Signalment:  

Seven-year-old male castrated Siamese cross, feline (Felis cats)The cat presented with a mass on the left iris of unknown duration. An aspiration of the iris was diagnosed as a plasmacytoma. Chemotherapy was attempted with no response. The left eye was enucleated and submitted for histopathological diagnosis.

Gross Description:  

There was a 1cm mass expanding the ventral iris.

Histopathologic Description:

Eye (left), anterior uvea: Diffusely expanding the iris, ciliary body, irido-corneal angle, and infiltrating into the adjacent sclera and uvea, and protruding into the anterior chamber is an unencapsulated, highly cellular, poorly demarcated neoplasm arranged in closely packed sheets, streams and bundles, and vague packets separated by a thin fibrovascular stroma. Neoplastic cells exhibit two morphologic forms. The first is a pleomorphic round cell with distinct cell borders, abundant granular eosinophilic to clear cytoplasm, and 1-2 large round to irregular often peripheralized nuclei with coarsely stippled chromatin and 1-3, large, occasionally irregular, magenta nucleoli. Anisocytosis and anisokaryosis is marked. The second form of neoplastic cell consists of spindle cells with indistinct cell borders, a moderate amount of eosinophilic cytoplasm, a round to oval nucleus with fine to coarsely stippled chromatin and 1-2 nucleoli. Anisocytosis and anisokaryosis is moderate. The mitotic rate in both morphologic populations is highly variable and reached up to 8 mitotic figures per high power field. Rarely, melanin pigment is identified within the cytoplasm of neoplastic cells.

Morphologic Diagnosis:  

Eye, iris, left: Melanoma, diffuse, Siamese cross (Felis cats), feline.

Lab Results:  

Neoplastic cells are immunohistochemically positive for S-100 and melan-A.

Condition:  

Melanoma

Contributor Comment:  

The cat in this case was interesting in that it presented with a visible, white nodule protruding into the anterior chamber. An aspiration of that mass consisted of multiple individualized round cells with abundant clear to pale blue cytoplasm, and 1-2 small round eccentrically placed nuclei. The mass was initially diagnosed as a potential plasmacytoma with a recommendation for removal and confirmation due to the rarity of that particular type of tumor. There is only a single case report by Michau et.al. in 2003 diagnosing an intraocular extramedullary plasmacytoma in a cat.(5)

The differential diagnosis for the gross presentation included nodular iris melanoma and a uveal cyst. On histopathologic examination, the neoplastic melanocytes diffusely infiltrated iridial stroma, ciliary body, and iridocorneal drainage angle and protruded into the anterior chamber resulting in the grossly visible nodule. Melanocytic tumors are the most common primary intraocular neoplasms in cats,(2,7) with intraocular sarcomas and ciliary epithelial neoplasms also occurring with lesser frequency.(3)

Diffuse iris melanoma generally begins as an asymmetrical abnormal pigmentation of the iris that may be clinically noted several years prior to the development of neoplasia.(2) This area of pigmentation may remain static or progress to nodular iridial irregularities and diffusely infiltrate the sclera, ciliary body, and posterior segment.(2) Neoplastic cells originate from melanocytes that line the anterior border of the iris.(9) Rarely, atypical melanomas, not associated with diffuse iris melanoma, may arise multifocally within the limbus or choroid. Little is known about their origin, behavior, and prognosis.(2,4)

Three morphologically distinct neoplastic cells are often found in feline diffuse iris melanoma. These different morphologic cell types may occur in any combination within diffuse iris melanoma, and no prognostic significance has yet been attached to these various combinations.(2,9)

1) Pleomorphic round cells (most common type), consist of cells with abundant eosinophilic cytoplasm and a primarily centralized round nucleus. These cells may occasionally exhibit cytomegaly, cytoplasmic invaginations forming pseudo-inclusions, and variable amounts of pigmentation.
2) Spindle cells (2nd most common).
3) Balloon cells, consist of cells with abundant eosinophilic to clear cytoplasm with a high cytoplasm to nuclear ratio and a small often centralized round nucleus. No prognostic significance has been associated with the morphologic type of neoplastic cells.

Poorly differentiated intraocular melanomas may exhibit a wide variety of morphoglogic and pigmentation characteristics. This often results in a struggle to develop a definitive morphologic diagnosis on H&E alone. Common immunohistochemical stains include HMSA-5, S-100, and tyrosinase.(1)

Feline diffuse iris melanomas are considered more likely to metastasize than canine uveal melanomas, but due to the slow progression of the tumor, the overall risk that an animal will die from the melanoma is less than 20%.(9) In cats, metastasis associated with diffuse iris melanomas has been documented affecting lungs, lymph nodes, skeletal system and abdominal viscera.(6) Predictors of metastasis include scleral invasion, invasion into posterior iris epithelium, and overall tumor size.(9)

Retroviral antigen has been identified in both intraocular sarcoma and diffuse iris melanoma. (1,3,8) In a retrospective study by Stiles et. al. in 1999, 3 of 36 intraocular melanomas tested positive for FeLV-FeSV DNA by nested PCR.7 Another retrospective study in 2002 by Cullen et al failed to find viral DNA sequences in the intraocular melanomas examined in 10 cats.(3)

JPC Diagnosis:  

Eye, ciliary body, iris, choroid: Diffuse melanoma.

Conference Comment:  

Conference participants discussed the presence of ganglion cell layer and inner nuclear layer atrophy likely due to occlusion of the drainage angle by the neoplasm. Occlusion prohibits adequate drainage resulting in an increase in intraocular pressure (IOP) and subsequent development of closed angle secondary glaucoma (6, 10). Histologic findings characteristic of glaucoma are cupping of the optic disk (pathognomonic when present), dilated axonal sheaths, and axonal degeneration and loss. Progressive retinal changes include atrophy of the afferent nerve fiber layer and ganglion cell layer resulting in accentuation of Muller cells, thinning of the inner plexiform and nuclear layers and eventual blending together of the inner and outer nuclear layers, with the retina eventually being reduced to a thin glial scar with few outer nuclear layer remnants and melanophages from the retinal pigment epithelium. Diffuse iridal melanomas are the most common cause of secondary glaucoma in cats. Both increased IOP and degenerative structural changes must be present to warrant a diagnosis of glaucoma (6, 10); however, since IOP was not reported for this cat, and the eye was still visual according to the contributor, the cause of the retinal atrophy can only be speculated.

The contributor mentions uveal cysts, or pigmented uveal nodules, as a gross differential diagnsosis. Uveal cysts are fluid-filled cysts which may be congenital or arise secondary to trauma or inflammation. They are non-neoplastic, non-progressive and considered an incidental finding.

References:

1. Cullen CL, Haines DM, Jackson ML, Grahn BH: Lack of detection of feline leukemia and feline sarcoma viruses in diffuse iris melanomas of cats by immunohistochemistry and polymerase chain reaction. J Vet Diagn Invest 14:340-343, 2002
2. Dubielzig RR: Tumors of the eye. In: Tumors in Domestic Animals, 4th ed., Meuten DJ, ed., pp. 744-749. Iowa State Press, Ames, IA, 2002
3. Grahn BH, Peiffer RL, Cullen CL, Haines DM: Classification of feline intraocular neoplasms based on morphology, histochemical staining, and immunohistochemical labeling. Vet Ophthalmol 9:395-403, 2006
4. Harris BP, Dubielzig RR: Atypical primary ocular melanoma in cats. Vet Ophthal 2:121-124, 1999
5. Michau TM, Proulx DR, Rushton SD, Olivry T, Dunston SM, Gilger BC, Davidson MG: Intraocular extramedullary plasmacytoma in a cat. Vet Opthalmol 6:177-181, 2003
6. Njaa BL, Wilcock BP. The eye and ear. In: Zachary JF, McGavin MD, eds. Pathologic Basis of Veterinary Disease. 5th ed. St. Louis, MO: Elsevier; 2012:1215-20, 1228-9.
7. Planellas M, Pastor J, Torres MD, Pe+�-�a T, Leiva M: Unusual presentation of a metastatic uveal melanoma in a cat. Vet Ophthalmol 13:391-394, 2010
8. Stiles J, Bienzle D, Render JA, Buyukmihci NC, Johnson EC: Use of nested polymerase chain reaction (PCR) for detection of retroviruses from formalin-fixed, paraffin-embedded uveal melanomas in cats. Vet Ophthalmol 2:113- 116, 1999
9. Wilcock B, Dubielzig RR, Render JA: Histological Classification of Ocular and Otic Tumors of Domestic Animals. 2nd Series, Vol. IX, pp.18-19, 24-25. Armed Forces Institute of Pathology, Washington, DC, 2002
10. Wilcock, BP. Eye and ear. In: Maxie MG, ed. Jubb, Kennedy, and Palmers Pathology of Domestic Animals. 5th ed., vol. 1, Philadelphia, PA: Elsevier Saunders; 2007:514-5, 538-42.

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