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Ocular oncology
Ocular Oncology A. Michelle Willis, DVM and David A. Wilkie, DVM, MS
Neoplasia can affect all ocular tissues. The clinical appearance of ocular neoplasia can vary considerably depending on the specific tissue involved. Intraocular neoplasia may mimic or incite ocular inflammatory disease in addition to causing hyphema or secondary glaucoma. Intraocular neoplasms can be primary tumors or may be secondary to metastatic disease or systemic neoplasia. Primary neoplasms, metastatic tumors, tumors extending from adjacent structures, and systemic neoplasms can also affect the adnexal tissues. Many ophthalmic tumors are histologically benign but are locally invasive and, within the confined space of the eye or orbit, can produce significant tissue distortion. Certain ocular neoplasms, such as many canine eyelid tumors, are amenable to simple excision and can be adequately managed in general practice. The evaluation and treatment of other ophthalmic neoplasms, however, may require the additional equipment available only in larger specialty practices, such as computed tomography and radiation therapy. Early diagnosis of ocular neoplasia is an important aspect of successful management. Copyright © 2001 by W.B. Saunders Company
lthough neoplasia uncommonly affects the eyes of companion animals, it should be included on the differential lists for diseases affecting all ocular tissues. Prompt diagnosis of ocular neoplasia is paramount for successful management. This article reviews primary tumors of the eye and ocular adnexa in both cats and dogs as well as secondary tumors that have been reported to metastasize to the dog and cat eye.
A
Primary
Ocular Neoplasia Eyelids
Neoplasms in the eyelids are relatively common in dogs. Eyelid neoplasms are similar to those that occur in the skin generally and arise from epithelial, mesenchymal, and melanogenic cells, i Sebaceous gland tumors, squamous papillomas, and melanomas occur with high frequency in the eyelids of dogs 2,3 and tend to be benign, although progressive growth can be associated with ocular surface irritation. Sebaceous gland tumors generally arise in the eyelids from the meibomian glands and include sebaceous adenoma, sebaceous epithelioma, and sebaceous adenocarcinoma. 1 These tumors present as raised, variably sized, and sometimes pigmented masses (Fig 1). Other less common neoplasms affecting the canine eyelid include basal From the Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, OH. Address reprint requests to A. Michelle Willis, DVM, Rowley Memorial Animal Hospital, 171 Union Street, Springfield, MA 01105. E-mail: [email protected] Copyright © 2001 by W.B. Saunders Company 1096-2867/01/1601-0010535.00/0 doi:10.1053/svms.2001.22810
cell epitheliomas 2-* and basal cell carcinomas (Fig 2), fibromas, fibrosarcoma, neurofibroma, and neurofibrosarcoma. Cutaneous histiocytomas occasionally affect the canine eyelid. Their appearance is characterized by a smooth, hairless, pink exterior with a typically sessile base (Fig 3). This tumor is most often seen in young dogs and is amenable to surgical resection, as they can sometimes be locally invasive but often resolve spontaneously. Primary eyelid neoplasms are rare in cats. Squamous cell carcinoma (SCC) was the most common eyelid neoplasm reported in one series. 5 In this series eyehd neoplasia in general and specifically SCC was most frequent in cats 10 years of age or older. Eyelid SCC usually presents as a proliferative pink to white mass or as a progressive, ulcerated lesion (Fig 4). The medial canthal eyelid is frequently initially affected, and white cats are predisposed. Eyelid SCC has also been reported to metastasize to the orbit. 6 Basal cell carcinoma, 7 mast cell tumor, 8 and fibrosarcoma have also been reported in cats with relatively high frequency.
Diagnosis and Therapy Fine-needle aspiration of an atypical eyelid mass may be helpful from a prognostic standpoint, but in general, surgical removal with full-thickness excision and two-layer closure is recommended if the mass is irritating, undergoes an overt growth rate change, or is prone to bleeding. Up to one third of the length of the lid margin may be removed in a dog with a normal palpebral fissure length. Larger lesions may require wider excision and more extensive surgical reconstruction of the defect. 9-1] Cyrotherapy, hyperthermia, radiation, laser photocoagulation, or local and adjunctive systemic chemotherapy may be effective in the management of specific tumors, particularly those that do not lend themselves to complete surgical excision because of location and extent. Cornea, Sclera, Conjunctiva, and Nictitating M e m b r a n e
Dermoids Dermoids are choristomas that usually develop on the conjunctiva and cross the limbus to involve the cornea; they have been reported in both dogs and cats. 12,13 These congenital tumors can contain keratinized epithelium, fibrous tissue, hair, fat, blood, vessel, nerves, glands, smooth muscle, and cartilage. Hair is usually evident in corneal dermoids, and the corneal irritation induced by long, stiff hairs usually warrants intervention. Treatment is by surgical excision with superficial keratectomy/conj unctivectomy. Squamous Cell Carcinoma Several cases of corneal SCC reported in dogs occurred in eyes with advanced pigmentary keratitis, a condition that commonly
Clinical Techniques in Small Animal Practice, Vol 16, No 1 (February), 2001: pp 77-85
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Fig 3. Histiocytoma of the lower eyelid in a young labrador retriever. The smooth, hairless appearance is typical for cutaneous histiocytoma; however, the diagnosis was confirmed with cytology acquired by fine-needle aspiration. The mass in this dog spontaneously regressed approximately 2 weeks after presentation.
(Fig 5). The tendency to metastasize appears to be rare, based on an absence of reports in the literature. Superficial keratectomy of a corneal lesion may be curative; however, adjunctive therapy with cryosurgery or /3-radiation (commonly strontium90) may reduce local recurrence rate. Addressing the un&flying source of chronic irritation, where applicable, is an important aspect of therapy. Fig 1. Sebaceous adenoma involving the lower eyelid of a middle-aged dog. The orientation of the mass resulted in corneal contact as it grew, inducing intermittent epiphora and blepharospasm.
Papilloma
accompanies chronic corneal irritation. ~4-16 Canine corneal SCC has been associated with chronic keratoconjunctivitis sicca, ~r or keratitis secondary to enophthalmos. ~5 Chronic irritation or trauma to tissues may induce tumor development, 15 so ocular tumors and pigmentary keratitis may share risk factors. > Corneal SCC is characterized by a pink, typically irregular mass protruding from the epithelial surface of the cornea
Papillomas have been described in the canine conjunctiva, the eyelid, and the cornea. 18,19 Corneal papillomas are typically slow-growing and benign and have been seen in association with pigmentary keratitis 1~ but is more typically related to papillomavirus infection in dogs. 18-2° Cutaneous papillomas are rare feline tumors that appear clinically as well-circumscribed, pedunculated, alopecic masses that may involve the eyelid. 2~ Ocular papillomas may spontaneously regress, ~8 however, if the masses are locally irritating, removal is warranted. Excision
Fig 2. Basal cell carcinoma of the superior eyelid of an aged basset hound. The local but extensive invasion of the neoplasm necessitated enucleation. (Courtesy of Jean Stiles, West Lafayette, IN.)
Fig 4. Squamous cell carcinoma (SCC) involving the lower and upper eyelids in an older, white cat. Surface ulceration is typical for SCC at this site.
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WILLIS AND WILKIE
of the conjunctiva in both cats and dogs. Multiple recurrences, necessitating enucleation, have been reported in both species. 23-26 Adjunctive cryotherapy may reduce the risk of local recurrence due to incomplete excision, as neoplastic cells were identified at the surgical margins of several cases thought to be completely excised by the attending surgeon. 23 Preoperauve evaluation for metastatic disease (regional lymph nodes, thoracic and abdominal cavity) is warranted in the cat or dog presenting with conjunctival melanoma.
Limbal Melanoma
Fig 5. Squamous cell carcinoma (SCC) of the cornea in a middle-aged miniature schnauzer. This dog had a history of chronic keratoconjunctivitis sicca with advanced pigmentary keratitis, both risk factors for corneal SCC. (Courtesy Anne Gemensky, Columbus, OH.)
or cryosurgical ablation of adnexal papillomas is usually curative; however, the development of multiple tumors after excision in some reported cases was suggestive of virus seeding during surgery. = Superficial keratectomy is recommended for excision of corneal papillomas.
Conjunctival Melanoma The conjunctiva of the nictitating membrane 23 and the palpebral x3 and bulbar z4 conjunctiva are common sites of involvement with conjunctival melanomas (Table 1). Lesions appear as raised, solid, and typically darkly pigmented masses. Orbital invasion and metastasis to lymphatics and the lungs have been reported. A direct correlation between the mitotic index and the likelihood of local recurrence or metastasis of the neoplasm is not evident. There is a lack of data on conjunctival melanoma in cats; however, in the few cases reported, the tumors were locally aggressive, 25 and in one series of three cats, conjunctival melanoma was associated with metastasis to regional lymph nodes and diffuse metastasis. 26 Early, wide surgical excision is recommended for melanoma
Tumors of this group are observed as darkly pigmented, solitary, slowly expanding, and nodular epibulbar growths (Table 2). The tumor arises from the dendritic melanocytic cells of the corneoscleral junction, most commonly at the dorsal or dorsolateral limbus 27,z8 (Fig 6). These neoplasms have not been reported to metastasize, but may be locally aggressive, extending into the anterior chamber. Tumors in younger dogs are more likely to be progressive, but in older dogs, growth rate is slower and therapy is often unnecessary. 28,29 Heavily pigmented dogs may be predisposed, and the tumor has been reported more commonly in the German shepherd dog and labrador retriever. 28-3° Limbal melanomas are uncommon in cats, but appear to behave biologically similar to those in dogs. Of six reported cases, 29,31 five limbal melanomas occurred in cats --- 8 years of age. Although the appearance of limbal melanomas in the cat and dog is usually characteristic, scleral extension of an intraocular melanoma (Fig 7) should be ruled out with a complete ophthalmic examination, which may include gonioscopy. Progressive limbal melanomas can be managed with partial to full-thickness corneosclerectomy.28 Partial-thickness defects may be repaired with a conjunctival graft, and full-thickness defects may be repaired with homologous corneoscleral, z8 third eyelid, 32 or synthetic grafts. 33 Cryotherapy,/3-irradiation, laser photoablation, and enucleation are also reported therapies.
Miscellaneous Tumors of the Conjunctiva/Nictitating Membrane Hemangiomas, lipomas, mast cell tumors, and squamous cell carcinoma have been reported in dogs and are all typically
TABLE 1. Biological Behavior of Ocular and Ocular Adnexal Melanoma in Cats and Dogs Tissue
Species
Clinical Appearance
Biological Behavior
Conjunctiva
Canine
Raised, pigmented mass on conjunctiva; third eyelid common site Raised, pigmented mass on bulbar conjunctiva Pigmented, raised mass at limbus; typically dorsal or temporal
Locally aggressive; high potential for local recurrence; potentially metastatic
Feline Limbal
Canine
Anterior Uvea
Feline Canine
Similar to dog Pigmented, raised mass on iris face
Feline
Multifocal to solitary, raised pigment proliferation on iris face
Canine
P~gmented mass in posterior segment
Feline
Pigmented mass in posterior segment
Choroid
OCULAR ONCOLOGY
Similar to dog Slow growing, but potentially locally invasive; increased growth rate in younger versus older dogs Similar to dog Slow growing, locally invasive; low metastatic potential Slow growing with local invasion; high risk for metastasis late in disease process Slow growing, locally invasive with potential for extraocular extension; low metastatic potential Slow growing, locally invasive with potential for extraocular extension; high metastatic potential
79
TABLE 2. Diagnostic Evaluation of the Animal with Suspect Ocular Neoplasia Complete physical examination Complete ophthalmic examination Complete blood count and serum chemistry panel Ocular/orbital ultrasound Thoracic radiography Abdominal radiography/ultrasonography Fine-needle aspiration Enlarged lymph node Orbital mass Suspect metastatic nodule
benign, but they may be locally invasive) 4,35 Angiokeratomas have been reported in dogs. 36,3r These tumors are variable in appearance. Angiokeratomas can be pigmented and resemble conjunctival melanoma. Alternatively, they may be red, raised, and resemble a hemangioma or hemangiosarcoma. Mast cell tumors can affect the canine conjunctiva and nictitans. 3s,39 Intermittent, transient swelling of the affected conjunctiva may be variable owing to mast cell degranulation and histamine release into the affected tissues. The superior palpebral conjunctiva appears to be a predisposed site. Excision was apparently curative in two reported cases. 3s Unfortunately, neither dog was staged for metastatic disease. Adenocarcinoma has been reported in the gland of the nictitating membrane of older dogs. 4° En bloc excision of the third eyelid is an appropriate therapy in such cases, as recurrence of the neoplasm after local excision was reportedly common in this recent series. Fibrosarcoma and adenocarcinoma have been reported to invade the nictitating membrane of cats. 41-43 These neoplasms are malignant and have been associated with metastatic disease. Biopsy of suspect lesions of the conjunctiva and nictitating membrane can be performed with topical anesthesia, often without sedation in an amenable animal. In most cases of confirmed neoplasia involving the third eyelid, the entire tissue should be excised. A diagnostic evaluation for metastatic dis-
Fig 6. Limbal melanoma involving the dorsal limbus in a young, black labrador retriever. As progressive disease is typically anticipated with limbal melanomas in young dogs, this mass was resected and the defect repaired with a homologous tissue graft. 80
ease is warranted in cats with proliferative lesions of the nictitating membrane (Table 2). Uveal Tract
Uveal Melanoma Dogs. Melanocytic tumors of the uveal tract of the dog affect the iris, ciliary body, and choroid (Table 1). Most primary intraocular melanocytic tumors in dogs are benign and histologically resemble limbal melanocytomas, ay There was no breed or sex predilection in one large series, 2y although a predilection for the retrievers and other heavily pigmented breeds has been noted. 44 The appearance of iridociliary melanoma in the dog is variable, but the typical appearance is of a variably raised, heavily pigmented mass lesion on the anterior face of the iris. In dogs, uveal melanomas are locally invasive and ultimately result in loss of vision through the development of secondary glaucoma, retinal detachment, and/or intraocular hemorrhage. 44 Primary choroidal melanomas have been reported in the dog. 45-~8 Choroidal melanomas are likely to be benign, with morphological features identical to those of canine anterior uveal melanomas. Because of their posterior location, choroidal neoplasms are typically not diagnosed until associated ocular disease, resulting from destruction of the local structure, retinal detachment, the development of preiridial fibrovascular membranes, or intraocular hemorrhage occurs. Transscleral extension of choroidal melanoma into the orbit and optic nerve may provide at least the potential for tumor-associated complications after enucleation, 45 although confirmed reports of metastatic choroidal melanomas do not exist in dogs. The apparent rarity of metastasis and unproven efficacy of enucleation in preventing metastasis makes enucleation of normotensive, noninflamed globes containing anterior uveal melanoma difficult to justify. Sector iridectomy of the affected iris is an intraocular surgical option. Noninvasive Nd:YAG 49 and diode laser photocoagulation 44 are considered safe and effective for isolated, pigmented iris masses in dogs.
Fig 7. Extrascleral extension of an iridociliary melanoma in an older Norwegian elkhound. Two sites of tumor extension are apparent both dorsotemporally and dorsomedially. The primary differential diagnosis in this case was a limbal melanoma. WILLIS AND WILKIE
B ~j
@;
Fig 8. (A) Focal involvement of the dorsotemporal iris in a cat with an iris melanoma. Magnified examination of the iris surface revealed a raised, nodular pattern within the pigmented region. (B) Extensive pigmentation of the iris of a cat with diffuse iris melanoma. Exfoliated pigment is present on the surface of the lens within the pupillary space. (Courtesy of Jean Stiles, West Lafayette, IN.)
Cats. Diffuse iris melanoma is the most common primary intraocular neoplasm in the cat. s° This neoplasm typically originates on the anterior surface of the iris, producing multifocal areas of pigmentation with a high potential for local invasion into the ciliary body and the iridocorneal angle sl (Fig 8). Extension posteriorly to affect the choroid is rare. s° Neoplastic cells may infiltrate the adjacent sclera along emissaria and the scleral venous plexus. Common presenting clinical signs in affected cats includes hyperpigmentation of the iris, pupillary deficits, buphthalmia resulting from secondary glaucoma, and evidence of uveitis. 26 Metastatic disease was confirmed in 62.5% of 16 cats with intraocular melanoma reviewed in one series. 26 The regional lymph nodes, liver, and lungs are the principal sites for melanoma metastasis. 26,so Location of neoplastic ceils, extent of ocular involvement, and mitotic index appear to be the most useful morphological features for predicting biological behavior, with no single variable providing definitive prognostic information, so An atypical primary ocular melanoma has been described recently in cats. It originates multifocally from various portions of the uvea other than the iris and progresses to destroy all portions of the globe including the posterior segment, s2 The more posterior origination of these atypical melanomas can result in these tumors being very advanced before becoming externally visible, increasing their metastatic potential, s2 Controversy exists as to the best approach to treatment for cats with uveal melanoma. Results of one study evaluating the survival in cats undergoing enucleation owing to diffuse iris melanoma suggested that those cats with invasion of the ciliary body, stroma, or with glaucoma attributable to tumor infiltration of the ciliary body are likely to die earlier than age-matched control cats. s3 Considering the relatively high metastatic rate of anterior uveal melanoma in cats and the long latency period of metastatic disease, some investigators have advocated early enucleation in affected cats. Iridociliary Epithelial Tumors Uveal adenorna/adenocarcinoma. Primary tumors of the epithelium of the ciliary body and iris occur sporadically in dogs OCULAR ONCOLOGY
and cats. 54-57The clinical features of canine iridociliary tumors can be highly variable owing to the high incidence of secondary ophthalmic conditions such as preiridal fibrovascular membrane development, retinal detachment, uveitis, and glaucoma. Such masses can be pigmented or nonpigmented, solid or papillary, and invasive or noninvasive; they are most commonly derived from the ciliary body epithelium. 58 Papillary tumors with scleral invasion and cellular features of anaplasia are distinguishing features of adenocarcinomas. The golden and labrador retrievers were overrepresented in a recent large review series of iridociliary epithelial tumors in dogs and cats. 5s Medulloepithelioma. Medulloepitheliomas have been reported in young dogs and probably arise from either embryonic neuroepithehum of the optic vesicle or cup during organogenesis or possibly from rests of the same during early neonatal life. 59 These tumors are characterized by the formation of tubular rosettes and primitive neural tissue, and sometimes the ability to differentiate into brain, muscle, or connective tissue elements, s9 There is considerable variation in the relative amounts of each tumor that can be considered malignant. Enucleation is the most common treatment for eyes with iridociliary epithelial tumors and is recommended when evidence of secondary disease is present. There appears to be a low potential for metastasis of adenomas or adenocarcinomas in either species, s~-ss P o s t t r a u m a t i c Sarcoma Posttraumatic sarcomas are malignant primary neoplasms originating in traumatized or chronically inflamed globes of cats. The majority of affected cats have a history of perforating ocular trauma, and lens capsule rupture is commonly observed histologically. 6°,6~ The typical clinical presentation is an older cat with a blind, phthisical eye (Fig 9). Most cats do not exhibit pain or irritation with this neoplasm. 6° Histologically, these tumors tend to infiltrate circumferentially around the inner aspect of the globe. 6° Transcleral extension 61 and optic nerve invasion 6°,61 may occur. The optic nerve may be invaded early in the neoplastic process, and extension of a posttraumatic fibrosarcoma to the optic chiasm was the cause of blindness in 81
an orbital mass suggests the presence of a potentially resectable benign primary orbital neoplasm.
Secondary Ocular Neoplasia The eye and adnexa can be sites of metastasis from distant primary tumors or from local extension of neoplasia involving the periocular skin or the nasal or oral cavities. Multicentric or systemic neoplasia can also manifest in the eye and adnexal tissues, and ocular manifestations are frequently the first sign of such diseases. Systemic Neoplasia
Multicentric Lymphosarcoma (LSA) Fig 9. Posterior synechia, fibrous membranes, a white mass, and a detached retina were identified in this phthisical, blind eye from a cat with a history of ocular trauma. The eye was enucleated and an intraocular posttraumatic sarcoma was identified on histopathology. No lens was identified clinically or histologically, but the sarcoma surrounded what was judged to be lens capsule.
the contralateral eye in one cat. 62 The time between the original traumatic event and the development of this intraocular neoplasm can be from <1 year 63 to >10 years. Metaplastic or neoplastic bone is seen in some globes. 63,64 Enucleation of a blind, phthisical globe in a cat with a history of prior ocular trauma or chronic inflammation is recommended to reduce the risk of extraocular extension of an intraocular sarcoma. Orbit A variety of primary orbital tumors have been reported in cats and dogs and are listed in Table 3. In both species, primary orbital neoplasms are typically malignant. 6,65 Orbital neoplasia should be considered in any chronic, progressive exophthalmia or enophthalmia, 66 especially initially painless processes in older animals. Other clinical signs of orbital neoplasia include chronic conjunctival hyperemia or epiphora, strabismus, and progressive protrusion of the nictitating membrane (Fig 10; Table 4). Differential diagnoses for the clinical signs of orbital neoplasia include orbital cysts, chronic orbital cellulitis or abscess, foreign body reaction, immune-mediated inflammation, and pseudotumor. 67 Differentiating an orbital neoplasm from a nonneoplastic process may be difficult; however, skull radiography and orbital ultrasound may be informative options for evaluating the animal with exophthalmos. In specialty practices, computed tomography and magnetic resonance imaging are superior diagnostic modalities for orbital imaging. Ultrasound-guided, fine-needle aspiration of a well-circumscribed orbital mass may provide cellular material for diagnostic evaluation. Exenteration is typically recommended as palliative therapy for primary orbital neoplasms, particularly in cases where the associated eye is blind or painful owing to the effects of exposure. Intraoperative cryotherapy or postoperative radiation treatment is recommended as adjunctive therapy in cases where malignant orbital tumors are suspected or confirmed with histopathology. Orbitotomy 6s,69 for salvage of a visual eye may be considered when diagnostic imaging and cytologic analysis of 82
Primary ocular LSA has not been documented in humans or animals, but ocular signs may be the initial presentation of this multisystemic disease. 70-72The uveal tract is a common site for metastasis of neoplastic lymphocytes, probably via hematogenous spread. 71~73 Ophthalmic disease was present in 37% of dogs with lymphoma in one prospective study of 94 animals, making ocular disease the most consistent presenting sign of multicentric lymphoma after lymphadenopathy.74 Ophthalmic disease in dogs is most common with lymphoblastic lymphoma and in those with LSA-related hematologic abnormalities. Anterior uveitis and intraocular hemorrhage are the most common manifestations (Table 5); however, infiltration of all ocular structures with neoplastic cells can occur 75 (Fig 11).
TABLE 3. Orbital Tumors in Cats and Dogs
Primary Multilobular tumor of bone Optic nerve meningloma Optic nerve glioma Hemangiosarcoma Mast cell tumor Chondrosarcoma Neurofibrosarcoma Rhabdosarcoma Osteosarcoma Adenocarcinoma Lacrimal gland Zygomatic salivary gland Myxoma/myxosarcoma
Secondary by Extension Adenocarcinoma Nasal cavity Gland of nictitating membrane Squamous cell carcinoma: most common tumor in cats Eyelids Oral cavity Nasal cavity Melanoma Conjunctiva Intraocular (uveal) Eyelid
Secondary by Metastasis Multicentric lymphosarcoma Adenocarcinoma Mammary gland Uterus Kidney Thyroid gland Apocrine sweat gland Melanoma Transitional cell carcinoma Fibrosarcoma Hemangiosarcoma Bronchogenic carcinoma WILLIS AND WILKIE
".,
,
Fig 10. (A) Exophthalmos in an aged cat. Protrusion of the third eyelid, a dilated pupil, and blindness were noted clinically in the left eye. Orbital exenteration revealed an orbital fibrosarcoma. (B) Exophthalmos in a young basset hound. The visual right eye is pushed dorsally by a multilobular tumor of bone involving the orbital bones.
Multiple Myeloma Hyphema, corneal edema, aqueous flare, retinal venous dilation with sacculations or tortuosity, retinal hemorrhages, retinal detachment, and secondary glaucoma have been reported in the eyes of animals with multiple myeloma, z6-Fs In some cases, ophthalmic manifestations are the presenting complaint in affected animals, z9 Ocular signs occur secondary to hyperviscosity, which leads to increased vascular volume and hemorrhagic tendencies, z7 An extramedullary orbital plasmacytoma was identified in a cat with monoclonal gammopathy and acute exophthalmos. The exophthalmos was presumed to be associated with acute orbital bleeding from the tumor that was impinged upon by the mandibular ramus when the cat's owner attempted to medicate the cat orally, so Metastatic N e o p l a s i a Intraocular metastasis from primary tumors at distant sites is uncommon, but varieties have been reported• Animals are often presented for the secondary manifestations of intraocular invasion of neoplastic cells, such as uveitis, hyphema, or secondary glaucoma. Adenocarcinomas have been reported to metastasize to the canine and feline eye. Primary tumors include the adenocarcinomas of the lung, sl m a m m a r y tissue, s2-84 thyroid
TABLE 4. Clinical Signs of Orbital Neoplasia in Dogs and Cats Clinical Sign
Comments
Protrusion of nictitating membrane Resistance to retropulsion of globe Slowly progressive exophthalmos Globe deviation Blindness
Occasional hyperemia/chemosis of conjunctiva
Pupil dilation
OCULAR ONCOLOGY
gland, 82 kidney, s5 pancreas, 82 and uterus. 82 An ischemic chorioretinopathy has recently been described in four cats with angioinvasive bronchogenic carcinoma. 86 Extension of an aural SCC 87 to the orbit and eye was reported in a cat. Hemangiosarcoma, s8 transitional cell carcinoma, s9 pheochromocytoma, 9° seminoma, 9~ fibrosarcoma, 92,93 and melanoma s5,94 have all been reported to metastasize to the eye from distant primary sites. Canine transmissible venereal tumor (TVT) is a disease of low frequency in developed countries, but is endemic in regions of the world with large populations of stray dogs. 95 On rare occasions, TVT, typically located on the external genitalia of both sexes, has metastasized to the eye and associated structures. 95,96 A complete physical examination aimed at identifying a source of primary disease is the key feature of an evaluation of an animal with any inflammatory or hemorrhagic intraocular condition not readily explained by a known trauma or preexisting primary ocular disease. Other diagnostic tests are pursued based on the results of additional clinical signs of disease• In addition, particular attention to the nasal and oral cavities is
TABLE 5. Ophthalmic Manifestations of Systemic Neoplasia Tumor
Ophthalmic Signs
Lymphosarcoma
Anterior uveitis Intraocular hemorrhage hyphema retinal hemorrhage Posterior uveitis PanuveitJs Retinal detachment Uveal mass Pupillary dysfunction, anisocoria, dyscoria Infiltrative keratitis Conjunctwal and third eyelid masses Secondary glaucoma (due to chronic uveitis or cellular infiltration of iridocorneal angle Intraocular hemorrhage hyphema retinal hemorrhage Retinal detachment Anterior uveitis Secondary glaucoma
Enophthalmos reported in cat Direction depends on location of tumor Secondary to optic nerve involvement/ compression Secondary to retinal degeneration or detachment Afferent deficit optic nerve involvement/compression Efferent deficit involvement of parasympathetic nerves to iris
Multiple myeloma
8;3
Fig 11. Neoplastic infiltration of multiple ocular structures in a puppy with multicentric lymphoma. Mass lesions are present in the conjunctiva and the third eyelid. The iris is infiltrated with a mass ventrolaterally, creating a dyscoria of the pupil. Exophthalmos is also present in association with orbital involvement.
warranted to rule out orbital metastasis by local extension (Table 3). In cases of systemic neoplasia, appropriate chemotherapy may cause ocular lesions to regress. However, specific topical therapy may be required to manage intraocular inflammation. Metastatic tumors in the eye are typically managed with enucleation if the owner elects palliative therapy. Enucleation of a painful or blind eye that is resistant to medical therapy in an animal for which systemic or metastatic neoplasia is suspected, but not confirmed, may provide the clinician with valuable diagnostic information.
References 1. Carlton WW: Eyelid neoplasms. In Peiffer RLJ (ed): Comparative Ophthalmic Pathology. Springfield, IL, Charles C. Thomas, 1983, pp 64-86 2. Roberts SM, Severin GA, Lavach JD: Prevalence and treatment of palpebral neoplasms in the dog: 200 cases (1975-1983). J Am Vet Med Assoc 189:1355-1359, 1986 3. Krehbiel JD, Langham RF: Eyelid neoplasms of dogs. Am J Vet Res 36:115-119, 1975 4. Blodi FC, Ramsey FK: Ocular tumors in domestic animals. Am J Ophthalmol 64 (Suppl):627-633, 1967 5, McLaughlin SA, Whitley RD, Gilger BC, et al: Eyelid neoplasms in cats: a review of demographic data (1979-1989). J Am Anim Hosp Assoc 29:63-67, 1993 6. Gilger BC, McLaughlin SA, Whitley RD, et al: Orbital neoplasms in cats: 21 cases (1974-1990). J Am Vet Med Assoc 201:1083-1086, 1992 7. Diters RW, Walsh KM: Feline basal cell tumors: a review of 124 cases. Vet Pathol 21:51-56, 1984 8. Garner FM, Lingeman CH: Mast-call neoplasms of the domestic cat. Path Vet 7:517-530, 1970 9. Moore CP, Constantinescu GM: Surgery of the adnexa. Vet Clin North Am Small Anim Pract 27:1011-1066, 1997 10. Smith MM, Shults S, Waldron DR, et al: Platysma myocutaneous flap for head and neck reconstruction in cats. Head Neck 15:443-449, 1993 11. Pavletic MM, Nafa LA, Confer AW: Mucocutaneous subdermal plexus flap from the lip for lower eyelid restoration in the dog. J Am Vet Med Assoc 180:921-926, 1982 12. Lawson DD: Corneal dermoids in animals. Vet Rec 97:449-450, 1975 84
13. Hendy-lbbs PM: Familial feline epibulbar dermoids. Vet Rec 116:1314, 1985 14. Bernays ME, Flemming D, Peiffer RL Jr: Primary corneal papilloma and squamous cell carcinoma associated with pigmentary keratitis in four dogs. J Am Vet Med Assoc 214:215-217, 1999 15. Latimer KS, Kaswan RL, Sundberg JP: Corneal squamous cell carcinoma in a dog. J Am Vet Med Assoc 190:1430-1432, 1987 16. Hargis AM, Lee AC, Thomassen RW: Tumor and tumor-like lesions of perilimbal conjunctiva in laboratory dogs. J Am Vet Med Assoc 173:1185-1190, 1978 17. Ward DA, Latimer KS, Askren RM: Squamous cell carcinoma of the corneoscleral limbus in a dog. J Am Vet Med Assoc 200:1503-1506, 1992 18. Bonney CH, Koch SA, Dice PF, et al: Papillomatosis of conjunctiva and adnexa in dogs. J Am Vet Med Assoc 176:48-51, 1980 19. Bonney CH, Koch SA, Confer AW, et al: A case report: a conjunctivocorneal papilloma with evidence of a viral etiology. J Small Anita Pract 21:183-188, 1980 20. Tokita H, Konishi S: Studies on canine oral papillomatosis. II. Oncogenicity of canine oral papilloma virus to various tissues of dog with special reference to eye tumor. Nippon J uigaku Zasshi 37:109-120, 1975 21. Glaze MB, Gelatt KN: Feline ophthalmology, in Gelatt KN (ed): Veterinary Ophthalmology (3rd Ed) Philadelphia: Lippincott, Williams & Wilkins, 1999, pp 997-1052 22. Collier LL, Collins BK: Excision and cryosurgical ablation of severe periocular papillomatosis in a dog [clinical conference]. J Am Vet Med Assoc 204:881-883; discussion 884-885, 1994 23. Collins BK, Collier LL, Miller MA, et al: Biological behavior and histologic characteristics of canine conjunctival melanoma. Prog Vet Comp Ophthalmol 3:135-140, 1993 24. Belkin PV: Malignant melanoma of the bulbar conjunctiva in a dog. Vet Med Small Anim Clin 70:957-958, 1975 25. Cook CS, Rosencrantz W, Peiffer RL, et al: Malignant melanoma of the conjunctiva in a cat. J Am Vet Med Assoc 186:505-506, 1985 26. Patnaik AK, Mooney S: Feline melanoma: a comparative study of ocular, oral, and dermal neoplasms. Vet Pathol 25:105-112, 1988 27. Wilcock BP, Peiffer RL Jr: Morphology and behavior of primary ocular melanomas in 91 dogs. Vet Pathol 23:418-424, 1986 28. Martin CL: Canine epibulbar melanomas and their management. J Am Anim Hosp Assoc 17:83-90, 1981 29. Sullivan TC, Nasisse MP, Davidson MG, et al: Photocoagulation of limbal melanoma in dogs and cats: 15 cases (1989-1993). J Am Vet Med Assoc 208:891-894, 1996 30. Giuliano EA, Chappell R, Fischer B, et al: A matched observational study of canine survival with primary intraocular melanocytic neoplasia. Vet Ophthalmol 2:185-190, 1999 31. Harling DE, Peiffer RL, Cook CS, et al: Feline limbal melanomas: four cases. J Am Anim Hosp Assoc 22:795-802, 1986 32. Blogg JR, Dutton AG, Stanley RG: Use of third eyelid grafts to repair full thickness defects in the cornea and sclera. J Am Anim Hosp Assoc 25:505-512, 1989 33. Wilkie DA, Wolf ED: Treatment of epibulbar melanocytoma in a dog, using full-thickness eyewall resection and synthetic graft. J Am Vet Med Assoc 198:1019-1022, 1991 34. Peiffer RLJ, Duncan J, Terrel T: Hemangioma of the nictitating membrane of a dog. J Am Vet Med Assoc 172:832-833, 1978 35. Lavach JD, Snyder SP: Squamous cell carcinoma of the third eyelid in a dog. J Am Vet Med Assoc 184:975-976, 1984 36. George C, Summers BA: Angiokeratoma: a benign vascular tumor of the dog. J Small Anim Pract 31:390-392, 1990 87. Buyukmihci N, Stannard BA: Canine conjunctival angiokeratomas. J Am Vet Med Assoc 178:1279-1282, 1981 38. Johnson BW, Bnghtman AH, Whitely HE: Conjunctival mast cell tumor in two dogs. J Am Anim Hosp Assoc 24:439-442, 1988 39. Halstrom M: Mastocytoma of the third eyelid of a dog. J Small Anita Pract 11:469-472, 1970 40. Wilcock B, Peiffer RLJ: Adenocarcinoma of the gland of the third eyelid in seven dogs. J Am Vet Med Assoc 193:1549-1550, 1988 41. Komaromy AM, Ramsey DT, Render JA, et al: Primary adenocarcinoma of the gland of the nictitating membrane in a cat. J Am Anim Hosp Assoc 33:333-336, 1997 42. Williams LW, Gelatt KN, Gwin RM: Ophthalmic neoplasms in the cat. J Am Anim Hosp Assoc 17:999-1008, 1981 WILLIS AND WlLKIE
43. Buyukmihci N: Fibrosarcoma of the nictitating membrane in a cat. J Am Vet Med Assoc 1975:934-935, 1975 44. Cook CS, Wilkie DA: Treatment of presumed iris melanoma in dogs by diode laser photocoagulation: 23 cases. Vet Ophthalmol 2:217225, 1999 45. Colhson PN, Peiffer RL: Clinical presentation, morphology, and behavior of primary choroidal melanomas in eight dogs. Prog Vet Comp Ophthalmol 3:158-164, 1993 46. Schoster JV, Dubielzig RR, Sullivan L: Choroidal melanoma in a dog. J Am Vet Med Assoc 203:89-91, 1993 47. Aguirre GD, Brown G, Shields JA, et al: Melanoma of the choroid in a dog. J Am Anim Hosp Assoc 20:471-476, 1984 48. Dubielzig RR, Aguirre GD, Gross SL, et al: Choroidal melanomas in dogs. Vet Pathol 22:582-585, 1985 49. Nasisse MP, Davidson MG, Olivero DK, et al: Neodymium:YAG laser treatment of primary canine intraocular tumors. Prog Vet Comp Ophthalmol 3:152-157, 1993 50. Duncan DE, Peiffer RL: Morphology and prognostic indicators of anterior uveal melanomas in cats. Prog Vet Comp Ophthalmol 1:2532, 1991 51. Acland GM, McLean IW, Aguirre GD, et al: Diffuse iris melanoma in cats. J Am Vet Med Assoc 176:52-56, 1980 52. Harris BP, Dubielzig RR: Atypical primary ocular melanoma in cats. Vet Ophthalmol 2:121-124, 1999 53. Kalishman JB, Chappell R, Flood LA, et al: A matched observational study of survival in cats with enucleation due to diffuse tns melanoma. Vet Ophthalmol 1:25-29, 1998 54. Peiffer RL Jr, Gwin RM, Gelatt KN, et al: Ciliary body epithelial tumors in four dogs. J Am Vet Med Assoc 172:578-583, 1978 55. Peiffer RL: Ciliary body epithelial tumors in the dog and cat: a report of 13 cases. J Small Anim Pract 24:347-370, 1983 58. Bellhorn RW: Ciliary body adenocarcinoma in the dog. J Am Vet Med Assoc 159:1124-1128, 1971 57. Bellhom RW, Henkind P: Adenocarcinoma of the ciliary body. A report of 2 cases in dogs. Pathol Vet 5:122-126, 1968 58. Dubielzig RR, Steinberg H, Garvin H, et al: Iridociliary epithelial tumors in 100 dogs and 17 cats: a morphological study. Vet Ophthalmol 1:223-231, 1998 59. Langloss JM, Zimmerman LE, Krehibiel JD: Malignant intraocular teratoid medulloepithelioma in three dogs. Vet Pathol 13:343-352, 1976 60. Dubielzig RR, Everitt J, Shadduck JA, et al: Clinical and morphologic features of post-traumatic ocular sarcomas in cats. Vet Pathol 27: 62-65, 1990 61. Cullen CL, Haines DM, Jackson ML, et al: The use of immunohistochemistry and the polymerase chain reaction for detection of feline leukemia virus and feline sarcoma virus in six cases of fehne ocular sarcoma. Vet Ophthalmol 1:189-193, 1998 62. Barrett PM, Merideth RE, Alarcon FL: Central amaurosis induced by an intraocular, posttraumatic fibrosarcoma in a cat. J Am Anim Hosp Assoc 31:242-245, 1995 63. Dubielzig RR: Ocular sarcoma following trauma in three cats. J Am Vet Med Assoc 184:578-581, 1984 64. Woog J, Albert DM, Gender JR, et al: Osteosarcoma in a phthisical feline eye. Vet Pathol 20:209-214, 1983 65. Kern TJ: Orbital neoplasia in 23 dogs. J Am Vet Med Assoc 186:489491, 1985 66. Pentlarge VW, PowelI-Johnson G, Martin CL, et al: Orbital neoplasia wtth enophthalmos in a cat. J Am Vet Med Assoc 195:1249-1251, 1989 67. Miller SA, van der Weerdt A, Bartick TE: Retrobulbar pseudotumor of the orbit in a cat. J Am Vet Med Assoc 216:356-358, 2000 68. Slatter DH, Abdelbaki Y: Lateral orbitotomy by zygomatic arch resection in the dog. J Am Vet Med Assoc 175:1179-1182, 1979 69. Gilger BC, Whttley RD, McLaughlin SA: Modified lateral orbitotomy for removal of orbital neoplasms in two dogs. Vet Surg 23:53-58, 1994 70. Schachat AP, Markowitz JA, Guyer DR, et al: Ophthalmic manifestations of leukemia. Arch Ophthalmol 107:697-701, 1989
OCULAR ONCOLOGY
71. Saunders LZ, Barren CN: Intraocular tumors in animals. IV. Lymphosarcoma. Br Vet J 120:25-35, 1964 72. Cocoran KA, Peiffer RL, Koch SA: Histopathologic features of feline ocular lymphosarcoma: 49 cases (1978-1992). Vet Comp Qphthalmol 5:113-116, 1995 73. Kilrain CG, Saik JE, Jeglum KA: Malignant angioendotheliomatosis with retinal detachments in a dog. J Am Vet Med Assoc 204:918-921, 1994 74. Krohne SG, Henderson NM, Richardson RC, et al: Prevalence of ocular involvement in dogs with multicentric lymphoma: prospective evaluation of 94 cases. Vet Comp Ophthalmol 4:127-135, 1994 75. Habin DJ, Else RW: Parotid salivary gland adenocarcinoma with bilateral ocular and osseous metastases in a dog. J Small Anim Pract 36:445-449, 1995 76. Kirschner SE, Niyo Y, Hill BL, et al: Blindness in a dog with IgAforming myeloma. J Am Vet Med Assoc 193:349-350, 1988 77. Center SA, Smith JF: Ocular lesions in a dog with serum hyperviscosity secondary to an IgA myeloma. J Am Vet Med Assoc 181:811 813, 1982 78. err CM, Higginson J, Baker JR, et al: Plasma cell myeloma with igG paraproteinemia in a bitch. J Small Anita Pract 22:31-37, 1981 79. Hendrix DV, Gelatt KN, Smith PJ, et al: Ophthalmic disease as the presenting complaint in five dogs with multiple myeloma. J Am Anim Hosp Assoc 34:121-128, 1998 80. Ward DA, McEntee MF, Weddle DL: Orbital plasmacytoma tn a cat. J Small Anim Pract 38:576-578, 1997 81. Gionfroddo JR, Fix AS, Niyo Y, et al: Ocular manifestations of a metastatic pulmonary adenocarcinoma in a cat. J Am Vet Med Assoc 197:372-374, 1990 82. Bellhorn RW: Secondary ocular adenocarcinoma in three dogs and a cat. J Am Vet Med Assoc 160:302-307, 1972 83. Ladds PW, Gelatt KN, Strafuss AC, et al: Canine ocular adenocarcinema of mammary origin. J Am Vet Med Assoc 156:63-69, 1970 84. West CS, Wolf ED, Vanisi SJ: Intraocular metastasis of mammary adenocarcinoma in the cat. J Am Anim Hosp Assoc 15:725-728, 1979 85. Barren CN, Saunders LZ, Jubb KV: Intraocular tumors in animals. Ill. Secondary intraocular tumors. Am J Vet Res 24:835-853, 1963 86. Cassotis NJ, Dubielzig RR, Gilger BC, et al; Angioinvasive pulmonary carcinoma with posterior segment metastasis in four cats. Vet Ophthalmol 2:125-131, 1999 87. Hayden DW: Squamous celt carcinoma in a cat with intraocular and orbital metastases. Vet Pathol 13:332-336, 1976 88. Szymanski CM: Bilateral metastic intraocular hemangiosarcoma in a dog. J Am Vet Med Assoc 161:803-805, 1972 89. Szymanskt C, Boyce R, Wyman M: Transitional cell carcinoma of the urethra metastattc to the eyes in a dog. J Am Vet Med Assoc 185:1003-1004, 1984 90. Nyska A, Hermalin A, Jakobson B, et al: Intraocular vascular embolization of a malignant canine pheochromocytoma. Prog Vet Comp Ophthalmol 2:129-132, 1992 91. HogenEsch H, Whiteley HE, Vicini DS, et al: Seminoma with metastases in the eyes and the brain in a dog. Vet Patho124:278-280, 1987 92. Lavach JD: Disseminated neoplasia presenting with ocular signs: a report of two cases. J Am Anim Hosp Assoc 20:459-462, 1984 93. Fulton LM, Bromberg NM, Goldschmidt MH: Soft tissue fibrosarcoma with intraocular metastasis in a cat. Prog Vet Comp Ophthalmol 1:129-132, 1991 94. Brodey RS, Pflugfelder C, MJkkilineni S, et al: Clinico-pathologic conference: a 6-year-old German shepherd dog with a rapid growing mass in the left popliteal fossa. J Am Vet Med Assoc 172:837-841, 1978 95. Boscos CM, Ververidis HN, Tondis DK, et al: Ocular involvement of transmissible venereal tumor in a dog. Vet Ophthalmol 1:167-170, 1998 96. Daas LL, Sahay PN, Khan AA, et al: Malignant transmissible veneral tumor. Canine Pract 13:15-18, 1986
85
Neoplasia can affect all ocular tissues. The clinical appearance of ocular neoplasia can vary considerably depending on the specific tissue involved. Intraocular neoplasia may mimic or incite ocular inflammatory disease in addition to causing hyphema or secondary glaucoma. Intraocular neoplasms can be primary tumors or may be secondary to metastatic disease or systemic neoplasia. Primary neoplasms, metastatic tumors, tumors extending from adjacent structures, and systemic neoplasms can also affect the adnexal tissues. Many ophthalmic tumors are histologically benign but are locally invasive and, within the confined space of the eye or orbit, can produce significant tissue distortion. Certain ocular neoplasms, such as many canine eyelid tumors, are amenable to simple excision and can be adequately managed in general practice. The evaluation and treatment of other ophthalmic neoplasms, however, may require the additional equipment available only in larger specialty practices, such as computed tomography and radiation therapy. Early diagnosis of ocular neoplasia is an important aspect of successful management. Copyright © 2001 by W.B. Saunders Company
lthough neoplasia uncommonly affects the eyes of companion animals, it should be included on the differential lists for diseases affecting all ocular tissues. Prompt diagnosis of ocular neoplasia is paramount for successful management. This article reviews primary tumors of the eye and ocular adnexa in both cats and dogs as well as secondary tumors that have been reported to metastasize to the dog and cat eye.
A
Primary
Ocular Neoplasia Eyelids
Neoplasms in the eyelids are relatively common in dogs. Eyelid neoplasms are similar to those that occur in the skin generally and arise from epithelial, mesenchymal, and melanogenic cells, i Sebaceous gland tumors, squamous papillomas, and melanomas occur with high frequency in the eyelids of dogs 2,3 and tend to be benign, although progressive growth can be associated with ocular surface irritation. Sebaceous gland tumors generally arise in the eyelids from the meibomian glands and include sebaceous adenoma, sebaceous epithelioma, and sebaceous adenocarcinoma. 1 These tumors present as raised, variably sized, and sometimes pigmented masses (Fig 1). Other less common neoplasms affecting the canine eyelid include basal From the Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, OH. Address reprint requests to A. Michelle Willis, DVM, Rowley Memorial Animal Hospital, 171 Union Street, Springfield, MA 01105. E-mail: [email protected] Copyright © 2001 by W.B. Saunders Company 1096-2867/01/1601-0010535.00/0 doi:10.1053/svms.2001.22810
cell epitheliomas 2-* and basal cell carcinomas (Fig 2), fibromas, fibrosarcoma, neurofibroma, and neurofibrosarcoma. Cutaneous histiocytomas occasionally affect the canine eyelid. Their appearance is characterized by a smooth, hairless, pink exterior with a typically sessile base (Fig 3). This tumor is most often seen in young dogs and is amenable to surgical resection, as they can sometimes be locally invasive but often resolve spontaneously. Primary eyelid neoplasms are rare in cats. Squamous cell carcinoma (SCC) was the most common eyelid neoplasm reported in one series. 5 In this series eyehd neoplasia in general and specifically SCC was most frequent in cats 10 years of age or older. Eyelid SCC usually presents as a proliferative pink to white mass or as a progressive, ulcerated lesion (Fig 4). The medial canthal eyelid is frequently initially affected, and white cats are predisposed. Eyelid SCC has also been reported to metastasize to the orbit. 6 Basal cell carcinoma, 7 mast cell tumor, 8 and fibrosarcoma have also been reported in cats with relatively high frequency.
Diagnosis and Therapy Fine-needle aspiration of an atypical eyelid mass may be helpful from a prognostic standpoint, but in general, surgical removal with full-thickness excision and two-layer closure is recommended if the mass is irritating, undergoes an overt growth rate change, or is prone to bleeding. Up to one third of the length of the lid margin may be removed in a dog with a normal palpebral fissure length. Larger lesions may require wider excision and more extensive surgical reconstruction of the defect. 9-1] Cyrotherapy, hyperthermia, radiation, laser photocoagulation, or local and adjunctive systemic chemotherapy may be effective in the management of specific tumors, particularly those that do not lend themselves to complete surgical excision because of location and extent. Cornea, Sclera, Conjunctiva, and Nictitating M e m b r a n e
Dermoids Dermoids are choristomas that usually develop on the conjunctiva and cross the limbus to involve the cornea; they have been reported in both dogs and cats. 12,13 These congenital tumors can contain keratinized epithelium, fibrous tissue, hair, fat, blood, vessel, nerves, glands, smooth muscle, and cartilage. Hair is usually evident in corneal dermoids, and the corneal irritation induced by long, stiff hairs usually warrants intervention. Treatment is by surgical excision with superficial keratectomy/conj unctivectomy. Squamous Cell Carcinoma Several cases of corneal SCC reported in dogs occurred in eyes with advanced pigmentary keratitis, a condition that commonly
Clinical Techniques in Small Animal Practice, Vol 16, No 1 (February), 2001: pp 77-85
77
Fig 3. Histiocytoma of the lower eyelid in a young labrador retriever. The smooth, hairless appearance is typical for cutaneous histiocytoma; however, the diagnosis was confirmed with cytology acquired by fine-needle aspiration. The mass in this dog spontaneously regressed approximately 2 weeks after presentation.
(Fig 5). The tendency to metastasize appears to be rare, based on an absence of reports in the literature. Superficial keratectomy of a corneal lesion may be curative; however, adjunctive therapy with cryosurgery or /3-radiation (commonly strontium90) may reduce local recurrence rate. Addressing the un&flying source of chronic irritation, where applicable, is an important aspect of therapy. Fig 1. Sebaceous adenoma involving the lower eyelid of a middle-aged dog. The orientation of the mass resulted in corneal contact as it grew, inducing intermittent epiphora and blepharospasm.
Papilloma
accompanies chronic corneal irritation. ~4-16 Canine corneal SCC has been associated with chronic keratoconjunctivitis sicca, ~r or keratitis secondary to enophthalmos. ~5 Chronic irritation or trauma to tissues may induce tumor development, 15 so ocular tumors and pigmentary keratitis may share risk factors. > Corneal SCC is characterized by a pink, typically irregular mass protruding from the epithelial surface of the cornea
Papillomas have been described in the canine conjunctiva, the eyelid, and the cornea. 18,19 Corneal papillomas are typically slow-growing and benign and have been seen in association with pigmentary keratitis 1~ but is more typically related to papillomavirus infection in dogs. 18-2° Cutaneous papillomas are rare feline tumors that appear clinically as well-circumscribed, pedunculated, alopecic masses that may involve the eyelid. 2~ Ocular papillomas may spontaneously regress, ~8 however, if the masses are locally irritating, removal is warranted. Excision
Fig 2. Basal cell carcinoma of the superior eyelid of an aged basset hound. The local but extensive invasion of the neoplasm necessitated enucleation. (Courtesy of Jean Stiles, West Lafayette, IN.)
Fig 4. Squamous cell carcinoma (SCC) involving the lower and upper eyelids in an older, white cat. Surface ulceration is typical for SCC at this site.
78
WILLIS AND WILKIE
of the conjunctiva in both cats and dogs. Multiple recurrences, necessitating enucleation, have been reported in both species. 23-26 Adjunctive cryotherapy may reduce the risk of local recurrence due to incomplete excision, as neoplastic cells were identified at the surgical margins of several cases thought to be completely excised by the attending surgeon. 23 Preoperauve evaluation for metastatic disease (regional lymph nodes, thoracic and abdominal cavity) is warranted in the cat or dog presenting with conjunctival melanoma.
Limbal Melanoma
Fig 5. Squamous cell carcinoma (SCC) of the cornea in a middle-aged miniature schnauzer. This dog had a history of chronic keratoconjunctivitis sicca with advanced pigmentary keratitis, both risk factors for corneal SCC. (Courtesy Anne Gemensky, Columbus, OH.)
or cryosurgical ablation of adnexal papillomas is usually curative; however, the development of multiple tumors after excision in some reported cases was suggestive of virus seeding during surgery. = Superficial keratectomy is recommended for excision of corneal papillomas.
Conjunctival Melanoma The conjunctiva of the nictitating membrane 23 and the palpebral x3 and bulbar z4 conjunctiva are common sites of involvement with conjunctival melanomas (Table 1). Lesions appear as raised, solid, and typically darkly pigmented masses. Orbital invasion and metastasis to lymphatics and the lungs have been reported. A direct correlation between the mitotic index and the likelihood of local recurrence or metastasis of the neoplasm is not evident. There is a lack of data on conjunctival melanoma in cats; however, in the few cases reported, the tumors were locally aggressive, 25 and in one series of three cats, conjunctival melanoma was associated with metastasis to regional lymph nodes and diffuse metastasis. 26 Early, wide surgical excision is recommended for melanoma
Tumors of this group are observed as darkly pigmented, solitary, slowly expanding, and nodular epibulbar growths (Table 2). The tumor arises from the dendritic melanocytic cells of the corneoscleral junction, most commonly at the dorsal or dorsolateral limbus 27,z8 (Fig 6). These neoplasms have not been reported to metastasize, but may be locally aggressive, extending into the anterior chamber. Tumors in younger dogs are more likely to be progressive, but in older dogs, growth rate is slower and therapy is often unnecessary. 28,29 Heavily pigmented dogs may be predisposed, and the tumor has been reported more commonly in the German shepherd dog and labrador retriever. 28-3° Limbal melanomas are uncommon in cats, but appear to behave biologically similar to those in dogs. Of six reported cases, 29,31 five limbal melanomas occurred in cats --- 8 years of age. Although the appearance of limbal melanomas in the cat and dog is usually characteristic, scleral extension of an intraocular melanoma (Fig 7) should be ruled out with a complete ophthalmic examination, which may include gonioscopy. Progressive limbal melanomas can be managed with partial to full-thickness corneosclerectomy.28 Partial-thickness defects may be repaired with a conjunctival graft, and full-thickness defects may be repaired with homologous corneoscleral, z8 third eyelid, 32 or synthetic grafts. 33 Cryotherapy,/3-irradiation, laser photoablation, and enucleation are also reported therapies.
Miscellaneous Tumors of the Conjunctiva/Nictitating Membrane Hemangiomas, lipomas, mast cell tumors, and squamous cell carcinoma have been reported in dogs and are all typically
TABLE 1. Biological Behavior of Ocular and Ocular Adnexal Melanoma in Cats and Dogs Tissue
Species
Clinical Appearance
Biological Behavior
Conjunctiva
Canine
Raised, pigmented mass on conjunctiva; third eyelid common site Raised, pigmented mass on bulbar conjunctiva Pigmented, raised mass at limbus; typically dorsal or temporal
Locally aggressive; high potential for local recurrence; potentially metastatic
Feline Limbal
Canine
Anterior Uvea
Feline Canine
Similar to dog Pigmented, raised mass on iris face
Feline
Multifocal to solitary, raised pigment proliferation on iris face
Canine
P~gmented mass in posterior segment
Feline
Pigmented mass in posterior segment
Choroid
OCULAR ONCOLOGY
Similar to dog Slow growing, but potentially locally invasive; increased growth rate in younger versus older dogs Similar to dog Slow growing, locally invasive; low metastatic potential Slow growing with local invasion; high risk for metastasis late in disease process Slow growing, locally invasive with potential for extraocular extension; low metastatic potential Slow growing, locally invasive with potential for extraocular extension; high metastatic potential
79
TABLE 2. Diagnostic Evaluation of the Animal with Suspect Ocular Neoplasia Complete physical examination Complete ophthalmic examination Complete blood count and serum chemistry panel Ocular/orbital ultrasound Thoracic radiography Abdominal radiography/ultrasonography Fine-needle aspiration Enlarged lymph node Orbital mass Suspect metastatic nodule
benign, but they may be locally invasive) 4,35 Angiokeratomas have been reported in dogs. 36,3r These tumors are variable in appearance. Angiokeratomas can be pigmented and resemble conjunctival melanoma. Alternatively, they may be red, raised, and resemble a hemangioma or hemangiosarcoma. Mast cell tumors can affect the canine conjunctiva and nictitans. 3s,39 Intermittent, transient swelling of the affected conjunctiva may be variable owing to mast cell degranulation and histamine release into the affected tissues. The superior palpebral conjunctiva appears to be a predisposed site. Excision was apparently curative in two reported cases. 3s Unfortunately, neither dog was staged for metastatic disease. Adenocarcinoma has been reported in the gland of the nictitating membrane of older dogs. 4° En bloc excision of the third eyelid is an appropriate therapy in such cases, as recurrence of the neoplasm after local excision was reportedly common in this recent series. Fibrosarcoma and adenocarcinoma have been reported to invade the nictitating membrane of cats. 41-43 These neoplasms are malignant and have been associated with metastatic disease. Biopsy of suspect lesions of the conjunctiva and nictitating membrane can be performed with topical anesthesia, often without sedation in an amenable animal. In most cases of confirmed neoplasia involving the third eyelid, the entire tissue should be excised. A diagnostic evaluation for metastatic dis-
Fig 6. Limbal melanoma involving the dorsal limbus in a young, black labrador retriever. As progressive disease is typically anticipated with limbal melanomas in young dogs, this mass was resected and the defect repaired with a homologous tissue graft. 80
ease is warranted in cats with proliferative lesions of the nictitating membrane (Table 2). Uveal Tract
Uveal Melanoma Dogs. Melanocytic tumors of the uveal tract of the dog affect the iris, ciliary body, and choroid (Table 1). Most primary intraocular melanocytic tumors in dogs are benign and histologically resemble limbal melanocytomas, ay There was no breed or sex predilection in one large series, 2y although a predilection for the retrievers and other heavily pigmented breeds has been noted. 44 The appearance of iridociliary melanoma in the dog is variable, but the typical appearance is of a variably raised, heavily pigmented mass lesion on the anterior face of the iris. In dogs, uveal melanomas are locally invasive and ultimately result in loss of vision through the development of secondary glaucoma, retinal detachment, and/or intraocular hemorrhage. 44 Primary choroidal melanomas have been reported in the dog. 45-~8 Choroidal melanomas are likely to be benign, with morphological features identical to those of canine anterior uveal melanomas. Because of their posterior location, choroidal neoplasms are typically not diagnosed until associated ocular disease, resulting from destruction of the local structure, retinal detachment, the development of preiridial fibrovascular membranes, or intraocular hemorrhage occurs. Transscleral extension of choroidal melanoma into the orbit and optic nerve may provide at least the potential for tumor-associated complications after enucleation, 45 although confirmed reports of metastatic choroidal melanomas do not exist in dogs. The apparent rarity of metastasis and unproven efficacy of enucleation in preventing metastasis makes enucleation of normotensive, noninflamed globes containing anterior uveal melanoma difficult to justify. Sector iridectomy of the affected iris is an intraocular surgical option. Noninvasive Nd:YAG 49 and diode laser photocoagulation 44 are considered safe and effective for isolated, pigmented iris masses in dogs.
Fig 7. Extrascleral extension of an iridociliary melanoma in an older Norwegian elkhound. Two sites of tumor extension are apparent both dorsotemporally and dorsomedially. The primary differential diagnosis in this case was a limbal melanoma. WILLIS AND WILKIE
B ~j
@;
Fig 8. (A) Focal involvement of the dorsotemporal iris in a cat with an iris melanoma. Magnified examination of the iris surface revealed a raised, nodular pattern within the pigmented region. (B) Extensive pigmentation of the iris of a cat with diffuse iris melanoma. Exfoliated pigment is present on the surface of the lens within the pupillary space. (Courtesy of Jean Stiles, West Lafayette, IN.)
Cats. Diffuse iris melanoma is the most common primary intraocular neoplasm in the cat. s° This neoplasm typically originates on the anterior surface of the iris, producing multifocal areas of pigmentation with a high potential for local invasion into the ciliary body and the iridocorneal angle sl (Fig 8). Extension posteriorly to affect the choroid is rare. s° Neoplastic cells may infiltrate the adjacent sclera along emissaria and the scleral venous plexus. Common presenting clinical signs in affected cats includes hyperpigmentation of the iris, pupillary deficits, buphthalmia resulting from secondary glaucoma, and evidence of uveitis. 26 Metastatic disease was confirmed in 62.5% of 16 cats with intraocular melanoma reviewed in one series. 26 The regional lymph nodes, liver, and lungs are the principal sites for melanoma metastasis. 26,so Location of neoplastic ceils, extent of ocular involvement, and mitotic index appear to be the most useful morphological features for predicting biological behavior, with no single variable providing definitive prognostic information, so An atypical primary ocular melanoma has been described recently in cats. It originates multifocally from various portions of the uvea other than the iris and progresses to destroy all portions of the globe including the posterior segment, s2 The more posterior origination of these atypical melanomas can result in these tumors being very advanced before becoming externally visible, increasing their metastatic potential, s2 Controversy exists as to the best approach to treatment for cats with uveal melanoma. Results of one study evaluating the survival in cats undergoing enucleation owing to diffuse iris melanoma suggested that those cats with invasion of the ciliary body, stroma, or with glaucoma attributable to tumor infiltration of the ciliary body are likely to die earlier than age-matched control cats. s3 Considering the relatively high metastatic rate of anterior uveal melanoma in cats and the long latency period of metastatic disease, some investigators have advocated early enucleation in affected cats. Iridociliary Epithelial Tumors Uveal adenorna/adenocarcinoma. Primary tumors of the epithelium of the ciliary body and iris occur sporadically in dogs OCULAR ONCOLOGY
and cats. 54-57The clinical features of canine iridociliary tumors can be highly variable owing to the high incidence of secondary ophthalmic conditions such as preiridal fibrovascular membrane development, retinal detachment, uveitis, and glaucoma. Such masses can be pigmented or nonpigmented, solid or papillary, and invasive or noninvasive; they are most commonly derived from the ciliary body epithelium. 58 Papillary tumors with scleral invasion and cellular features of anaplasia are distinguishing features of adenocarcinomas. The golden and labrador retrievers were overrepresented in a recent large review series of iridociliary epithelial tumors in dogs and cats. 5s Medulloepithelioma. Medulloepitheliomas have been reported in young dogs and probably arise from either embryonic neuroepithehum of the optic vesicle or cup during organogenesis or possibly from rests of the same during early neonatal life. 59 These tumors are characterized by the formation of tubular rosettes and primitive neural tissue, and sometimes the ability to differentiate into brain, muscle, or connective tissue elements, s9 There is considerable variation in the relative amounts of each tumor that can be considered malignant. Enucleation is the most common treatment for eyes with iridociliary epithelial tumors and is recommended when evidence of secondary disease is present. There appears to be a low potential for metastasis of adenomas or adenocarcinomas in either species, s~-ss P o s t t r a u m a t i c Sarcoma Posttraumatic sarcomas are malignant primary neoplasms originating in traumatized or chronically inflamed globes of cats. The majority of affected cats have a history of perforating ocular trauma, and lens capsule rupture is commonly observed histologically. 6°,6~ The typical clinical presentation is an older cat with a blind, phthisical eye (Fig 9). Most cats do not exhibit pain or irritation with this neoplasm. 6° Histologically, these tumors tend to infiltrate circumferentially around the inner aspect of the globe. 6° Transcleral extension 61 and optic nerve invasion 6°,61 may occur. The optic nerve may be invaded early in the neoplastic process, and extension of a posttraumatic fibrosarcoma to the optic chiasm was the cause of blindness in 81
an orbital mass suggests the presence of a potentially resectable benign primary orbital neoplasm.
Secondary Ocular Neoplasia The eye and adnexa can be sites of metastasis from distant primary tumors or from local extension of neoplasia involving the periocular skin or the nasal or oral cavities. Multicentric or systemic neoplasia can also manifest in the eye and adnexal tissues, and ocular manifestations are frequently the first sign of such diseases. Systemic Neoplasia
Multicentric Lymphosarcoma (LSA) Fig 9. Posterior synechia, fibrous membranes, a white mass, and a detached retina were identified in this phthisical, blind eye from a cat with a history of ocular trauma. The eye was enucleated and an intraocular posttraumatic sarcoma was identified on histopathology. No lens was identified clinically or histologically, but the sarcoma surrounded what was judged to be lens capsule.
the contralateral eye in one cat. 62 The time between the original traumatic event and the development of this intraocular neoplasm can be from <1 year 63 to >10 years. Metaplastic or neoplastic bone is seen in some globes. 63,64 Enucleation of a blind, phthisical globe in a cat with a history of prior ocular trauma or chronic inflammation is recommended to reduce the risk of extraocular extension of an intraocular sarcoma. Orbit A variety of primary orbital tumors have been reported in cats and dogs and are listed in Table 3. In both species, primary orbital neoplasms are typically malignant. 6,65 Orbital neoplasia should be considered in any chronic, progressive exophthalmia or enophthalmia, 66 especially initially painless processes in older animals. Other clinical signs of orbital neoplasia include chronic conjunctival hyperemia or epiphora, strabismus, and progressive protrusion of the nictitating membrane (Fig 10; Table 4). Differential diagnoses for the clinical signs of orbital neoplasia include orbital cysts, chronic orbital cellulitis or abscess, foreign body reaction, immune-mediated inflammation, and pseudotumor. 67 Differentiating an orbital neoplasm from a nonneoplastic process may be difficult; however, skull radiography and orbital ultrasound may be informative options for evaluating the animal with exophthalmos. In specialty practices, computed tomography and magnetic resonance imaging are superior diagnostic modalities for orbital imaging. Ultrasound-guided, fine-needle aspiration of a well-circumscribed orbital mass may provide cellular material for diagnostic evaluation. Exenteration is typically recommended as palliative therapy for primary orbital neoplasms, particularly in cases where the associated eye is blind or painful owing to the effects of exposure. Intraoperative cryotherapy or postoperative radiation treatment is recommended as adjunctive therapy in cases where malignant orbital tumors are suspected or confirmed with histopathology. Orbitotomy 6s,69 for salvage of a visual eye may be considered when diagnostic imaging and cytologic analysis of 82
Primary ocular LSA has not been documented in humans or animals, but ocular signs may be the initial presentation of this multisystemic disease. 70-72The uveal tract is a common site for metastasis of neoplastic lymphocytes, probably via hematogenous spread. 71~73 Ophthalmic disease was present in 37% of dogs with lymphoma in one prospective study of 94 animals, making ocular disease the most consistent presenting sign of multicentric lymphoma after lymphadenopathy.74 Ophthalmic disease in dogs is most common with lymphoblastic lymphoma and in those with LSA-related hematologic abnormalities. Anterior uveitis and intraocular hemorrhage are the most common manifestations (Table 5); however, infiltration of all ocular structures with neoplastic cells can occur 75 (Fig 11).
TABLE 3. Orbital Tumors in Cats and Dogs
Primary Multilobular tumor of bone Optic nerve meningloma Optic nerve glioma Hemangiosarcoma Mast cell tumor Chondrosarcoma Neurofibrosarcoma Rhabdosarcoma Osteosarcoma Adenocarcinoma Lacrimal gland Zygomatic salivary gland Myxoma/myxosarcoma
Secondary by Extension Adenocarcinoma Nasal cavity Gland of nictitating membrane Squamous cell carcinoma: most common tumor in cats Eyelids Oral cavity Nasal cavity Melanoma Conjunctiva Intraocular (uveal) Eyelid
Secondary by Metastasis Multicentric lymphosarcoma Adenocarcinoma Mammary gland Uterus Kidney Thyroid gland Apocrine sweat gland Melanoma Transitional cell carcinoma Fibrosarcoma Hemangiosarcoma Bronchogenic carcinoma WILLIS AND WILKIE
".,
,
Fig 10. (A) Exophthalmos in an aged cat. Protrusion of the third eyelid, a dilated pupil, and blindness were noted clinically in the left eye. Orbital exenteration revealed an orbital fibrosarcoma. (B) Exophthalmos in a young basset hound. The visual right eye is pushed dorsally by a multilobular tumor of bone involving the orbital bones.
Multiple Myeloma Hyphema, corneal edema, aqueous flare, retinal venous dilation with sacculations or tortuosity, retinal hemorrhages, retinal detachment, and secondary glaucoma have been reported in the eyes of animals with multiple myeloma, z6-Fs In some cases, ophthalmic manifestations are the presenting complaint in affected animals, z9 Ocular signs occur secondary to hyperviscosity, which leads to increased vascular volume and hemorrhagic tendencies, z7 An extramedullary orbital plasmacytoma was identified in a cat with monoclonal gammopathy and acute exophthalmos. The exophthalmos was presumed to be associated with acute orbital bleeding from the tumor that was impinged upon by the mandibular ramus when the cat's owner attempted to medicate the cat orally, so Metastatic N e o p l a s i a Intraocular metastasis from primary tumors at distant sites is uncommon, but varieties have been reported• Animals are often presented for the secondary manifestations of intraocular invasion of neoplastic cells, such as uveitis, hyphema, or secondary glaucoma. Adenocarcinomas have been reported to metastasize to the canine and feline eye. Primary tumors include the adenocarcinomas of the lung, sl m a m m a r y tissue, s2-84 thyroid
TABLE 4. Clinical Signs of Orbital Neoplasia in Dogs and Cats Clinical Sign
Comments
Protrusion of nictitating membrane Resistance to retropulsion of globe Slowly progressive exophthalmos Globe deviation Blindness
Occasional hyperemia/chemosis of conjunctiva
Pupil dilation
OCULAR ONCOLOGY
gland, 82 kidney, s5 pancreas, 82 and uterus. 82 An ischemic chorioretinopathy has recently been described in four cats with angioinvasive bronchogenic carcinoma. 86 Extension of an aural SCC 87 to the orbit and eye was reported in a cat. Hemangiosarcoma, s8 transitional cell carcinoma, s9 pheochromocytoma, 9° seminoma, 9~ fibrosarcoma, 92,93 and melanoma s5,94 have all been reported to metastasize to the eye from distant primary sites. Canine transmissible venereal tumor (TVT) is a disease of low frequency in developed countries, but is endemic in regions of the world with large populations of stray dogs. 95 On rare occasions, TVT, typically located on the external genitalia of both sexes, has metastasized to the eye and associated structures. 95,96 A complete physical examination aimed at identifying a source of primary disease is the key feature of an evaluation of an animal with any inflammatory or hemorrhagic intraocular condition not readily explained by a known trauma or preexisting primary ocular disease. Other diagnostic tests are pursued based on the results of additional clinical signs of disease• In addition, particular attention to the nasal and oral cavities is
TABLE 5. Ophthalmic Manifestations of Systemic Neoplasia Tumor
Ophthalmic Signs
Lymphosarcoma
Anterior uveitis Intraocular hemorrhage hyphema retinal hemorrhage Posterior uveitis PanuveitJs Retinal detachment Uveal mass Pupillary dysfunction, anisocoria, dyscoria Infiltrative keratitis Conjunctwal and third eyelid masses Secondary glaucoma (due to chronic uveitis or cellular infiltration of iridocorneal angle Intraocular hemorrhage hyphema retinal hemorrhage Retinal detachment Anterior uveitis Secondary glaucoma
Enophthalmos reported in cat Direction depends on location of tumor Secondary to optic nerve involvement/ compression Secondary to retinal degeneration or detachment Afferent deficit optic nerve involvement/compression Efferent deficit involvement of parasympathetic nerves to iris
Multiple myeloma
8;3
Fig 11. Neoplastic infiltration of multiple ocular structures in a puppy with multicentric lymphoma. Mass lesions are present in the conjunctiva and the third eyelid. The iris is infiltrated with a mass ventrolaterally, creating a dyscoria of the pupil. Exophthalmos is also present in association with orbital involvement.
warranted to rule out orbital metastasis by local extension (Table 3). In cases of systemic neoplasia, appropriate chemotherapy may cause ocular lesions to regress. However, specific topical therapy may be required to manage intraocular inflammation. Metastatic tumors in the eye are typically managed with enucleation if the owner elects palliative therapy. Enucleation of a painful or blind eye that is resistant to medical therapy in an animal for which systemic or metastatic neoplasia is suspected, but not confirmed, may provide the clinician with valuable diagnostic information.
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85