Ocular neoplasia and treatment (Proceedings)

Given the plethora of locations and types of neoplastic disorders of the canine and feline eye, this hour long lecture cannot possibly do more than scratch the surface of this subject matter. We can divide the subject material by the following anatomic locations: eyelid, conjunctiva and third eyelid, cornea/sclera, uvea, optic nerve, and orbit, and by species given the differences in disease progression.

Eyelid neoplasia in dogs

Approximately 75%-85% are benign. Most present as brown proliferative or verrucous, usually slow-growing lesions involving the lid margins and meibomian glands. Some may grow to be quite large (see lecture slide show). More than 50% of these masses are sebaceous adenomas, epitheliomas, and adenocarinomas. Squamous papillomas (more papillary in appearance, may be viral in origin and part of papilloma complex) and melanocytomas (Weimeraners and Vizlas appear to be over-represented) are the next most common – approx 25%. Melanomas of the lid margin appear to behave in a benign fashion and are sensitive to excision or cryosurgery in dogs. Ten such other tumor types have been reported such as histiocytomas (young dogs, pink circular masses, that may spontaneously regress), fibromas, lipomas, mast cell, basal cell, and squamous cell tumors, but make up only 10% or less. Small snip or 2-3mm punch biopsies from large infiltrative masses can provide a diagnosis if reconstructive blepharoplasty is anticipated (greater than 1/3 lid length), or simple excision or cryotherapy of small proliferative and benign appearing masses may be curative. Expect recurrence 10-15% of time. Performing histopathology on excisional procedures is recommended as follow up treatment may be necessary. Surgical lid reconstruction will be addressed in our wet-lab. Needle aspirates of lid masses are often non-diagnostic in dogs.

Feline: In general, unlike dogs, most of these tumors are malignant. Some such as SCC may metastasize to regional lymph nodes and other organs (usually very late though – average 5 years for lid SCC in cats). The most commonly reported lid tumors in cats are SCC (Graefe'sArchv245n8p1217-1220 ;VOv10n6p337-343), basal cell carcinoma, mast cell tumors, fibromas/fibrosarcomas, hemangiosarcoma, melanoma, lymphosarcoma, adenomas, and peripheral nerve sheath tumors (VOv8n3p153-158 '05 Hoffman, Blocker, Dubielzig). Apocrine gland hidrocystomas are benign cystic tumors that appear as multiple dark brown proliferative masses around the lids, often seen in brachycephalic cats that can be excised if needed. (JAVMA 15;230(8):1170-3.;VO 7(2):121-5). Needle aspirates, cytology, or biopsies of lid masses in cats prior to surgery is recommended given most are malignant and this will help when deciding on the need for wide-surgical excision, or when pre-surgical treatments (radiation) may be necessary. SCC's are usually locally invasive and ulcerative (vs. proliferative in horses and cattle) lesions in mostly white cats – (13x more common than other colors) – surgical excision with wide margins and adjuvant radiation or cryotherapy is the most successful treatment. Many other treatments reported in literature but less available to us (photodynamic therapy, radioactive gold beads, etc).

Conjunctiva and third eyelid

Canine conjunctival neoplasms

Most are benign but can be locally aggressive.

Squamous papilloma (17%); Nodular granulomatous episcleritis (NGE) – 16%

Vascular neoplasia (hemangioma/hemangiosarcoma) – 15% ; Mast cell tumors – 6%

Nictitans adenocarcinoma – 5% ; Conjunctival melanomas 10-20%? (and many other less common types): Most melanomas are malignant by morphologic criteria and can grow to be quite locally aggressive; most will recur elsewhere on the conjunctiva when removed, but they seldom metastasize. Those on the palpebral conjunctiva are more likely to metastasize– but reports of metastasis are lacking in the literature. Data obtained from Dr. Brian Wilcock.

Feline conjunctival/nictitans neoplasia

Lymphoma is most common. Local edema and tan/white color to conjunctiva is hallmark. This is usually part of multicentric disease and may be a cutaneous epitheliotropic lymphoma manifestation. Fibrosarcoma, SCC and hemangiosarcomas are also reported. Hemangiosarcomas appear very vascular, protuberant tissue, bleed easily (VOv9(4)227-231) and are treated with excision and cryotherapy. Malignant melanoma (rare) – may develop pulmonary metastasis, and tends to be locally aggressive with recurrence. Lipogranulomas are benign tumor-like inflammatory lesions and appear multiple tan/white plaques on the palpebral conjunctiva adjacent to the lid margin—these cats are often blepharospastic. Biopsy reveals granulomas around bases of meibomian glands – treated by local excision of affected conjunctiva. Thought to be UV induced. Cats often have local SCC as well with this disease.

Tumors of the canine/feline cornea/limbus/sclera

Corneal neoplasia is rare in dogs and cats. Choriostomas such as corneal dermoids are seen in a variety of breeds and are treated with local keratectomy, or when they affect the conjunctiva/lid with blepharoplasty. The most common corneal tumor of young dogs is a proliferative papilloma as part of the suspected viral papillomatosis complex. Squamous cell carcinoma of the cornea is reported in brachycephalic breeds that often have a history of KCS, heavy vascular in-growth and treatments with topical CSA or tacrolimus. Other less common tumor types such as hemangiosarcomas have been reported. Some may be amenable to surgical keratectomy or medical therapy, but most are locally aggressive and recurrent. These tumors in cats are extremely rare, biopsy is always warranted.

Limbal (epibulbar) melanocytomas are seen most commonly in German Shepherds and Retrievers. Rarely are these seen in cats. These tumors present as typically circular and darkly pigmented masses along the limbus. Some are more aggressive and extend through the sclera, but tend not to invade orbital tissues, nor do they metastasize. These must be differentiated from pigmented uveal malignant melanoma that may extend through the sclera. If limbal lesions appear superficial, local keratectomy with adjuvant cryotherapy or diode laser photoablative therapy with conjunctival grafting can be performed. For more extensive or full thickness lesions, full thickness sclerectomy and homologous scleral grafting is attempted, but more complications are expected with full thickness procedures (severe uveitis, hyphema, etc). Early diagnosis and treatment affords the best long term prognosis.

Scleral masses in dogs can take on many appearances and several clinical entities are described in the veterinary literature. Most of these conditions are inflammatory and benign and commonly fall under the diagnosis of granulomatous episcleritis or scleritis. Local proliferative lesions consist of populations of histiocytes, lymphocytes and plasma cells. All are treated with immunosuppressive medications. Whereas some are responsive to treatments with topical, subconjunctival or systemic steroids and occasional topical CSA, others may require treatment with oral Immuran or require surgical excision. Treatments with oral tetracyclines and niacinamide therapy have been reported in the literature. Lesions often recur if treatment is discontinued. Cocker Spaniels are over-represented.

Scleral masses in cats are usually an extension of intraocular melanoma or tumors of the conjunctiva (lymphoma) mistaken for scleral masses.

Uveal neoplasia in dogs

Primary intraocular anterior uveal melanocytomas account for over 90% of these tumors. Almost all of these tumors are behaviorally benign, heavily pigmented and locally aggressive. Rates of reported metastasis are extremely low (3-4%) and most veterinary ophthalmologists recommend enucleating affected globes when vision is lost, the eye becomes uncomfortable, glaucomatous, does not respond to topical therapy, or it is simply unsightly to the owner. The largest study of canine intraocular melanomas showed that the tumor size, degree of invasion by the tumor, and the mitotic index were not reliable predictors of survival (VOv2p185-190 '99), however dogs with malignant melanomas had shorter survival times in general compared to more benign lesions. This is in contrast to the dogma that these tumors are of no clinical significance other than how they affect the eye, so maybe we should be more aggressive with these. Most (95%+) of melanocytic in dogs are of anterior uveal origin (iris and ciliary body) and approximately 5% are choroidal. In their early stages these may be treated with Nd:Yag or diode lasers (photoablation), or cryotherapy, but may recur.

Iridociliary epithelial tumors (adenoma, adenocarcinoma) account for 7% of intraocular masses, and all are believed to be benign. All other iridociliary tumor types (medulloepithelioma,spindle cell tumors of blue-eyed dogs, etc are extremely rare – 1% or less of submissions). If tumors are small and confined to 3-4 or less clock hours, attempts at removal via iridocyclectomy or ididectomy can be done, but complications (hemorrhage, retinal detachment) and recurrence are frequent. These masses tend not to be responsive to other treatments (laser ablation) given they are usually not heavily pigmented.

Uveal neoplasia in cats

Approximately 90% of uveal neoplasias in cats are diffuse iris melanomas (10%) are early iris melanomas or). The early stages of feline diffuse iris melanoma are confused with early melanoma, melanosis and iris nevi. In early feline diffuse iris melanoma, tumor is usually confined to the iris. The prognosis appears dependent on mitotic rate, cellular atypia, the extent of infiltration into outflow channels of the eye, and clinically, the development of secondary glaucoma. Metastatic rate in cats much higher than in dogs (35-65%), but are usually late to metastasize. Pre-surgical chest radiographs and abdominal ultrasound are recommended when obviously advanced tumors are to be removed with enucleation or when secondary glaucoma is already present.

Feline iridociliary epithelial tumors are rare (approximately 3-4% of submissions). These tumors tend to be non-pigmented, solid or cavitated, and about 1/2 have metaplastic bone seen on pathology. These are not known to typically metastasize in cats.

Feline post-traumatic sarcomas: (8-9% of feline submissions)

Spindle cell and round cell variants are seen. Spindle cell variants are of lens epithelial origin and Round cell variants are thought to be a variant of lymphoma. There are also a subset that include osteo and chondrosarcomas, but these are very rare and have an unknown cell of origin. The reasons that ocular pathologists feel these are related to trauma include the facts that there is lens capsule rupture, that there is a history of trauma or "abnormal" eye. The time between trauma and tumor is between 2 months and 15 years. These are aggressive tumors in cats and have a propensity for spread along the optic nerve and meninges to affect the central nervous system (and hence can be fatal). Cases that have extended beyond the sclera have a poor prognosis with local recurrence and extension towards the brain. Cases removed within the sclera have a good prognosis, so if intraocular tumor is present years post-trauma, enucleation is the treatment of choice. According to Richard Dubielzig, 8% of traumatized feline globes that were removed prophylactically have early post-traumatic sarcomas!

Canine orbital neoplasms

Average survival time with or without treatment – 5 months.

Most orbital neoplasms in dogs are primary (90%) and malignant (75%). Average age 9 yrs. Usually non-painful progressive exophthalmos. Most common include adenocarcinoma, osteosarcoma, rhabdomyosarcoma, fibrous histiocytoma, neurofibrosarcoma, many others including orbital meningiomas.

Orbital meningiomas in dogs can arise from secondary extension of an intracranial neoplasm along the optic nerve, or from neoplastic transformation of arachnoid cap cells within the optic nerve sheath. Generally they are slow growing and benign, but intraocular invasion and extracranial metastasis has been reported. Exophthalmos, papilledema and blindness with abnormal optic disc appearance is hallmark. Most other orbital tumors do not cause blindness. Exenteration of the orbit is recommended and a fair rate of recurrence is likely. Interestingly often contralateral blindness will occur recurrence over time.

Canine orbital lobular adenomas (lacrimal or salivary): Patients often present with swollen lids, protrusion of the nictitans, and conjunctival masses are seen (this is not common with most orbital masses).

Secondary tumors: nasal carcinoma common. Multilobular tumor of bone.

Katia Attali-Soussay, Jean-Pierre Jegou, Bernard Clerc. Retrobulbar tumors in dogs and cats: 25 cases. VO 4 (1), 19–27.

Feline orbital neoplasia

14-40% primary, 71% secondary(invading orbit from adjacent tissues). 14% are a manifestation of multicentric disease. Most (86%) are malignant. Clinical signs: exophthalmos, strabismus.

SCC and tumor of bone most common (osteoma, OSA). Soft tissue tumors include fibrosarcoma, lymphoma, meningiomas, others. Most are malignant with poor prognosis. Gilger et al. JAVMA 1992 Oct 201(7):1083-6

Canine ocular metastatic tumors

In one pathology series, (31/240) were of epithelial origin (carcinomas); However, most were sarcomas: 10% are hemangiosarcoma.10-15% are histiocytic sarcomas (Retrievers and Rottweilers over-represented) 50% or more are lymphosarcoma; Less common are osteosarcomas, melanomas, and spindle cell tumors.

Feline ocular metastatic tumors

Systemic lymphoma along with histologic evidence of uveitis are most common. Intraocular carcinomas>sarcomas of various origins. Mammary adenocarcinoma, bronchogenic carcinoma, hemangiosarcoma and SCC are most common.

**Various treatment case examples were provided in the lecture portion, please contact me for more information if needed.