"Ocular Tumors" TUMOR TIDBITS Volume 2; Number 9; June 1, 2001 Editor: Kevin A. Hahn, DVM, PhD, Dipl - ACVIM (Oncology) & Overall Nice Guy! OCULAR TUMORS INTRODUCTION: Neoplasia affecting either the adnexa (eyelids, conjunctiva, nictitans, or sclera) or uveal tract (iris, ciliary body, choroid), and orbit are relatively common in dogs and cats. The clinical significance and appropriate treatment of these tumors varies considerable depending on the anatomic location, species (dog vs. cat), age of the patient, and whether the neoplasia is primary or metastatic. The purpose of this report is to provide an overview of the common types of ocular and periocular neoplasia in dogs and cats, their clinical significance, expected pattern of growth, and therapeutic options. GENERAL CONSIDERATIONS: Important differences in biologic behavior of these neoplasia exists between the two species, with most primary canine ocular/periocular tumors having a benign behavior, while most primary feline tumors are malignant. As would be expected, most of the tumors occur in older animals, with notable exceptions including eyelid histiocytomas and infectious papillomas in dogs, oncogene-related neoplasia in cats, and certain forms of iris melanoma in dogs. Adnexal neoplasia, when benign, becomes clinically important when it is reaches a size or is in a location that physically irritates the conjunctiva and cornea and causes discomfort. Intraocular benign neoplasia becomes clinically significant when distortion of the uveal tissue or displacement of the lens occurs, and will generally culminate in secondary glaucoma from an obstruction to aqueous humor outflow. Malignant adnexal or intraocular neoplasia has its most important effects by being locally invasive to surrounding tissues, or in causing secondary glaucoma. Orbital neoplasia is general malignant, locally invasive and results in progressive exophthalmos, globe deviation, and protrusion of the nictitans. It should be noted that all ocular and periocular tumors, regardless of their expected microscopic morphology and biologic behavior, should routinely be biopsied to confirm the diagnosis. EYELID NEOPLASIA: In the dog, by far the most common tumor of the eyelid is the meibomian (sebaceous) adenoma. This slow-growing tumor arises from the meibomian gland near the eyelid margin, may be pigmented or non-pigmented, often has a cobblestone surface, and may be associated with a secondary chalazion from obstruction of the gland and a secondary granulomatous inflammation. Other less common eyelid neoplasia includes benign melanoma, papilloma (viral and non-viral), and histiocytoma. Rarely, malignant eyelid neoplasia is seen including mast cell tumor, sebaceous adenocarcinoma, basal cell carcinoma, squamous cell carcinoma, and fibrosarcoma. Benign tumors do not necessary require therapy until irritation of the globe occurs, in which case surgical excision and/or cryotherapy of the lesion is generally used. The latter offers the advantage of being performed in a sedated patient under local anesthesia. Secondary chalazion should be excised and curetted at the time of tumor treatment. Larger or malignant neoplasia of the eyelid generally requires surgical excision. If more than 1/3 of the eyelid margin is removed, a secondary grafting procedure is necessary to restore the functional integrity of the eyelid margin. A variety of surgical techniques are described for this purpose. In the cat, the most common eyelid tumor is squamous cell carcinoma, with lightly pigmented cats being predisposed. Concurrent pinnal or nasal squamous cell carcinoma is common. Other eyelid neoplasia, which tends to be malignant, include basal cell carcinoma, mast cell tumor, fibrosarcoma, and uncommonly, lymphosarcoma. Adnexal squamous cell carcinoma in the cat tends to be very locally invasive, and can be very challenging to treat as surgical excision alone has a reasonable high recurrence rate. Extensive cryosurgery, intralesional chemotherapy, and photodynamic therapy are options for the referral specialists. The usefulness of local radiation therapy is limited by the collateral side effects on the globe. Prognosis is somewhat guarded. Other types of malignant neoplasia of the eyelid are generally treated by surgical excision, with a grafting procedure if the eyelid margin is involved. CONJUNCTIVAL, NICTITANS, AND SCLERAL NEOPLASIA: Neoplasia in these sites is much less common that involving the eyelid. In the dog, the conjunctiva (including that covering the nictitans) may develop hemangiomas or less commonly hemangiosarcomas, melanoma (usually benign) squamous cell carcinoma, and lymphosarcoma. An aggressive, invasive neoplasia, an adenocarcinoma, has been described arising from the gland of the nictitans. Conjunctival or nictitans neoplasia is generally treated with surgical excision alone, with adjuvant therapy used in selected cases. Neoplasia of the conjunctiva must be must be distinguished from pseudoneoplastic or inflammatory nodules, especially an immune mediated inflammation known as nodular granulomatous episclerokeratitis. In the cat, the only common conjunctival neoplasia is squamous cell carcinoma, with the same consideration as eyelid involvement. The only common tumor of the scleral is a melanocytoma arising from the limbal region, (epibulbar melanoma, limbal melanoma, limbal melanocytoma). In both dogs and cats, these are benign, slow growing neoplasms, that relatively late in the course of the growth can invade the cornea and adjacent iridocorneal angle and cause corneal opacity or secondary glaucoma. A limbal melanocytoma with intraocular extension must be distinguished form a uveal melanoma with extraocular extension. Deep surgical excision, often with a tissue graft, early in the course of growth offer the best prognosis for the eye. Other forms of therapy include cryotherapy or laser ablation with a Nd:YAG or CO2 laser. PRIMARY ANTERIOR UVEAL NEOPLASIA: Melanoma is the most common type of primary neoplasia affecting the intraocular tissues. Unlike humans, the anterior uveal tract (iris and ciliary body) is the most common site of involvement. In dogs, anterior uveal melanomas generally manifest as brown to black nodular lesions that protrude from the iris or ciliary body and demonstrate progressive, generally slow growth. When of sufficient size, they may cause secondary glaucoma, corneal edema, lens luxation and uncommonly, intraocular hemorrhage. Diagnosis is made based on appearance, and if the intraocular tissue cannot be visualized, by ultrasonography. Though these tumors are generally seen in older aged animals, recently, an iris melanoma with a presumed heritable basis has been identified in a large group of related young Labrador retriever dogs. Uveal melanomas in dogs are overwhelmingly benign in the sense that they do not metastasize to distant organs. In the largest retrospective study to date, only 6% had evidence of metastasis. A high mitotic index on microscopic examination was the strongest correlate to the likelihood of metastasis. As a result of their slow growth and benign behavior, these tumors are often treated by benign neglect until they result in secondary complications, at which time enucleation is curative. Other treatment options include surgical resection, laser ablation (diode or Nd:YAG lasers), and photodynamic therapy. Of these, diode laser therapy is most widely available. Prognosis depend on the stage at which these are treated and experience of the laser surgeon. In cats, melanomas (also the most common primary intraocular neoplasia) generally present as a multifocal, coalescing areas of iris pigmentation and the term "diffuse iris melanoma" has been used to describe this condition. Diffuse iris melanomas must be distinguished from other benign melanocytic changes in the iris including benign iris melanosis and iris darkening due to chronic uveitis. Melanomas generally are raised above the iris surface and often have pigment exfoliation into the anterior chamber. Biomicroscopic examination by an experienced ophthalmologists may be necessary to diagnosis early iris melanoma in cats. Unlike dogs, retrospective studies suggest that up to 50-60% of these tumors metastasize. A recent study also documented a substantially shorter life span, presumably from metastatic disease, in cats with iris melanoma vs. age matched cats. However, these tumors often exhibit very slow growth (months to even years to progress over the entire iris) and a long interval between detection (or even enucleation) and the onset of metastatic disease. As a result, there is considerable controversy in how best to treat these tumors. Some ophthalmologists recommend neglect until secondary glaucoma ensues (this is the most common adverse sequella), while others, recommend early enucleation once a diagnosis is reasonably certain. There is some evidence in two studies reported in the literature that early enucleation may lessen the likelihood of metastasis, but this point is still uncertain. The second most common (and only other common primary intraocular neoplasia) is an adenoma or adenocarcinoma arising from the ciliary body epithelium. This tumor can occur in dogs and cats, is often a non-pigmented nodule arising in the ciliary body and protruding through the pupil, and exhibiting slow growth and benign (non-metastatic) behavior. Treatment options and philosophies are similar to anterior uveal melanomas. A rare congenital tumor, termed a medulloepithelium and arising from the ciliary body has also been described in dogs. Previously traumatized feline eyes are also at risk for development of a primary ocular sarcoma (also called post-traumatic sarcoma). Often, a long latent period of 1-10 years between a history of trauma and onset of clinical signs is reported. Most cases appear to be associated with lens capsule rupture, and many veterinary pathologists feel the tumor arises from the lens epithelia. The tumors progressively fill the ocular cavity, invade and extend outside the sclera, and late in the course locally invade the central nervous system and regionally metastasize. Mortality rate appears to exceed 90%. Early enucleation or exenteration is the only available treatment and because of this high mortality rate, many clinicians recommend surgical removal of traumatized feline eyes that are blind, even if non-painful, to prevent tumor development. SECONDARY ANTERIOR UVEAL NEOPLASIA: Although uncommon, virtually any malignant neoplasia can metastasize to the uveal tract, most commonly the anterior uvea. Generally, the neoplasia is evident in other organs, but occasionally, clinical signs in the eye (nodule formation, hemorrhage, secondary glaucoma), may be the presenting complaint. The primary importance in this cases is in distinguishing primary vs. metastatic ocular neoplasia. As the two can appear similar, it is important to perform a thorough physical examination, routine clinicopathologic tests, and chest and abdominal imaging studies in any animal with suspected ocular neoplasia. The most common secondary ocular neoplasia is lymphosarcoma, and some reports suggest that up to 35% of dogs with multicentric lymphoma have ocular manifestations. In dogs, the most common manifestation is in the anterior uvea and mimics signs of anterior uveitis including diffuse iridal thickening, aqueous flare, hypopyon, low intraocular pressure, and occasionally secondary glaucoma. In dogs, ocular involvement has been exclusively seen with multicentric disease, and the diagnosis is generally not difficult. Occasionally, the eye will be the predominate organ involved and a anterior chamber paracentesis may be useful to establish a (cytologic) diagnosis, but this is the rare exception. In cats, uveal lymphoma may present as either a diffuse thickening of the iris, a non-pigmented nodule on the iris or ciliary body, or multifocal to diffuse retinal and choroidal lymphoblastic infiltration, manifesting as retinal hemorrhage, retinal edema or retinal detachment. While feline ocular lymphosarcoma is usually associated with other organ involvement, there is recent evidence that a form of primary ocular lymphosarcoma may exist in cats, and that this type of neoplasia may be associated with a better survival prognosis. ORBITAL NEOPLASIA: Neoplasia involving the orbit or periorbital region is reasonable common in both dogs and cats. Variable but usually slowly progressive exopthalmos, protrusion of the nictitans, deviation of the globe (strabismus), pain on opening the mouth, and occasionally visual and pupillary light reflex deficits (from optic nerve damage) are typical signs in both species. Orbital neoplasia may be primary (tissues within the orbit), extension from adjacent tissues (especially the nasal and paranasal sinuses and oral cavity), or metastatic. The former two categories are the most common. In both species, malignant tumor types predominate in cats, squamous cell carcinoma from extension from the oral cavity is the most common tumor type. Fibroma and fibrosarcoma, osteosarcoma, lymphosarcoma, optic nerve menigioma, (nasal) adenocarcinoma, mastocytoma, and multilobular osteoma have been reported in the dog. Diagnosis is based on clinical and radiographic findings, ultrasonography, CT or other imaging studies, and fine needle aspirate. Biopsy of the mass, if necessary to obtain a diagnosis, requires surgical exploration of the orbit and would generally be a referral procedure. Surgical resection (exenteration) sometimes followed by radiation therapy are the general means of treatment, if pursued. Because these tumors are generally recognized relatively late in the course of the progression, they in general, carry a poor prognosis with limited life span, even with aggressive surgical therapy. COMMENTS At Gulf Coast Veterinary Oncology we recommend a thorough physical examination, survey radiographs of the chest and abdomen, and routine laboratory evaluations (a minimum data base) to rule out systemic illness, systemic neoplasia or metastasis, prior to the consideration of surgical or radiation options for ocular tumors. With the exception of lymphoma, enucleation is an acceptable treatment choice for melanomas. Have More Questions? Don't hesitate to call or email us at Gulf Coast Veterinary Oncology! Kevin Kevin A. Hahn, DVM, PhD, Diplomate ACVIM (Oncology) & Overall Nice Guy Gulf Coast Veterinary Oncology 1111 West Loop South, Suite 150 Houston, TX 77027 www.gcvs.com drhahn@g...