JPC SYSTEMIC PATHOLOGY
Signalmnent (AFIP 2149189): German shepherd dog
HISTORY: This German shepherd military working dog was euthanized following diagnosis of multicentric lymphoma. At necropsy, the cornea of the left eye was opaque.
HISTOPATHOLOGIC DESCRIPTION: Slide 2A: Eye: Arising from the iris, expanding and effacing the remaining iris and ciliary body, infiltrating and partially blocking the filtration angle, and infiltrating the cornea and sclera is a large, multinodular, poorly demarcated neoplasm that fills and expands the anterior compartment. Neoplastic cells are arranged in short streams and bundles on a fine fibrovascular stroma and are characterized by: variably distinct cell borders, a moderate amount of eosinophilic cytoplasm that contains abundant dark brown granular pigment (melanin) that often obscures the nucleus, round to oval nuclei with finely stippled chromatin and often a single, prominent nucleolus. The mitotic rate is 0-1 per 10 HPF 40x fields. Multifocally there are variably sized areas of coagulative necrosis admixed with free melanin granules. Scattered throughout and surrounding the neoplasm are numerous melanomacrophages, occasional lymphocytes and plasma cells, and rare single cell necrosis. Multifocally dissecting the neoplasm and adhered to the posterior capsule of the lens is a broad band of collagen admixed with fibrin, melanocytes and melanophages (cyclitic membrane). Diffusely the retina is absent and the remaining underlying retinal pigment epithelium is hypertrophied (“tombstoning”).
MORPHOLOGIC DIAGNOSIS: Eye, uvea: Melanocytoma, German shepherd dog, canine.
Signalment (AFIP 2348405): Tissue from a cat
HISTORY: There is a white to pale yellow-colored nodule involving the ciliary body and iris.
HISTOPATHOLOGIC DESCRIPTION: Slide 2B: Eye: Diffusely expanding the iris and ciliary body up to 2.5 mm, infiltrating the adjacent sclera, and blocking the filtration angle is an unencapsulated, poorly demarcated, polygonal to spindle cell neoplasm. Neoplastic cells are arranged in nests and packets and, rarely, form short streams that encompass multiple small caliber dilated vessels and are separated by a scant fibrovascular matrix. Neoplastic cells have variably distinct cell borders and a moderate amount of finely granular eosinophilic cytoplasm. Occasionally the cytoplasm contains a brown granular pigment (melanin). Nuclei are round to oval with finely stippled chromatin and a single prominent nucleolus. Mitoses average 1-2/HPF. Scattered throughout the neoplasm are melanomacrophages and multifocal single cell necrosis. Multifocally within the posterior chamber there is a moderate amount of fibrin.
Slide 2C: Warthin-Starry 3.2: Many of the neoplastic cells contain variable amounts of intracytoplasmic, silver-positive (agyrophilic), granular material (melanin).
MORPHOLOGIC DIAGNOSIS: Eye, iris: Melanoma, diffuse, breed not specified, feline.
ETIOLOGIC DIAGNOSIS: Ocular melanoma
· Anterior uveal melanocytoma is by far the most common intraocular tumor in dogs
· Primary melanomas of the eye and adnexa are common in the dog and cat, less common in the horse
· Biological behavior of ocular melanomas depends heavily upon species and location
· Melanomas arise in the skin of the lid margin, conjunctiva, anterior uvea, limbus and choroid
· In dogs, intraocular tumors typically arise from melanocytes in the root of or adjacent to the ciliary body (anterior uveal melanocytoma)
· Feline diffuse melanomas start as patchy iris hyperpigmentation that very slowly progresses to diffuse iris hyperpigmentation and thickening over several years; the eventual outcome is virtually always glaucoma
TYPICAL CLINICAL FINDINGS:
· Anterior uvea (most common intraocular tumor in dogs): These are usually benign; a mitotic index greater or equal to 3per 10 HPF indicates malignancy
· Lid margin (second most common): Typically benign
· Conjunctiva (infrequent): Histologically and behaviorally malignant
· Limbus, epibulbar: Histologically and behaviorally benign; composed of large plump melanocytes
· Choroid (rare): Benign; can cause retinal detachment resulting in infiltration of overlying retina and adjacent optic nerve
· Feline diffuse iris melanomas (FDIM, most common site in cats): Usually present with a diffuse iris thickening and hyperpigmentation; Metastasis occurs but is hard to predict and has been linked to large tumor size and intrascleral spread; metastatic foci grow very slowly and rarely cause clinical signs; FDIM often leads to glaucoma
· Conjunctiva (rare): Histologically and behaviorally malignant
· Limbus: Histologically and behaviorally benign
· Most horses with intraocular melanocytic neoplasms have cutaneous melanoma
· The iris is most often affected
TYPICAL GROSS FINDINGS:
· Pigmented expansile nodules that can spread transclerally and circumferentially within the globe
· Glaucoma from occlusion of the ciliary cleft occurs in about half of affected dogs
· Uveitis and hyphema are frequently associated conditions
· Feline iridial melanomas present with diffuse iridal thickening, hyperpigmentation (although they can sometimes be poorly pigmented), and glaucoma
TYPICAL LIGHT MICROSCOPIC FINDINGS:
· Uveitis from tumor necrosis and hyphema from tumor induced neovascularization are often seen
· Anterior uvea: These neoplasms usually arise from the melanocytes of the iris root or adjacent ciliary body and are composed of lightly pigmented spindle cells and usually fewer heavily pigmented plump melanocytes identical to those of limbal melanomas
· Lid margin: Resemble benign cutaneous melanomas
· Conjunctiva: Well pigmented, bland melanocytes with little anisokaryosis or mitotic activity with invasive clusters of angular epithelioid cells with marked anisocytosis and numerous mitotic figures
· Limbus, epibulbar: Large plump melanocytes with a central nucleus and abundant cytoplasmic pigment; few or no mitoses
· Choroid: Well-pigmented, cytologically bland, often with retinal detachment
· Diffuse iridal melanomas infiltrate the stroma of the iris, the ciliary cleft, overlying sclera, peripheral cornea, and ciliary body
· Pleomorphic cells varying from spindle to multinucleated epithelioid cells; light pigmentation with foamy eosinophilic cytoplasm and distinct cell borders
ADDITIONAL DIAGNOSTIC TESTS:
· Bleaching with permanganate or oxalic acid often aids in cytomorphologic interpretation of heavily pigmented neoplasms
· Warthin-Starry 3.2, Fontana-Masson method, immunohistochemical staining
· Electron microscopy may be used to verify melanocytic origin
· Pigmented uveal nodules (uveal cysts). These fluid-filled cysts may be congenital or arise secondary to trauma or inflammation and are benign incidental findings, non-progressive and non-neoplastic
· Canine diffuse uveal melanosis: Distinct clinical entity with diffuse growth pattern within uvea; may be indistinguishable form uveal melanoma; common in Cairn terriers
· Common locations for melanomas in different species:
· Conjunctiva: Canine, feline, porcine
· Eyelid: Rat
· Anterior uvea, iris: Canine, equine (young, grey horses), bovine, feline, rodent (F344 rat)
· Choroid: Canine
1. Beckwith-Cohen B, Teixeira LBC, Dubielzig RR. Presumed primary intraocular chondrosarcoma in cats. J. Vet. Diag. Invest. 2014; 26(5): 664-668.
2. Dubielzig RR, Ketring KL, McLellan GJ, Albert DM. Veterinary Ocular Pathology: A Comparative Review. New York: Saunders Elsevier; 2010;162-165,184-187, 282-290.
3. Labelle P. The Eye. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St Louis, MO: Elsevier; 2017; 1302-1304.
4. Wilcock BP, Njaa BL. Special senses. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St Louis, MO: Elsevier Saunders; 2016; 482-485.