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Basics ⬇

Outline

BASICS

Definition!!navigator!!

A malignant epithelial tumor of the eyelids, nictitans, conjunctiva, cornea, or limbus that is locally invasive but typically slow to metastasize.

Pathophysiology!!navigator!!

Etiopathogenesis is multifactorial. Predisposing factors include solar radiation, reduced periocular pigmentation, viral agents, advanced age, and genetic and immunologic factors. UV radiation targets the tumor suppressor gene p53, which is altered in equine SCC. Malignant lesions are usually preceded by actinic keratosis, solar elastosis, and epithelial dysplasia.

Systems Affected!!navigator!!

  • Ophthalmic—eyelids, nictitans, conjunctiva, cornea, limbus
  • Other systems or tissues may be affected by local extension or by metastasis. Any squamous epithelial cell in the body may undergo malignant transformation; however, those exposed to higher levels of UV radiation or those with minimal pigment are most susceptible

Genetics!!navigator!!

  • No proven genetic basis, but apparent breed predispositions suggest heritability, and affected horses have mutant forms of the tumor suppressor gene
  • Reduced periocular pigmentation inherited in certain breeds may predispose to ocular SCC

Incidence/Prevalence!!navigator!!

  • Most common equine ocular/adnexal tumor
  • Nictitating membrane and medial canthus are the most common sites, followed by limbus and eyelid

Geographic Distribution!!navigator!!

Increased prevalence with increase in longitude, altitude, or mean annual solar radiation.

Signalment!!navigator!!

Breed Predilections

  • An increased prevalence for SCC has been reported in Belgians, Clydesdales, other draft horses, Haflingers, Appaloosas, and Paints, with the lowest prevalence found in Arabians, Thoroughbreds, and Quarter Horses.
  • White, chestnut, and palomino animals affected more frequently than those with bay, brown, and black hair coats

Mean Age and Range

Prevalence increases with age. Mean age at presentation approximately 10 years.

Predominant Sex

No proven sex predilection.

Signs!!navigator!!

Historical Findings

  • Epiphora or ocular discharge, squinting, redness or cloudiness of the cornea, or redness or ulceration of the eyelid margins or nictitans
  • In advanced cases, raised, ulcerated, or proliferative masses, sometimes resembling granulation tissue, may be noted

Physical Examination Findings

  • Nonspecific findings include serous to mucopurulent ocular discharge, blepharospasm, nictitans prolapse, and conjunctival hyperemia
  • Closer inspection may reveal red to white plaque-like, proliferative, or erosive lesions of the eyelids, nictitans, conjunctiva, or limbus. On the cornea, SCC may be associated with vascularization, cellular infiltration, edema, and fibrosis. Corneal SCC is typically limited to the superficial cornea, though chronic SCC may invade intraocular structures. Chronic SCC may invade the deep tissues of the eyelids and orbit. Thorough palpation, followed by diagnostic imaging (radiography, CT, or MRI) is essential to evaluate the extent of the lesion

Causes!!navigator!!

Unknown

Risk Factors!!navigator!!

  • UV radiation
  • Lack of periocular pigmentation
  • Possible genetic risk factors

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

  • Diagnosis is made on the basis of biopsy results; however, a characteristic clinical appearance is helpful in differentiating SCC from other periocular diseases
  • Differentials include other tumors such as papilloma, sarcoid, fibrosarcoma, lymphoma, and liposarcoma; parasites such as Habronema, Onchocerca, and Thelazia; and inflammatory lesions such as abscesses, granulation tissue, eosinophilic keratoconjunctivitis, and foreign body reactions

CBC/Biochemistry/Urinalysis!!navigator!!

Results usually normal.

Imaging!!navigator!!

  • Skull radiographs may be required if orbital or other bony involvement is suspected
  • Thoracic radiographs are indicated if metastasis is suspected
  • Orbital ultrasonography and CT may be helpful in determining extent of orbital invasion

Other Diagnostic Procedures!!navigator!!

  • Cytologic evaluation of cells obtained by scraping followed by Giemsa or Wright's staining may reveal abnormal epithelial cells suggestive of SCC. Histopathologic examination of a biopsy specimen of the lesion is confirmatory
  • Histopathologic examination of biopsy specimens from regional lymph nodes may indicate presence of metastatic disease

Pathologic Findings!!navigator!!

  • Gross appearance varies from erosive to proliferative. The outer surface may demonstrate inflammation secondary to trauma or bacterial infection, and the mass may be covered by purulent exudate
  • Histologically, the tumor consists of nests or cords of epithelial cells with varying degrees of dermal infiltration. Mitotic figures are common, and intercellular bridges may be present. Well-differentiated tumors form keratin “pearls” consisting of rings with central areas of keratinization. Poorly differentiated tumors usually lack keratin pearls but may exhibit dyskeratosis

Treatment ⬆ ⬇

Outline

TREATMENT

Inpatient Versus Outpatient!!navigator!!

  • Very small, superficial lesions of the eyelids and nictitans may be removed standing with sedation and local anesthesia. Larger, more invasive lesions of the eyelids or nictitans, or lesions involving the conjunctiva or cornea, require hospitalization for surgery
  • Alternatively, eyelid lesions may be treated with local anesthesia using intralesional chemotherapy or PDT

Activity!!navigator!!

Restrict during immediate postoperative period. The eye should be protected from self-trauma with a soft- or hard-cup hood.

Client Education!!navigator!!

  • If intralesional chemotherapy is used, the client should wear gloves when handling the periocular region for several days post injection
  • The client should be aware of signs of recurrence, metastasis, or the development of new lesions
  • The client should also be aware of the possible role of UV radiation in order to take appropriate steps to minimize exposure to solar radiation

Surgical Considerations!!navigator!!

  • Tumors may be removed by surgical excision alone if adequate margins can be obtained. However, adjunctive therapy is often necessary, especially with large or invasive tumors. Adjunctive therapies include PDT, cryotherapy, irradiation, radiofrequency hyperthermia, CO2 laser ablation, and intralesional chemotherapy. Reconstructive eyelid surgery may be required when eyelid margins are lost following tumor excision, and conjunctival or amniotic membrane grafts may be required following keratectomy
  • Cryosurgery with liquid nitrogen or nitrous oxide induces cryonecrosis of malignant cells (–20°C to –40°C, double freeze–thaw technique). Beta-irradiation (strontium-90) is most beneficial in SCC of the cornea and limbus following superficial keratectomy, with reported success rates approaching 80%. Brachytherapy may be used following surgical debulking of invasive eyelid tumors. Small, superficial tumors may be treated with radiofrequency hyperthermia (41–50°C) following surgical excision. Excision of corneal limbal SCC followed by CO2 laser ablation has also been advocated. Debulking of eyelid tumors followed by PDT is showing great promise in early studies

Medications ⬆ ⬇

MEDICATIONS

Drug(s) and Fluids

Topical and Intralesional Immunotherapy/Chemotherapy

  • Immunotherapy with bacillus Calmette–Guérin (BCG) cell wall extract has been used successfully for some periocular SCCs in horses
  • Chemotherapy with intralesional, slow-release cisplatin or carboplatin has also been used with variable success. At least 4 sessions (sometimes more until tumor-free biopsy results are obtained) at 1–2 week intervals using 1 mg/cm3 are necessary. Tumors up to 20 cm3 may be treated using 3.3 mg/mL cisplatin or carboplatin in purified medical-grade sesame oil. If this therapeutic modality is chosen, the owner must be committed to the entire course of therapy because if the injections are prematurely discontinued, the tumor that recurs often will be resistant to treatment thereafter
  • PDT consists of intralesional injection of the affected site with a photoactive dye that causes tumor cell death when the appropriate wavelength of light is applied to the wound bed
  • Piroxicam (150 mg PO daily) can be beneficial in some ocular SCCs. The drug is begun once a day and then reduced to every other day
  • Topical 5-fluorouracil (1% TID) or mitomycin C (0.02% QID) may be effective for corneal SCC in situ

Supportive Therapy

Topical and systemic broad-spectrum antibiotics may be required to prevent infection following surgical and adjunctive therapy of ocular/adnexal SCC. Topical atropine (1%) is used following keratectomy of corneal SCC to treat reflex anterior uveitis. Systemic NSAIDs are indicated following surgical excision or intralesional chemotherapy.

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

Patients should be observed closely for recurrence of lesions, new lesions, and signs of metastasis. Tumor recurrence has been reported months to years post treatment.

Prevention/Avoidance!!navigator!!

Reduction of solar radiation exposure, through either avoidance of light (stalling during daytime, nighttime turnout) or use of protective headgear (fly masks), may reduce the incidence of recurrence or new tumor growth. Early recognition and intervention are critical to a successful outcome.

Possible Complications!!navigator!!

  • Tumor progression may lead to orbital involvement with subsequent exophthalmos, necessitating orbital exenteration
  • Local invasion usually occurs in the orbit, guttural pouch, or nasal cavity
  • Limbal SCC may invade intraocular structures, necessitating enucleation
  • Chronic ulceration or tissue necrosis may lead to secondary infection and possible septicemia
  • Metastasis occurs in 10–15% of horses with SCC, with regional lymph nodes, parotid salivary glands, and thorax being the most frequently affected sites

Expected Course and Prognosis!!navigator!!

  • Prognosis is better if treatment is started early in the course of disease and owners are committed to long-term follow-up therapy and monitoring
  • Factors affecting prognosis include tumor location, degree of invasiveness, presence or absence of metastasis, and the number of tumors present at the time of diagnosis
  • Recurrence rates following therapy range from 25% to 42%
  • Third eyelid tumors and eyelid tumors tend to spread and metastasize more frequently than does limbal SCC

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Associated Conditions!!navigator!!

Precancerous changes include actinic keratosis, solar elastosis, and epithelial dysplasia.

Abbreviations!!navigator!!

  • CT = computed tomography
  • MRI = magnetic resonance imaging
  • NSAID = nonsteroidal anti-inflammatory drug
  • PDT = photodynamic therapy
  • SCC = squamous cell carcinoma
  • UV = ultraviolet

Suggested Reading ⬆ ⬇

Brooks DE. Ophthalmology for the Equine Practitioner, 2e. Jackson, WY: Teton NewMedia, 2008.

Brooks DE, Matthews AG. Equine ophthalmology. In: Gelatt KN, ed. Veterinary Ophthalmology, 4e. Ames, IA: Blackwell, 2007:1165–1274.

Gilger BC, ed. Equine Ophthalmology, 3e. Ames, IA: Wiley Blackwell, 2017.

Author(s) ⬆

Author: Caryn E. Plummer

Consulting Editor: Caryn E. Plummer