History

A 13-year-old 412-kg (906-lb) bay Arabian gelding was presented to the ophthalmology service of a veterinary teaching hospital for evaluation of its right eye, which appeared to be painful according to the owner. The horse had shown signs of blepharospasm and epiphora for 2 months before referral.

Clinical and Gross Findings

The horse was sedated, and a complete ophthalmic examination of the right eye revealed diminished vision (negative menace response and direct pupillary light reflex and positive dazzle response and consensual pupillary light reflex), buphthalmia, a complicated superficial corneal ulceration, severe uveitis with 3+ aqueous flare (flare scale, trace to 4+), an irregular hyperpigmented iris with multifocal areas of depigmentation, yellow discoloration of the iris, and secondary glaucoma (Figure 1) Intraocular pressure (IOP) in the right eye was 34 mm Hg (typical range for IOP in a horse with an auriculopalpebral nerve block is 20.75 to 31.92 mm Hg, but sedation can cause IOP to decrease¹). A fundic examination of the right eye could not be performed because of corneal, anterior chamber, and lens opacity. Ophthalmic examination findings for the left eye were considered normal with the exception of an incipient anterior cortical cataract. The IOP in the left eye was 16 mm Hg. No abnormalities were noted on physical examination. Ocular ultrasonography of the right eye revealed diffuse iris thickening with an echogenic mass effect and small, punctate areas of mineralization. There was a large, broad-based mass, likely originating from the iris, that extended to the medial and ventral aspects of the iris surface. Within the mass, there were multifocal hyperechoic foci of mineralization. A large area of the mass was situated along the medial aspect of the iridocorneal angle and extended laterally to involve approximately 70% of the iris. Doppler ultrasonography revealed vascularity within the mass that extended in a circular pattern around the medial aspect. There were no retrobulbar abnormalities.

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Photograph of the right eye of a 13-year-old bay Arabian gelding. The eye had appeared painful with blepharospasm and epiphora for 2 months according to the owner. Notice the moderate to severe diffuse corneal edema with corneal vascularization, which made ophthalmic examination of the anterior segment of the right eye difficult. A complicated superficial corneal ulceration is present at the ventral aspect of the cornea (arrow), and the iris is irregular with a focal area of depigmentation and yellow discoloration (asterisk).

Citation: Journal of the American Veterinary Medical Association 258, 6; 10.2460/javma.258.6.583

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Cytologic Findings

Aqueous humor paracentesis was performed on the right eye. Direct smears and cytocentrifuged samples of aqueous humor underwent cytologic examination, which revealed many individualized and occasionally aggregated mononuclear cells. Most of these cells were large mononuclear cells each with a round to irregularly shaped nucleus and vacuolated cytoplasm, consistent with macrophages. They were frequently observed to contain phagocytized RBCs, cellular debris, or green-black pigment that ranged from fine granular to coarse globular material. There were lower numbers of small lymphocytes. Rare mononuclear cells with a moderate amount of cytoplasm completely obscured by dark green granulation were interpreted as likely pigmented cells (melanocytes) of the iris stroma or ciliary body (Figure 2), although hemosiderophages were also considered. Following Prussian blue staining, some pigmented cells were positive for iron (hemosiderophages), whereas others were negative for iron (consistent with either melanocytes or melanophages). Some pigmented cells were negative for the macrophage marker CD204, and this result was supportive of the presence of melanocytes.

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Photomicrographs of cytocentrifuge preparations of aqueous humor acquired via paracentesis from the right eye of the horse. A—The aqueous humor has a moderate number of large mononuclear cells that occasionally contain dark blue-green pigment. Wright-Giemsa stain; bar = 50 mm. B—Some of the pigment stains positively for iron (blue arrow), whereas the pigment in other cells is negative for iron (yellow arrow). Prussian blue stain; bar = 50 mm. C—Some of the large mononuclear cells are immunoreactive for the macrophage marker CD204 (red arrow), whereas other cells, including some highly pigmented cells, are negative for CD204 (green arrow). Immunocytochemical reaction for CD204 with fast red chromogen; bar = 50 mm.

Citation: Journal of the American Veterinary Medical Association 258, 6; 10.2460/javma.258.6.583

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Histopathologic Findings

Because of the horse's poor response to medical management and its grave prognosis for vision and comfort, the right eye was enucleated. The referring veterinarian performed the standing enucleation, and the globe was fixed in formalin and submitted for histologic examination. The horse developed colic following the enucleation surgery but recovered completely with no recurrence of colic.

Grossly, the anterior aspect of the uvea of the enucleated eye was distorted by a variably pigmented tan to dark brown mass, which more severely affected the upper portion of the iris base (Figure 3) Microscopically, the mass was densely cellular and multifocally necrotic; cells were arranged in solid sheets. The bulk of the mass was composed of plump, nonpigmented cells with pale eosinophilic and variably vacuolated cytoplasm (balloon cells). Approximately 50% of the cells in the heavily pigmented regions were spindle shaped to stellate, and the remainder were plump polygonal cells. Nuclei were variably shaped with coarse to vesicular chromatin and generally 1 or 2 nucleoli. Anisocytosis was marked and anisokaryosis was moderate. There were approximately 10 mitotic figures/10 hpf (400×) in the most proliferative regions, and mitotic activity was quite variable. Clusters of cells had exfoliated into the anterior chamber and lined trabecular beams in the ciliary cleft and much of the inner, inferior aspect of the Descemet membrane.

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Photograph of the enucleated and parasagittally sectioned right globe (A) and photomicrographs of sections of the anterior segment (B and C) of that globe. A—The cornea is toward the top of the image, and the upper aspect of the globe is to the right of the image. The entire iris is thickened by a tan to dark brown, mottled mass effect (red arrows), and the largest swelling on the superior leaflet was observed ultrasonographically. There is pigment on the anterior aspect of the lens capsule (yellow arrows) and hemorrhage in the anterior chamber (white asterisk). Bar = 1 cm. B—The iris leaflets (I) are markedly expanded by a densely cellular and largely nonpigmented mass. The upper leaflet (toward the left of the image) is more extensively expanded, corresponding to the pale nodule in the gross image. There is hemorrhage around the pupil margin (blue arrow), along with some cellular debris in the anterior chamber. Chronic keratitis with edema and peripheral neovascularization in the cornea (†) is evident. Breaks in the Descemet membrane (black asterisks) are artifacts of processing. H&E stain; bar = 1 mm. C—At higher magnification, most cells in the field are plump and polygonal with very pale to vacuolated cytoplasm (balloon cells). Nuclear atypia is moderate; anisokaryosis is moderate and nucleoli are prominent. There are multiple mitotic figures (yellow arrows). The cells are more pigmented toward the left of the image with more spindle-shaped and stellate cells. To the right of the image, there is a swath of necrotic cells (black asterisk) that subtends the iris pigment epithelium along the posterior aspect of the iris (not shown). H&E stain; bar = 50 μm.

Citation: Journal of the American Veterinary Medical Association 258, 6; 10.2460/javma.258.6.583

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Morphologic Diagnosis and Case Summary

Morphologic diagnosis and case summary: anterior uveal balloon cell melanoma with secondary chronic glaucoma, mild lymphoplasmacytic uveitis, mild intraocular hemorrhage, chronic nonulcerative keratitis with edema and peripheral neovascularization, and segmental retinal separation in a horse.

Comments

The owner was contacted for an update on the horse 220 days after enucleation of its right eye. The horse was reported to be doing well, with no evidence of systemic disease.

In the case described in the present report, the amount of nuclear atypia and proliferative activity of the mass warranted a diagnosis of malignant melanoma despite a lack of evidence of metastasis. For this horse, given the absence of other dermal melanomas at the time of enucleation and the lack of apparent dermal melanomas or systemic signs suggestive of internal melanomas at 220 days following surgery, the tumor was presumed to be a primary uveal melanoma. Signs of internal melanomas include weight loss, signs of depression, neurologic deficits, colic, and respiratory difficulty.^2,3 The horse of the present report developed colic following the enucleation surgery, but the colic event was believed by the referring veterinarian to be attributable to stress and sedation; moreover, the horse recovered completely from the colic event with no recurrence. On the basis of the case described in the present report, clinical signs that could suggest balloon cell uveal melanoma in a horse include severe anterior uveitis with aqueous flare, a miotic pupil, and either decreased IOP or secondary glaucoma. Although the aforementioned systemic signs were not noted by the owner during the follow-up period, subsequent metastasis to the internal organs may have occurred. Nongray horses are reported to have a higher incidence of malignant melanoma, compared with that among gray horses; gray horses more commonly have multiple, benign melanocytomas.^3,4,5

On review of the veterinary medical literature, no reports of balloon cells in any type of equine melanoma were found by the authors. Two dogs with balloon cell melanoma have been described.^6,7 One of those reported canine cases of balloon cell melanoma also was presented initially with uveitis, but that melanoma infiltrated mostly the iridocorneal angle, uveal tract, and retina.⁶ Balloon cell uveal melanoma in 2 humans has been reported.⁸ Only 1 of those 2 people had uveitis, whereas both complained of decreased vision and had tumors that infiltrated the choroid.⁸ In contrast to the horse of the present report, the human and canine balloon cell uveal melanoma cases had evidence of possible metastasis. One human had metastasis to the liver detected 4 years after the initial diagnosis of a malignant balloon cell choroidal melanoma had been made.⁸ The dog with balloon cell melanoma and uveitis had undergone left forelimb digit amputation because of a chronic lesion 8 months prior to evaluation; the lesion had been nonresponsive to antimicrobials. Unfortunately, the digit was not submitted for histologic examination, and possible melanoma could not be verified.⁶ On presentation, the dog also had an enlarged prescapular lymph node, which was diagnosed histologically as melanoma.⁶ Aqueous humor paracentesis was also performed on that dog; findings for the examined sample of humor were interpreted as mild inflammation with suspected neoplasia of unknown origin.⁶ Following euthanasia of that dog, there was evidence of neoplasia in the diaphragm, lungs, kidneys, left eye, prescapular and submandibular lymph nodes, and skin.⁴ Owing to the convoluted history of a chronic digit lesion and multiple tumor sites, it was unclear whether the ocular melanoma was the primary tumor in that case.⁶

For the horse of the present report and the dog with balloon cell melanoma and uveitis,⁶ the iris of the affected eye was irregular. The horse's eye also had areas of iridial depigmentation and yellow discoloration of the iris. One of the humans with balloon cell uveal melanoma also had a nonpigmented mass, whereas the other person had a partially pigmented mass.⁸ In general, the balloon cell phenotype is not known to have prognostic importance but can be a diagnostic challenge when pigmented regions are not present.

To the authors' knowledge, the balloon cell phenotype of equine melanomas has not been previously reported. Although the balloon cell uveal melanoma did not appear to impact the outcome for this horse, it is important to document equine melanomas with this phenotype. Evaluation of additional cases of equine balloon cell uveal melanoma is warranted to assess the potential for severe uveitis and secondary glaucoma and to better characterize the prognosis for the globe and the patient. This case also highlighted the usefulness of ultrasonography of the globe and cytologic examination of aqueous humor samples to establish an index of suspicion for neoplasia in horses and the potential of the findings of these diagnostic techniques to contribute to timely enucleation of globes with malignant behavior.