periods (1 to 2 weeks), with a drug holiday of 2 to 4 weeks between treatments. Application of topical corticosteroids may help with the surface toxicity. Placement of punctal plugs reduces the chance of systemic absorption and helps prevent punctal stenosis. MMC is effective in the treatment of both squamous cell carcinoma and atypical melanocytic lesions of the conjunctiva; it is relatively inexpensive; and it works more quickly than topical interferon-α2b. However, the potential toxicity of MMC, both during and after application, is significant. 5-Fluorouracil is used less frequently but may be considered if the other agents are unavailable, ineffective, or not tolerated.
Once a tumor has been managed, long-term, regular follow-up is essential, because malignant conjunctival tumors can recur. Complete examination of the ocular surface and palpation of regional lymph nodes should be performed at each visit. Patients with malignant ocular surface tumors should be referred to a dermatologist for a complete skin evaluation.
The remainder of this chapter will focus on the clinical characteristics of various benign and malignant tumors of the ocular surface.
Jakobiec FA, Bhat P, Colby KA. Immunohistochemical studies of conjunctival nevi and melanomas. Arch Ophthalmol. 2010;128(2):174–183.
Koreishi AF, Karp CL. Ocular surface neoplasia. Focal Points: Clinical Modules for Ophthalmologists. San Francisco: American Academy of Ophthalmology; 2007, module 1.
Nordlund ML, Brilakis HS, Holland EJ. Surgical techniques for ocular surface reconstruction. Focal Points: Clinical Modules for Ophthalmologists. San Francisco: American Academy of Ophthalmology; 2006, module 12.
Shields JA, Shields CL, De Potter P. Surgical management of conjunctival tumors. The 1994 Lynn B. McMahan Lecture. Arch Ophthalmol. 1997;115(6):808–815.
Sturges A, Butt AL, Lai JE, et al. Topical interferon or surgical excision for the management of primary ocular surface squamous neoplasia. Ophthalmology. 2008;115(8):1297–1302.
Tumors of Epithelial Origin
Table 8-1 lists the epithelial tumors of the conjunctiva and cornea.
Warner MA, Mehta MN, Jakobiec FA. Squamous neoplasms of the conjunctiva. In: Krachmer JH, Mannis MJ, Holland EJ, eds. Cornea. 3rd ed. Vol 1. Philadelphia: Elsevier/Mosby; 2011:461–476.
Table 8-1
Benign Epithelial Tumors
Conjunctival papilloma
The 2 forms of conjunctival papilloma, sessile and pedunculated, have etiologic, histologic, and clinical differences.
PATHOGENESIS Human papillomavirus (HPV), subtype 6 (in children) or 16 (in adults), initiates a neoplastic growth of epithelial cells with vascular proliferation that gives rise to a pedunculated papilloma of the conjunctiva. Though also usually benign, a sessile conjunctival lesion may represent a dysplastic or carcinomatous lesion, especially when caused by HPV-16 or HPV-18.
CLINICAL FINDINGS A pedunculated conjunctival papilloma is a fleshy, exophytic growth with a
fibrovascular core (Fig 8-1A). It often arises in the inferior fornix but can also present on the tarsal or bulbar conjunctiva or along the semilunar fold. The lesion emanates from a stalk and has a multilobulated appearance with smooth, clear epithelium and numerous underlying, small corkscrew blood vessels. Multiple lesions sometimes occur, and the lesion may be extensive in patients with compromised immunity.
Figure 8-1 Conjunctival squamous papilloma. A, Pedunculated. B, Sessile. (Reproduced with permission from Krachmer JH, Mannis
MJ, Holland EJ, eds. Cornea. 3rd ed. Vol 1. Philadelphia: Elsevier/Mosby; 2011:463.)
A sessile papilloma is more typically found at the limbus and has a flat base (Fig 8-1B). With its glistening surface and numerous red dots, this form of papilloma resembles a strawberry. The lesion may spread onto the cornea. Signs of dysplasia include keratinization (leukoplakia), symblepharon formation, inflammation, and invasion. A very rare variant is an inverted papilloma.
MANAGEMENT Many conjunctival papillomas regress spontaneously. A pedunculated papilloma that is small, cosmetically acceptable, and nonirritating may be observed. Spontaneous resolution may take months to years. An incomplete excision, however, can stimulate growth and lead to a worse cosmetic outcome. Cryotherapy alone, excision with cryotherapy to the base, or excision with adjunctive application of interferon-α2b is sometimes curative, but recurrences are frequent. Surgical manipulation should be minimized to reduce the risk of virus dissemination to uninvolved healthy conjunctiva. Oral cimetidine may be a systemic adjunct acting as an immunomodulator.
A sessile limbal papilloma must be observed closely or excised. If the lesion enlarges or shows clinical features suggesting dysplastic or carcinomatous growth, then excisional biopsy with adjunctive cryotherapy is indicated.
Preinvasive Epithelial Lesions
Conjunctival intraepithelial neoplasia
Conjunctival intraepithelial neoplasia (CIN), or dysplasia, is analogous to actinic keratosis of the eyelid skin. In CIN, the dysplastic process does not invade the underlying basement membrane and is referred to as mild (CIN I), moderate (CIN II), or severe (CIN III), depending on the extent of involvement of the epithelium with atypical cells. Related terms include squamous dysplasia, if atypical cells involve only part of the epithelium, and carcinoma in situ, when cellular atypia involves the entire thickness of the epithelial layer. See also BCSC Section 4, Ophthalmic Pathology and Intraocular Tumors.
PATHOGENESIS HPV infection, sunlight exposure, and host factors play a role in the development of CIN. The lesion most commonly develops on the interpalpebral bulbar conjunctiva, at or near the limbus, in older male smokers with light complexions who may have been exposed to petroleum products or to the sun over long periods. Rapid growth may occur when the lesion is present in a person with AIDS. Systemic immunosuppression appears to potentiate squamous neoplasia. In a young adult, CIN should instigate a serologic test for human immunodeficiency virus (HIV) infection.
Shields CL, Ramasubramanian A, Mellen PL, Shields JA. Conjunctival squamous cell carcinoma arising in immunosuppressed patients (organ transplant, human immunodeficiency virus infection). Ophthalmology. 2011;118(11):2133–2137.
CLINICAL FINDINGS There are 3 principal clinical variants of CIN (Fig 8-2):
1.papilliform, in which a sessile papilloma harbors dysplastic cells
2.gelatinous, as a result of acanthosis and dysplasia
3.leukoplakic, caused by hyperkeratosis, parakeratosis, and dyskeratosis
Figure 8-2 Conjunctival intraepithelial neoplasia: A, Papilliform. B, Gelatinous. C, Leukoplakic. (Part A courtesy of James Chodosh,
MD; parts B and C courtesy of James J. Reidy, MD.)
Mild inflammation and various degrees of abnormal vascularization may accompany CIN lesions, but large feeder blood vessels indicate a higher probability of invasion beneath the epithelial basement membrane. CIN lesions are slow-growing tumors nearly always centered at the limbus but with the potential to spread to other areas of the ocular surface, including the cornea.
MANAGEMENT See the section Management of Atypical Epithelial Tumors.
Corneal intraepithelial neoplasia
The cornea adjacent to intraepithelial neoplasia of the conjunctiva can also be affected. Sometimes, the conjunctival or limbal component is not clinically apparent, and only a sheet or individual islands of well-demarcated, geographic, epithelial granularity on the cornea are seen.
PATHOGENESIS Corneal intraepithelial neoplasia is associated with the same risk factors as CIN and presumably shares the same pathogenesis.
CLINICAL FINDINGS A granular, translucent, gray epithelial sheet broadly based at the limbus extends onto the cornea. Occasionally, free islands of punctate granular epithelium are present on the cornea. The edges of corneal lesions have characteristic fimbriated margins and pseudopodia-like extensions (Fig 8-3). Rose bengal and lissamine green staining help define the edges of the lesion. Corneal