Anterior orbital and eyelid swelling for 1 y. Right eye exophthalmos and 3rd eyelid prolapse; mucopurulent discharge and phthisis bulbi; periorbital swelling and.
ARTICLES
Equine orbital neoplasia: A review of 10 cases
(1983-1998)
Keith E. Baptiste, Bruce H. Grahn Abstract - The clinical manifestations, laboratory findings, and survival times of 10 horses with orbital neoplasms are reported. In all cases, orbital neoplasms were malignant and locally invasive with no defined surgical circumscribed edges. It was often difficult to identify the primary cell type of the neoplasia in histologic specimens due to the poorly differentiated, anaplastic nature of the majority of cases. All except one horse were eventually euthanized 2 mo to 5 y after diagnosis due to poor response to treatment, metastasis, or unrelenting orbital neoplasia. Mean survival time increased with surgical treatment, but no significant difference was found among no treatment, chemotherapy, surgical mass removal, or exenteration/enucleation. Equine practitioners should be aware of the marked difference in prognosis of orbital neoplasms compared with ocular or localized eyelid neoplasia.
Resume - Neoplasie orbitaire equine: analyse de 10 observations (1983-1998). Les manifestations cliniques, les donnees de laboratoire et les temps de survie observes chez 10 chevaux presentant des neoplasmes orbitaires sont rapportes. Dans tous les cas, les neoplasmes orbitaires etaient malins, localement invasifs et sans contours chirurgicaux definis. I1 etait souvent difficile d'identifier a l'histologie le type cellulaire primaire du neoplasme a cause de la nature peu differenciee et anaplasique de la majorite des cas. A l'exception d'un, tous les chevaux ont ete eventuellement euthanasies entre 2 mois et 5 ans apres le diagnostic suite soit a un faible reponse au traitement, soit a des metastases ou encore a une neoplasie sans remission. Le temps moyen de survie a augmente suite au traitement chirurgical mais il n'y avait pas de difference significatice entre les non-traites, ceux ayant subi un chimiotherapie, une ablation chirurgicale de la masse ou une exenteration/ enucleation. Les praticiens equins devraient etre au courant de la difference marquee dans le pronostic des neoplasmes orbitaires et des neoplasies oculaires ou palpebrales localisees. (Traduit par docteur Andre' Blouin) Can Vet J 2000;41:291-295
Introduction O rbital neoplasia in the horse is uncommon (1). These neoplasms can be either primary, arising from orbital tissues (neuroendocrine) (2), or metastatic, invading the orbit by local extension from adjacent tissues (squamous cell carcinoma, SCC) (1) or via the vascular system (lymphosarcoma, angiosarcoma) (3,4). The clinical manifestations of orbital neoplasia include nonpainful progressive exophthalmos (1) or, occasionally, enophthalmos; congestion and swelling of the conjunctival and episcleral tissues; as well as third eyelid prolapse. However, these clinical signs are not specific for orbital neoplasia. Inflammatory conditions, including abscess/cellulitis; granuloma; edema and hemorrhage, secondary to trauma; cystic anomalies related to congenital abnormalities; parasitic or nonneoplastic diseases extending from periorbital regions (1); and guttural pouch mycosis (5), must also be considered as differential diagnoses. Department of Veterinary Internal Medicine, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4. Address correspondence and reprint requests to Dr. Bruce Grahn. Can Vet J Volume 41, April 2000
Most of the primary and metastatic orbital neoplasms are malignant and associated with a poor prognosis (6). However, Basher et al (2) report that equine neuroendocrine orbital neoplasms without neurologic signs that are treated with orbital exenteration may have a better long-term survival than most orbital neoplasms. Other reported orbital neoplasms in the horse include hemangiosarcoma, hemangioma, mast cell tumor, lipoma, undifferentiated adenocarcinoma, and metastatic
lymphosarcoma (3). Local extension from adjacent tissue is the most common form of metastatic orbital neoplasia (1). These tend to be malignant neoplasms with a poor prognosis (1). The exception is a benign retrobulbar melanoma reported in a 16-year-old grey mare (7). We reviewed the veterinary literature from 1970-1998 using computer databases (Agricola, CAB abstracts, Medline Express). Descriptions of equine orbital neoplasia were limited to individual case reports (2,8-12), and a case series including ocular, orbital, and adnexal neoplasia (4). The objectives of this retrospective study were to document the clinical manifestations, laboratory findings, and survival time with or without medical and surgical therapy of varied orbital neoplasms in the horse. 291
Table 1. Summary of clinical and laboratory findings in 10 cases of equine orbital neoplasia Signalment
1
Clinical and laboratory findings
History
Histopathology
Biopsy: malignant
Treatment and outcome
Treatment: surgical mass resection; 2x cryotherapy; 3x BNP, BCG, phenylbutazone Outcome: euthanized 36 wk after progressive orbital disease PM: anaplastic SCC with metastasis
American 2-3 cm diameter mass in quarter horse left lower anterior 11 y; gelding orbit and eyelid, present for 6 mo
Flat, round, hairless mass;
2
Thoroughbred Blind in right eye, less 22 y; gelding vision in left eye for 8 mo; head trauma 2 wk previous, epistaxis from right nostril
Bilateral exophthalmos and 3rd eyelid prolapse; bilateral uveitis with edematous, bulging conjunctival membranes; left and right anterior chambers filled with opaque protein-rich material
3
Clydesdale 5 y; mare
Right eye punctured as a foal
Right eye exophthalmos Biopsy: poorly and 3rd eyelid prolapse; differentiated SCC mucopurulent discharge and phthisis bulbi; periorbital swelling and edema. mass between right ventral and middle nasal turbinates
Treatment: enucleation Outcome: euthanized 8 wk after initial signs due to poor response to Tx
4
Appaloosa 5 y; gelding
Foreign body in eye 8 mo previous
Exophthalmos and 3rd eyelid prolapse; orbital mass with upper eyelid involvement
Treatment: enucleation mass adhered to periosteum of orbit Outcome: similar mass developed in other eye; euthanized 52 wk after initial clinical signs
5
American
Anterior orbital and eyelid swelling for 1
quarter horse
y
17 y; gelding
6
7
Clydesdale 13 y; mare
American paint horse 9 y; mare
Mass on left medial bulbar of eye extending into cornea
Swollen left lower anterior orbit for
10
d
enlarged submandibular lymph node
KIF = positive VIF = negative Diagnosis at PM
Biopsy: anaplastic SCC
Treatment: None Outcome: euthanized 32 wk after initial signs PM: infiltrative adenocarcinoma involving posterior orbit, ethmoid, cribriform plate, sphenopalatine and frontal sinuses
Two masses infiltrating Biopsy: poorly differentiated SCC upper and lower eyelids. Eye is visual, and enophthalmic
Treatment: surgical mass resection; orbital neoplasia recurred 2 y later; eye remained visual; no further Tx Outcome: euthanized 5 y after initial signs
Exophthalmos and 3rd eyelid prolapse; mass infiltrating lateral limbus, cornea, sclera and extends into retrobulbar area; bilateral, posterior capsular cataracts
Treatment: surgical mass resection. Mass regrew in 1 y, then enucleated Outcome: euthanized 4 y after initial signs PM: 2 neoplastic processes; systemic lymphosarcoma; anaplastic neoplasia of left orbit, temporal fossa, nasolacrimal duct and left paranasal region
Biopsy#1: SCC Biopsy#2: poorly differentiated, mesenchymal spindle cell neoplasm KIF = negative VIF = positive T-CD3 = negative FVIII = positive
Exophthalmos and Biopsy: poorly differentiated 3rd eyelid prolapse; mesenchymal painful swollen left lower eyelid, neoplasia mucopurulent discharge, KIF = negative conjunctivitis, severe VIF = positive chemosis with corneal T-CD3 = negative edema; enlarged submandibular lymph MHC2 = negative node FVIII = positive
Materials and methods The medical records of horses with orbital disease from the Western College of Veterinary Medicine (WCVM) were reviewed and compared for the period of 1983 to 1998. For the purposes of this study, a horse had an 292
anaplastic neoplasia
Treatment: 3x Tx intralesional cisplatin in sesame oil, IM penicillin. Poor response Outcome: euthanized 10 wk after clinical signs due to poor response PM: undifferentiated anaplastic neoplasia with local metastasis
orbital neoplasm when all of the following criteria were met: an orbital mass causing progressive ocular displacement and light microscopic evidence of neoplasia from biopsy or post mortem examination. All cases had been followed for a minimum of 12 mo or until the case was considered resolved. A statistical analysis Can Vet J Volume 41, April 2000
Table 1. (concluded) Signalment 8
Pinto 19 y; mare
History
Clinical and laboratory findings
Noticed tearing and Exophthalmos and growth over right upper 3rd eyelid prolapse; anterior orbit 1 y mucopurulent ocular previous; seemed to get discharge; large, smaller but had painful subconjunctival worsened over last mass extending into month right anterior orbit and upper eyelid; cornea infiltrated and
Histopathology
Treatment and outcome
Biopsy: inconclusive anaplastic sarcoma
Treatment: none Cornea eventually became totally opaque, phthisis bulbi and blindness developed Outcome: euthanized for humane reasons 72 wk after initial signs
Biopsy: anaplastic carcinoma
Treatment: none Outcome: alive and doing well 52 wk after diagnosis
neovascularized; bilateral posterior central cataracts
9
Belgian 9 y; gelding
SCC involving both eyes; enucleated right eye due to severity
10
Appaloosa 9 y; mare
Mass present on right Mucopurulent ocular lower anterior orbit and discharge, mild eyelid; surgically blepharospasm; removed and recurred thickening of 4 mo later dorsolateral canthus and ulceration of lower eyelid with thickening
Orbital swelling in left eye; exophthalmos and 3rd eyelid prolapse
Biopsy: mesenchymal Treatment: none; progressive spindle cell neoplasia orbital swelling to the point the horse could not open eyelids anymore Outcome: Euthanized 36 wk after initial signs
SCC - Squamous cell carcinoma; PM - Post mortem; Tx - Treatment; KIF - Keratin intermediate filament; VIF - Vimentin intermediate filament; T-CD3T-lymphocyte CD3 marker; MHC2 - Class 2 major histocompatibility complex marker; FVIH -Factor VHI-related antigen; BCG -Bacille Calmette-Gu6rin; BNPBacitracin, neomycin and polymyxin B
was performed, comparing treatments with survival times by using a Kruskal-Wallis, one-way nonparametric, analysis of variance test.
Results During the period of study, 10 horses had been confirmed to have orbital neoplasms (Table 1). The horses ranged in age from 5 y to 22 y (mean age, 12 y). There appeared to be no breed or sex predilection. All except one horse were eventually euthanized 2 mo to 5 y after the diagnosis, due to poor response to treatment, metastasis, or progressive unrelenting orbital neoplasia (Table 1). The clinical manifestations of orbital neoplasia in these cases are summarized in Table 1. In general, horses presented with exophthalmos, third eyelid prolapse
and conjunctival swelling, and, sometimes, uveitis (Figure 1). In all cases, the orbital neoplasms were malignant and locally invasive with no defined surgical circumscribed edges. In some cases, these neoplasms had initially been confused clinically as sarcoids, conjunctival SCC, or trauma. Histologic specimens were often difficult to interpret due to the bizarre cellular characteristics. The light microscopic diagnosis in this series of neoplasms included anaplastic sarcoma (n = 5) (Figure 2), poorly differentiated SCC (n = 4) (Figure 3), and adenocarcinoma (n = 1). Two of the mesenchymal neoplasms could only be defined as poorly differentiated anaplastic spindle cell tumors, despite the use of immunohistochemical techniques. This was not unexpected, given the limited cellular differentiation of these neoplasms and the lack of equine specific cell markers available. The horses in this study were either treated by chemotherapy (n = 2), surgical mass resection (n = 3), exenteration/enucleation (n = 3), or left untreated (n = 4) Can Vet J Volume 41, April 2000
Figure 1. Photograph of a horse with an orbital tumor (Case #7). Note the exophthalmos and severe conjunctival
swelling. 293
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Figure 2. Light microscopy picture of hematoxylin-eosin-stained section from a anaplastic mesenchymal neoplasm found in this series of horses; bar = 40 ,um.
Figure 3. Light microscopy picture of hematoxylin-eosinstained section from a poorly differentiated squamous cell carcinoma found in this series of horses; bar = 40 pm.
(Table 1). Horses that were left untreated had a mean survival time of 11 mo. The mean survival time with exenteration/enucleation was 16.7 mo, and with chemotherapy, 6 mo. Combination treatments (chemotherapy and mass resection) did not change mean survival times. Statistical analysis showed no significant difference in mean survival time among no treatment, chemotherapy, surgical mass removal, or exenteration/enucleation.
Discussion The clinical manifestations of orbital neoplasia in these cases included persistent third eyelid prolapse; progressive conjunctival and eyelid swelling; and exophthalmos. These findings were consistent with previous reports (1). Although neoplasms of the equine orbit are relatively rare and the number of cases in this study is small, several important observations are apparent. Several basic principles of orbital neoplasia therapy were violated. This is not unexpected, given the time span of the retrospective case series and the morphologic characteristics of these neoplasms. Most of these neoplasms (n = 7) were not staged (area involved or metastasis) at the time of the initial therapy. Lymph node aspirates, thoracic radiographs, hematology, and serum chemistry profiles may have confirmed metastasis in these 294
cases at that time. A complete physical and orbital examination with retropulsion of the globe, and ancillary tests, including orbital ultrasound, skull radiographs, and fine needle aspiration or biopsy, were often lacking (n = 6). Several of the tumors (n = 4) were not accurately diagnosed at the time of selection of the initial therapy. Eyelid involvement at the time of initial examination tended to influence the diagnosis as a benign or localized growth (SCC, sarcoid). Even when biopsies were taken, identification of the cell of origin of the neoplasm with light microscopy was often difficult, and misdiagnosis did occur (n = 4). In some cases, this was due to the small amount of neoplastic tissue in the biopsy submitted and, in others, the neoplastic cells were poorly differentiated and very difficult to identify. Immunohistochemical tests (nonspecific esterase, fluoride, keratin and vimentin intermediate filament, s-100, major histocompatibility complex-2 antigen, T-lymphocyte CD3 antigen, factor VIII-related antigen) were performed on 2 of these neoplasms in an attempt to determine the cell line of origin. Results were equivocal. In some cases, a review of the initial and subsequent biopsies when these neoplasms recurred resulted in a new diagnosis (n = 4). This occurred because subsequent biopsies had an increased amount of neoplastic tissue, allowing for a more complete assessment. The surgical therapy of choice for orbital neoplasia is exenteration early in the course of the disease (6). This surgical procedure removes the entire orbital content. Unfortunately, exenteration was not likely completed in 3 cases, as several surgeons treated these cases and a review of surgical records eluded that complete removal of all orbital tissue was unlikely. Thorough exenteration might have lengthened the survival time in these cases, if there were no metastases at the time of the surgeries. Chemotherapy was attempted in 2 cases by using Bacille Calmette-Guerin (BCG) or cisplatin. Cisplatin has been successfully used intralesionally in periocular sarcoids and SCC in horses (13). These agents were unsuccessful at controlling the neoplastic growth or in extending the survival time of these 2 horses compared with others in this study. This may have been the result of many factors, including the type and stage of the neoplasm at the time of therapy, the chemotherapeutic agent, and the difficulty of injecting the drug into all parts of the tumor. The prognosis for survival in the cases in this series was poor and all, except one horse, were eventually euthanized due to progressive, unrelenting orbital disease, regardless of the method of therapy. However, given the low number of cases and other confounding variables (tumor type, stage of development, client economics), it is difficult to truly determine if there was a statistical difference in survival based on treatments. A larger, prospective study is necessary to determine the effect of treatment on survival times. The most common tumors of the equine eye and adnexa include sarcoids and SCC (1). A good prognosis (> 80%) is possible with early treatment (14). In one case series (14), orbital SCC was associated with the poorest prognosis, with a mean survival time of 9 mo. Our review has confirmed that equine orbital neoplasms Can Vet J Volume 41, April 2000
are usually malignant, when compared with most neoplasms of the eye. Retrospective studies on orbital neoplasia in the dog have revealed similar findings. The prognosis is poor, regardless of the therapy; the survival rate beyond 12 mo was less than 10% (15,16). Similarly, in humans, the mean survival time for metastatic orbital tumors was 10.2 mo (17). Equine practitioners should be aware of the marked difference in prognosis of orbital neoplasms compared with ocular or localized eyelid neoplasia. Clinicians who treat orbital neoplasia in the horse should accurately diagnose, stage the neoplasm, and then choose an appropriate therapy for each individual case. Exenteration is currently the surgical therapy of choice. If the clinical manifestations are recognized early and thorough pretreatment investigation and diagnosis are completed, an improved prognosis may result.
Acknowledgments The authors thank Drs. Fretz, Barber, and Scott, members of the WCVM Pathology Department who worked on some of these cases. cv.
References 1. Dugan SJ. Ocular neoplasia. Vet Clin North Am Equine Pract
1992;8:609-626. 2. Basher AWP, Severin GA, Chavkin MJ, Frank AA. Orbital neuroendocrine tumors in three horses. J Am Vet Med Assoc 1997;210:668-67 1. 3. Hacker DV, Moore PF, Buyukmihci NC. Ocular angiosarcoma in four horses. J Am Vet Med Assoc 1986;189:200-203.
4. Lavach JD, Severin GA. Neoplasia of the eye, adnexa, and orbit: A review of 68 cases. J Am Vet Med Assoc 1977;170:202-203. 5. Lavach SD. The Handbook of Equine Ophthalmology. Colorado: Giddings Studio Publ, 1977:35 1. 6. Davidson MG. Equine ophthalmology. In: Gelatt KN, ed. Veterinary Ophthalmology. 2nd ed. Philadelphia: Lea & Febiger, 1991:576-610. 7. Sweeney CR, Beech J. Retrobulbar melanoma in a horse. Equine Vet J 1983;Suppl 2:123-124. 8. Bistner S, Campbell J, Shaw D, Leininger JR, Ghobrial HK. Neuroepithelial tumor of the optic nerve in a horse. Cornell Vet 1983;73:30-40. 9. Freestone JF, Glaze MB, Pechman R, McClure JR. Ultrasonic identification of an orbital neoplasia in a horse. Equine Vet J 1989; 21: 135-136. 10. Koch DB, Leitch M, Beech J. Orbital surgery in two horses. Vet Surg 1980;9:61-65. 11. Rebhun WC, Del Piero F. Ocular lesions in horses with lymphosarcoma: 21 cases (1977-1997). J Am Vet Med Assoc 1998; 212:852-854. 12. Richardson DW, Acland HM. Multilobular osteoma (chondroma rodens) in a horse. J Am Vet Med Assoc 1983;182:289-291. 13. Theon AP, Pascoe JR, Madigan JE, Carlson G, Metzger L. Comparison of intratumoral administration of cisplatin versus bleomycin for treatment of periocular squamous cell carcinomas in horses. Am J Vet Res 1997;58:431-436. 14. Dugan SJ, Roberts SM, Curtis CR, Severin GA. Prognostic factors and survival of horses with ocular/adnexal squamous cell carcinoma: 147 cases (1978-1988). J Am Vet Med Assoc 1991;198: 298-303. 15. Gross S, Aguirre G, Harvey C. Tumors involving the orbit of the dog. Proc 10th Am Coll Vet Ophthalmol 1979:229-240. 16. Kern TJ. Orbital neoplasia in 23 dogs. J Am Vet Med Assoc 1985;186:489-491. 17. Goldberg RA, Rootman J. Clinical characteristics of metastatic orbital tumors. Ophthalmology 1990;97:620-624.
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