JPC SYSTEMIC PATHOLOGY

SPECIAL SENSES SYSTEM

April 2024

S-N02 (NP)

 

SLIDE A: Signalment (JPC #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: Eye: Arising from the iris, filling 90% of the anterior chamber and 30%% of the posterior chamber, expanding and effacing the remaining iris and ciliary body, infiltrating and blocking the filtration angle, and infiltrating the cornea and sclera is an expansile, multinodular, poorly demarcated, densely cellular neoplasm composed of round to spindloid cells arranged in short streams and bundles on a fibrovascular stroma. Neoplastic cells 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, and a round to oval nucleus with finely stippled chromatin and a single, prominent nucleolus. There are 0-1 mitoses per 2.37mm². Multifocally within the neoplasm, there are variably sized areas of coagulative necrosis admixed with free melanin granules. Scattered throughout and surrounding the neoplasm are numerous melanophages and occasional lymphocytes and plasma cells. Extending from the iris and ciliary body, 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). There is fibrous metaplasia of the subcapsular lens epithelium. Diffusely the retina is detached and severely atrophied, often with only scant nerve fibers remaining; the remaining retinal pigment epithelium is hypertrophied (“tombstoning”).  

 

MORPHOLOGIC DIAGNOSIS: Eye, uvea: Melanocytoma, German shepherd dog, canine.

 

SLIDE B: Signalment (JPC #2348405): Tissue from a cat

 

HISTORY: There is a white to pale yellow nodule involving the ciliary body and iris.

 

HISTOPATHOLOGIC DESCRIPTION: Eye: Diffusely expanding the iris and ciliary body up to 1.9 mm, infiltrating the adjacent sclera, and blocking the filtration angle is an unencapsulated, poorly demarcated, moderately cellular neoplasm composed of polygonal to spindloid cells arranged in packets, sheets, and short streams on a scant fibrovascular matrix. Neoplastic cells have variably distinct cell borders and a moderate amount of finely granular, eosinophilic cytoplasm that occasionally contains brown, granular pigment (melanin). Nuclei are round to oval with finely stippled chromatin and a single prominent nucleolus. Mitoses average 1-2 per individual HPF. Scattered throughout the neoplasm are moderate numbers of melanophages and there is multifocal single cell necrosis among neoplastic cells. Multifocally within the posterior chamber there is a small amount of fibrin. 

 

SLIDE C: Warthin-Starry 3.2 Many of the neoplastic cells contain variable amounts of intracytoplasmic, silver-positive (argyrophilic), granular material (melanin).

 

MORPHOLOGIC DIAGNOSIS: Eye, iris: Melanoma, diffuse, breed not specified, feline.

 

ETIOLOGIC DIAGNOSIS: Ocular melanoma

 

GENERAL DISCUSSION:  

• Anterior uveal melanocytoma is the most common intraocular tumor in dogs
• Primary melanomas of the eye and adnexa are common in the dog and cat, and are less common in the horse    
• Biological behavior of ocular melanomas depends heavily upon species and location  

 

PATHOGENESIS:  

• Melanomas arise in the skin of the lid margin, conjunctiva, anterior uvea, limbus, and choroid
• In dogs, intraocular melanocytic tumors typically arise from melanocytes in the root of or adjacent to the ciliary body (anterior uveal melanocytoma)
  • Senescence markers γH2AX- or p21 are increased in canine eyes with intraocular tumors, particularly those with conjunctival melanoma (Merz, J Comp Pathol. 2019)
• 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 secondary glaucoma  

 

TYPICAL CLINICAL FINDINGS:  

Dogs:

• Anterior uvea (most common intraocular tumor in dogs): These are usually benign; a mitotic index greater than or equal to 3 per 2.37mm² 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

 

Cats:

• 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

 

Horses:

• 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: 

Dogs:

• 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

 

Cats: 

• 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

 

DIFFERENTIAL DIAGNOSIS:

• 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 from uveal melanoma; common in Cairn terriers
• Oculodermal melanocytosis (nevus of Ota): Dermal melanocytic hamartoma which corresponds to the trigeminal nerve ophthalmic and maxillary branches (Giannikaki, Vet Pathol. 2019)

 

COMPARATIVE PATHOLOGY:  

• Common locations for ocular melanomas in different species: 

• Conjunctiva: Canine, feline, porcine
• Eyelid: Rat
• Anterior uvea, iris: Canine, equine (young, grey horses), bovine, feline, rodent (F344 rat), Aradi goat (El-Shafaey, J Comp Path 2020)
• Choroid: Canine
• Concurrent with lacrimal gland: Canine

 

REFERENCES:  

1. 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. 
2. El-Shafaey E, Hamed MF. Uveal melanoma in an Aradi goat (Capra aegagrus hircus).  J Comp Pathol. 2020; 177: 5-9.
3. Giannikaki S, Sturgess K, Scurrell E, Cebrian P, Escanilla N, Lowe R. Oculodermal melanocytosis: nevus of Ota in a dog. Vet Pathol. 2019;56(3):460-464.
4. Labelle P. The Eye. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1406; 1413; 1416-1417.
5. Merz SE, Kershaw O, Petrick A, et al. Tumour, but not age-associated, increase of senescence γH2AX and p21 in the canine eye markers. J Comp Pathol. 2019;173:41-48.
6. Mitsui I, Nishimura S. Concurrent lacrimal gland melanocytoma and ocular melanocytosis in a dog. J Vet Diagn Invest. 2022;34(1):121-125
7. 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.

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