c-Myc oncogene in dog eyelid tumors. Veterinary Ophthalmology 2010; 13: 69–75. 8. Perlmann E, da Silva EG, Guedes PM et al. Co-existing squamous cell carcinoma and hemangioma on the ocular surface of a cat. Veterinary Ophthalmology 2010; 13: 63–66. 9. Schobert CS, Labelle P, Dubielzig RR. Feline conjunctival melanoma: histopathological characteristics and clinical outcomes. Veterinary Ophthalmology 2010; 13: 43–46. 10. Payne RJ, Lean MS, Greet TR. Third eyelid resection as a treatment for suspected squamous cell carcinoma in 24 horses. Veterinary Record 2009; 26: 740–743. 11. Perlmann E, Dagli ML, Martins MC et al. Extramedullary plasmacytoma of the third eyelid gland in a dog. Veterinary Ophthalmology 2009; 12: 102–105. 12. Puff C, Herder V, Philipp A et al. Lymphangiosarcoma in the nictitating membrane of a horse. Journal of Veterinary Diagnostic Investigation 2008; 20: 108–110. 13. Gearhart PM, Steficek BA, Petersen-Jones SM. Hemangiosarcoma and squamous cell carcinoma in the third eyelid of a horse. Veterinary Ophthalmology 2007; 10: 121–126. 14. Pirie CG, Dubielzig RR. Feline conjunctival hemangioma and hemangiosarcoma: a retrospective evaluation of eight cases (1993–2004). Veterinary Ophthalmology 2006; 9: 227–231. 15. Pirie CG, Knollinger AM, Thomas CB et al. Canine conjunctival hemangioma and hemangiosarcoma: a retrospective evaluation of 108 cases (1989–2004). Veterinary Ophthalmology 2006; 9: 215–226. 16. Sansom J, Donaldson D, Smith K et al. Haemangiosarcoma involving the third eyelid in the horse: a case series. Equine Veterinary Journal 2006; 38: 277–282. 17. Liapis IK, Genovese L. Hemangiosarcoma of the third eyelid in a dog. Veterinary Ophthalmology 2004; 7: 279–282. 18. Multari D, Vascellari M, Mutinelli F. Hemangiosarcoma of the third eyelid in a cat. Veterinary Ophthalmology 2002; 5: 273–276.
19. Larocca RD. Eosinophilic conjunctivitis, herpes virus, and mast cell tumor of the third eyelid in a cat. Veterinary Ophthalmology 2000; 3: 221–225. 20. Roels S, Ducatelle R. Malignant melanoma of the nictitating membrane in a cat (Felis vulgaris). Journal of Comparative Pathology 1998; 119: 189–193. 21. Rebhun WC, Del Peiro F. Ocular lesions in horses with lymphosarcoma: 21 cases (1977–1997). Journal of the American Veterinary Medical Association 1998; 212: 852–854. 22. Komaromy AM, Ramsey DT, Render JA et al. Primary adenocarcinoma of the gland of the nictitating membrane in a cat. Journal of the American Animal Hospital Association 1997; 33: 333–336. 23. Dugan SJ, Roberts SM, Curtis CR et al. Prognostic factors and survival of horses with ocular/adnexal squamous cell carcinoma: 147 cases (1978–1988). Journal of the American Veterinary Medical Association 1991; 198: 298–303. 24. Wilcock B, Peiffer R Jr. Adenocarcinoma of the gland of the third eyelid in seven dogs. Journal of the American Veterinary Medical Association 1988; 193: 1549–1550. 25. Lavach JD, Snyder SP. Squamous cell carcinoma of the third eyelid in a dog. Journal of the American Veterinary Medical Association 1984; 184: 975–976. 26. Peiffer RL Jr, Duncan J, Terrell T. Hemangioma of the nictitating membrane in a dog. Journal of the American Veterinary Medical Association 1978; 172: 832–833. 27. Buyukmihci N. Fibrosarcoma of the nictitating membrane in a cat. Journal of the American Veterinary Medical Association 1975; 167: 934–935. 28. Gelatt KN, Myers VS Jr, Perman V et al. Conjunctival squamous cell carcinoma in the horse. Journal of the American Veterinary Medical Association 1974; 165: 617–620. 29. Hallstrom M. Mastocytoma in the third eyelid of a dog. Journal of Small Animal Practice 1970; 11: 469–472. 30. Baril C. Basal cell tumour of the third eyelid in a horse. Canadian Veterinary Journal 1973; 14: 66–67. 31. Bondoc A, Izawa T, Hirata S et al. Myoepithelioma of the gland of the third eyelid in a dog. Journal of Comparative Pathology 2014; 151: 186–189. 32. Schaffer EH, Pfleghaar S, Gordon S et al. Malignant nictitating membrane tumors in dogs and cats. Tierarztliche Praxis 1994; 22: 382–391. 33. Stewart RJ, Hill FW, Masztalerz A et al. Treatment of ocular squamous cell carcinomas in cattle with interleukin-2. Veterinary Record 2006; 159: 668–672. 34. Collins BK, Collier LL, Miller MA et al. Biologic behavior and histologic characteristics of canine conjunctival melanoma. Progress in Veterinary and Comparative Ophthalmology 1993; 3: 135–140. 35. Newkirk KM, Rohrbach BW. A retrospective study of eyelid tumors from 43 cats. Veterinary Pathology 2009; 46: 916– 927. 36. Aquino SM. Management of eyelid neoplasms in the dog and cat. Clinical Techniques in Small Animal Practice 2007; 22: 46–54.
© 2015 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 1–6
DOI:10.1111/vop.12273
Third eyelid gland neoplasms of dogs and cats: a retrospective histopathologic study of 145 cases D. Dustin Dees,* Charles S. Schobert,† Richard R. Dubielzig† and Timothy J. Stein‡ *From Eye Care for Animals, 12419 Metric Blvd, Austin, TX 78758, USA; †Comparative Ocular Pathology Laboratory of Wisconsin, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA; and ‡Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA
Address communications to: D. D. Dees Tel.: (512) 335-3937 Fax: (512) 628-9006 e-mail: [email protected]
Abstract Purpose To describe the various types of primary neoplasms affecting the third eyelid (TEL) gland of dogs and cats. Methods A retrospective search of the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) database was performed. Veterinary ophthalmologists, primary care veterinarians, and, when appropriate, owners were contacted for patient follow-up information. Patient data points collected included species, age, sex, breed, laterality, tumor type, surgical margins, recurrence, metastasis, and length of followup. Results A total of 127 canine and 18 feline cases met the inclusion criteria. The most common canine TEL gland tumor was adenocarcinoma (n = 108; 85.0%) followed by adenoma (n = 18; 14.2%) and squamous cell carcinoma (SCC) (n = 1; 0.8%). For canine cases with follow-up information available (n = 62), 8.1% had confirmed or suspected metastasis and 11.3% had confirmed or suspected local recurrence of disease. The most common feline TEL gland tumor was adenocarcinoma (n = 15; 83.3%) followed by SCC (n = 3; 16.7%). For feline cases with follow-up information available (n = 9), 40.0% had confirmed or suspected metastasis and 30.0% had confirmed or suspected local recurrence of disease. Conclusions This study determined that adenocarcinoma was the most common third eyelid gland tumor in both dogs and cats. The overall survival times were less, and metastatic occurrence and recurrence rates appeared to be higher for feline tumors as compared to those diagnosed in dogs. This is the first report of SCC originating from glandular ductular epithelium. Key Words: adenocarcinoma, adenoma, canine, feline, squamous cell carcinoma, third eyelid gland
INTRODUCTION
The third eyelid (TEL) or nictitating membrane is composed of numerous tissue types including conjunctival epithelium, vascular substantia propria, lymphoid tissue, supporting hyaline cartilage, and associated glandular tissue which contributes to lacrimation. Numerous types of TEL neoplasms have been reported in the veterinary literature including transmissible venereal tumor, squamous cell carcinoma, melanocytoma, melanoma, lymphoma, plasmacytoma, hemangioma, hemangiosarcoma, mast cell tumor, and myoepithelioma in dogs; squamous cell carcinoma, hemangioma, © 2015 American College of Veterinary Ophthalmologists
hemangiosarcoma, melanoma, adenocarcinoma, mast cell tumor, and fibrosarcoma in cats; and squamous cell carcinoma, lymphoma, adenocarcinoma, hemangiosarcoma, lymphangiosarcoma, and basal cell tumor in horses.1–34 The majority of these neoplasms originate from the surface tissues (conjunctival and lymphoid tissues) or the stroma of the substantia propria.1,2,4,5,8–10,12–21,23,25,26,28–30,32–34 Those that originate in the TEL gland are less common and include adenocarcinoma, adenoma, plasmacytoma, myoepithelioma, and lymphoma.3,6,11,22,24,31,32 These reports suggest that recurrence of gland neoplasms after TEL surgical excision or metastatic disease is fairly uncommon.
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The purpose of this study was to describe the various types of neoplasms primarily affecting the TEL gland of dogs and cats. Where follow-up information was available, average survival times, metastatic occurrence, and recurrence rates for each tumor type are reported. METHODS
A retrospective search through the 40 000 case archive of the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) database was performed. Search criteria included primary neoplasms arising from the glandular tissue of the third eyelid in dogs and cats as diagnosed by a board-certified veterinary pathologist (RRD) from formalin-fixed, Hematoxylin and Eosin-stained 5-micron paraffin sections of submitted tissues. Cases in which surface neoplasms secondarily affected TEL gland were excluded as they were not considered primary glandular neoplasms. Veterinary ophthalmologists, primary care veterinarians, and occasionally owners were contacted via phone or email for patient follow-up information. Patient data points collected included species, age, sex, breed, laterality, tumor type, surgical margins, recurrence (confirmed or suspected), metastasis (confirmed or suspected), and length of follow-up. Surgical margins were defined as complete (tissue margins free of neoplastic cells for a distance of greater than 1 mm), narrow (tissue margins free of neoplastic cells for a distance of less than 1 mm), or incomplete (neoplastic cells extend to the cut tissue margin). Metastasis was confirmed when cytologic or histologic evidence of the neoplasm at distant sites within the body occurred. Metastasis was suspected when unidentified
Figure 1. Photomicrograph of feline third eyelid glandular adenocarcinoma. Note the neoplastic epithelial cells forming features of a glandular origin such as acini, ducts, or cytoplasmic features of secretion. Malignancy was indicated by poor differentiation, cellular features of anaplasia, desmoplastic mesenchymal tissue, locally invasive behavior, or vascular invasion. (Hematoxylin and Eosin stain).
masses occurred in distant sites and was not cytologically/ histologically confirmed to be the same neoplasm affecting the TEL. Recurrence was confirmed when neoplastic tissue was noted clinically at the surgical site as diagnosed with cytology or histology. Recurrence was suspected when abnormal tissue was noted at the surgical site but not confirmed to be neoplastic. Length of follow-up was defined as time (days) from surgery to acquisition of information from veterinarians or owners. Log-rank analyses were performed to assess difference in survival times between groups. Cox proportional hazard’s models were used to evaluate association of various factors with overall survival times. Fisher’s exact test was used to determine whether surgical margins were associated with tumor recurrence. Statistical significance was set at P ≤ 0.05. RESULTS
Canine A total of 127 canine cases met the inclusion criteria. The average age of all cases was 10.81 years (range = 3– 16 years). The majority of cases were males [n = 81; 60.9% (90.1% neutered)] as compared to females [n = 46; 34.6% (100% spayed)]. The sex/intact status was not reported in 4.5% of cases. The right TEL was affected in 54 cases (42.5%), the left TEL was affected in 63 cases (48.6%), and laterality was not reported in 10 cases (7.9%). The breed distribution for all cases is listed in Table 1. Mixed-breed dogs (n = 27; 20.2%) were more commonly affected followed by Labrador Retriever (n = 10; 7.5%), Shih Tzu (n = 9; 6.8%), American Cocker Spaniel (n = 9; 6.8%), Dachshund (n = 9; 6.8%), Beagle (n = 8; 6.0%), and Golden Retriever (n = 8; 6.0%). Breed groups with five or less cases included Siberian Husky,
Figure 2. Photomicrograph of canine third eyelid glandular adenoma. Note the neoplastic epithelial cells with features of glandular epithelium and having well-delineated margins. (Hematoxylin and Eosin stain).
© 2015 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 1–6
third eyelid gland neoplasms in dogs and cats 3 Table 1. Canine and feline breed distribution Breed
Figure 3. Photomicrograph of feline third eyelid glandular squamous cell carcinoma. Note the neoplastic stratified squamous epithelial cells infiltrating the glandular tissue, however, having no glandular differentiation. (Hematoxylin and Eosin stain).
Australian Shepherd, Chihuahua, Poodle, Basset Hound, Boston Terrier, Chesapeake Bay Retriever, Lhasa Apso, Alaskan Malamute, Basenji, Bichon Frise, Bloodhound, Bouvier des Flandres, Boxer, Brittany Spaniel, Cairn Terrier, Cavalier King Charles Spaniel, Cockapoo, Dalmatian, English Setter, Field Spaniel, French Bulldog, German Shepherd, Miniature Dachshund, Miniature Poodle, Pembroke Welsh Corgi, Pit Bull Terrier, English Springer Spaniel, Weimaraner, Welsh Corgi, Whippet, and Wirehaired Fox Terrier. All data, including follow-up analysis, are listed in Table 2. The most commonly diagnosed TEL gland neoplasm in dogs was adenocarcinoma (Fig. 1) (n = 108; 85.0%). These tumors were characterized by neoplastic epithelial cells often forming features indicative of a glandular origin such as acini, ducts, or cytoplasmic features of secretion. Malignancy was indicated by poor differentiation, cellular features of anaplasia, desmoplastic mesenchymal tissue, locally invasive behavior, or vascular invasion. Surgical margins were classified as complete (n = 38), narrow (n = 23), incomplete (n = 45), or were not mentioned (n = 2). Follow-up information was available for 54 cases. Metastasis was suspected in five cases (two narrow; three incomplete margins). Local recurrence was confirmed in one case (narrow margins) and suspected in six cases (one narrow; five incomplete margins). The average survival time (AST) for all cases with follow-up available was 670.70 days (range = 14–2738 days). The AST was 769.45 days (range = 51–2738 days) for cases with complete/narrow margins, 438.94 days (range = 14–1825 days) for those with incomplete margins, 747.69 days (range = 51–2738 days) for those with no suspected or confirmed metastasis/recurrence, and 496.83 days (range = 14–2555 days) for those with suspected or confirmed metastasis/recurrence. Statistical analyses found
Canine Mixed breed Labrador retriever American cocker spaniel Dachshund Beagle Golden retriever Siberian husky Australian shepherd Chihuahua Poodle Basset hound Boston terrier Chesapeake bay retriever Lhasa apso Alaskan malamute Basenji Bichon frise Bloodhound Bouvier des flandres Boxer Brittany spaniel Cairn terrier Cavalier king charles spaniel Cockapoo Dalmatian English setter Field spaniel French bulldog German shepherd Miniature dachshund Miniature poodle Pembroke welsh corgi Pit bull terrier English springer spaniel Weimaraner Welsh corgi Whippet Wirehaired fox terrier Feline Domestic shorthair Domestic medium hair Domestic longhair Maine coon Siamese
No. of cases
% of total
27 10 9 9 8 8 5 4 3 3 2 2 2 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
20.2 7.5 6.8 6.8 6.0 6.0 3.8 3.0 2.3 2.3 1.5 1.5 1.5 1.5 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8
14 1 1 1 1
78.0 5.5 5.5 5.5 5.5
no significant difference between the following comparisons: survival times between dogs with TEL adenocarcinoma vs. those with other TEL tumor types (P = 0.5257); survival times between dogs with TEL adenocarcinoma with incomplete surgical margins vs. those with complete/ narrow margins (P = 0.5832); survival times between dogs with suspected metastasis vs. those with no suspected metastasis (P = 0.8171); and survival times between dogs with suspected or confirmed recurrence vs. those without recurrence (P = 0.1047). The difference in survival times between dogs with TEL adenocarcinoma and confirmed or suspected metastasis and those with no confirmed metastasis was statistically significant (P = 0.0135).
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Table 2. Third eyelid glandular neoplasms in dogs and cats
Tumor type
No. of cases
No. cases with follow-up
Metastasis* (%)
Recurrence* (%)
AST (days)
Canine Adenocarcinoma Adenoma SCC Feline Adenocarcinoma SCC
127 108 18 1 18 15 3
62 54 8 0 10 8 2
5 (8.1) 5 (9.3) 0 (0) N/A 4 (40.0) 4 (50.0) 0 (0)
7 (11.3) 7 (13.0) 0 (0) N/A 3 (30.0) 2 (25.0) 1 (50.0)
652.80 670.70 532.0 N/A 311.1 334.63 217.0
AST—complete/ narrow margins
AST— incomplete margins
AST—No metastasis or recurrence
AST— metastasis or recurrence
769.45 615.0 N/A
438.94 552.0 N/A
747.69 N/A N/A
496.83 N/A N/A
287.5 N/A
350.33 N/A
313.3 N/A
347.40 N/A
*Data for suspected and confirmed metastasis and local recurrence were combined. AST = average survival time.
The second most common TEL gland tumor of dogs was adenoma (Fig. 2) (n = 18; 14.2%). These tumors were characterized by recognizable features of neoplastic glandular epithelium and well-delineated margins. Surgical margins were classified as complete (n = 8), narrow (n = 3), or incomplete (n = 7). Follow-up information was available for eight cases. The average survival time for all cases with follow-up available was 532.0 days (range = 14–2014 days). The average survival time for cases with complete/narrow margins and incomplete margins was 615.0 days (range = 14–2014 days) and 552.0 days, respectively. The least commonly diagnosed TEL gland tumor of dogs was squamous cell carcinoma (Fig. 3) (n = 1; 0.8%). This tumor was characterized by neoplastic transformation of the gland ductular epithelium extending throughout and destroying glandular tissues yet remaining confined to that structure. Surgical margin was classified as complete. No further follow-up information was available for this case. Comparing all cases with TEL neoplasms, the following factors were not significantly associated with overall survival time: surgical margins (P = 0.434), confirmed or suspected metastasis (P = 0.9271, and confirmed or suspected recurrence (P = 0.1047). Incomplete surgical margins were not associated with tumor recurrence (odds ratio = 0.959; P = 1.0).
Feline A total of 18 feline cases met the inclusion criteria. The average age of all cases was 12.81 years (range = 4– 15.5 years). The majority of cases were males [n = 10; 55.5% (93.2% neutered)] as compared to females [n = 8; 44.5% (89.9% spayed)]. The sex/intact status was not reported for 3.8% of cases. The right TEL was affected in 10 cases (55.5%), and the left was affected in eight cases (44.5%). The most commonly affected breed was domestic shorthair (n = 14; 78%), followed by domestic medium hair (n = 1; 5.5%), domestic longhair (n = 1; 5.5%), Maine Coon (n = 1; 5.5%), and Siamese (n = 1; 5.5%). The most commonly diagnosed TEL gland neoplasm in cats was adenocarcinoma (Fig. 1) (n = 15; 83.3%). These tumors shared histologic features of adenocarcinoma in dogs. Margins were described as complete (n = 7) or incom-
plete (n = 8). Follow-up information was available for a total of eight cases. Metastasis was confirmed in one case (incomplete margins) at the time of surgery and suspected in a further three cases (one complete, two incomplete margins). Local recurrence was confirmed in two cases (one complete, one incomplete). The average survival time for all cases with follow-up available was 334.63 days (range = 9–953 days). The average survival time for cases with complete/narrow margins, incomplete margins, no suspected or confirmed metastasis/recurrence, and with suspected or confirmed metastasis/recurrence was 287.5 days (range = 210– 266 days), 350.33 days (range = 9–365 days), 313.3 days (range = 210–365 days), and 347.40 days (range = 9– 953 days), respectively. The median survival time for cats with TEL adenocarcinoma was not significantly different from those with squamous cell carcinoma (P = 0.8341). The second most common TEL gland neoplasm affecting cats was squamous cell carcinoma (n = 3; 16.7%). These tumors were similar to those described in dogs. The neoplasm was found to be infiltrative into the orbit in two cases. Surgical margins were classified as incomplete in all three cases. Follow-up information was available for two cases. Metastasis was suspected in one case (incomplete margins), and local recurrence was suspected in one separate case (incomplete margins). Average survival time for all cases with squamous cell carcinoma was 217.0 days (range = 62– 372 days). Median survival time for cats with TEL squamous cell carcinoma was not significantly different from those with adenocarcinoma (P = 0.8341). Evaluating all feline cases, the following comparisons were not statistically significant: survival times between cats with TEL gland tumors with incomplete surgical margins vs. those with complete or narrow (P = 0.70); survival times between cats with confirmed metastasis vs. those without confirmed metastasis (P = 0.3562); and survival times between confirmed or suspected recurrence and those with no recurrence (0.1315). DISCUSSION
Many types of neoplasms can affect the eye and adnexal structures in domestic animals. When considering cases
© 2015 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 1–6
third eyelid gland neoplasms in dogs and cats 5
with neoplasia, an evaluation of how the health and longevity of the eye and patient is essential to determine biologic behavior. Third eyelid tumors can be divided into two categories: (i) those that affect the surface tissues and/ or substantia propria and (ii) those that primary affect glandular tissue. Regarding surface/substantia propria tumors in dogs, many have reported overall good cure rates with surgical and/or medical interventions.1,2,5,17,32 However, certain tumors have higher recurrence rates and metastatic potential. Pirie et al. reported a 23.1% recurrence rate of TEL conjunctival hemangiosarcoma as compared to a 3.0% recurrence rate of TEL conjunctival hemangioma.15 Also, Collins et al.34 recorded a 50% recurrence rate of TEL conjunctival melanoma in dogs. There are two reports of melanoma affecting the TEL conjunctiva in cats. A single case report identified widespread metastasis,20 and Schobert et al.9 reported that 4 of 13 cases had local recurrence. Very little has been written describing the biologic behavior of third eyelid gland tumors. Wilcock et al.24 described seven cases of TEL glandular adenocarcinoma in dogs which had a 57.1% recurrence rate and a 14.3% metastatic rate. Schaffer et al.32 described 52 cases of third eyelid tumors in dogs and cats. Collectively, local recurrence and distant metastasis were noted in 17.0% and 6.4% of canine cases, respectively. Metastasis or local recurrence was not noted in any of the feline patients. Newkirk et al.35 described a single feline case of adenocarcinoma affecting the third eyelid which recurred after surgical excision leading to death of the patient. In the past 10 years, the veterinary literature is lacking case series evaluating the various types and biologic behaviors of third eyelid glandular tumors. In this study, we utilized the archives of COPLOW to accumulate data regarding TEL gland tumors in dogs and cats. We identified a total of 147 cases that fit the inclusion criteria. The most common tumor was adenocarcinoma in both dogs and cats. The average survival times were less for feline patients (381.14 days) compared to dogs (670.7 days). Also the metastatic occurrence (canine = 9.3%; feline = 50.0%) and local recurrence rates (canine = 13.0%; feline = 25.0%) were drastically different. With uneven patient numbers, evaluation of this data is challenging; however, it appears that this tumor is more aggressive and leads to a higher mortality rate in feline patients. Within the canine adenocarcinoma group, confirmed metastatic spread of the tumor was significantly associated with decreased survival times suggesting that thorough evaluation of each patient for metastatic disease and early aggressive surgical intervention is warranted. Squamous cell carcinoma was also found in both species arising from the ductular epithelium of the gland. Albeit quite rare, this specific tumor type has yet to be reported in the veterinary literature. Follow-up data revealed no evidence or suspicion for metastasis; however, suspected local recurrence was noted in one feline case (50%). No
information was available for the canine cases. Although the recurrence rate appears significantly high, the case numbers in this study were very low. A larger case series is necessary to more accurately determine the biologic behavior of this uncommon tumor. Adenoma was the second most common TEL glandular tumor in dogs. Compared to adenocarcinoma in the same species, the metastatic occurrence rate (adenoma = 0%; adenocarcinoma = 9.3%) and local recurrence (adenoma = 0%; adenocarcinoma = 13.0%) were less; however, average survival time was shorter in the adenoma group (adenoma = 532.0 days; adenocarcinoma = 670.7 days). Local recurrence and metastasis being more prevalent in the adenocarcinoma group is somewhat expected due to the malignant nature of the tumor; however, the reason for shorter survival time in the benign adenoma group is unknown. Uneven case numbers and percentage of long-term follow-up within tumor groups may have skewed the data results. Evaluating metastatic occurrence and local recurrence rates of all tumors between species has produced interesting results. For all canine cases with follow-up information available, 8.1% had confirmed or suspected metastasis and 11.3% had confirmed or suspected local recurrence of disease. For all feline cases with follow-up information available, 40.0% had confirmed or suspected metastasis and 30.0% had confirmed or suspected local recurrence of disease. This strongly indicates a poorer overall prognosis for feline patients with third eyelid glandular neoplasms as compared to dogs. This is similar to what has been reported for eyelid neoplasms in both species in that most feline neoplasms have malignant potential and canine eyelid neoplasms are typically benign.36 Although the average age at time of diagnosis for the feline cases was approximately 2 years older than the canine cases, it is thought unlikely for the drastic difference in long-term outcome. As with many studies of this type, there are difficulties when performing retrospective histologic studies in veterinary medicine. Obtaining sufficient patient follow-up information can be extremely challenging and frequently requires contacting referring veterinarians and sometimes owners. In the majority of cases, full necropsies were not performed to determine whether the cause of death or severe illness was secondary to the neoplasm in question. Despite these many challenges, we have provided useful information on an uncommon and poorly understood condition. These data can be used to council pet owners, primary care veterinarians, and veterinary ophthalmologists when dealing with third eyelid glandular neoplasms. In conclusion, TEL gland neoplasia is relatively uncommon in veterinary species, especially cats. All feline TEL gland neoplasms diagnosed in this study were malignant. Third eyelid gland adenocarcinoma appears to have significant interspecies difference regarding biologic behavior between dogs and cats.
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