Hereditary benign intraepithelial dyskeratosis (HBID) is an inherited disorder of epithelial maturation of the oral mucosa and bulbar conjunctiva. Autosomal-dominant transmission with high penetrance has been reported (1). HBID affects a population of triracial heritage (African, native American, and Caucasian) located in northeastern North Carolina in Halifax and Washington counties, and therefore known as Haliwa Indians. A family with identical phenotype but no known relationship to Haliwa Indians has also been described (2).

Dilated superficial vessels are associated with elevated keratotic plaques in the nasal and temporal perilimbal regions of the bulbar conjunctiva (Fig. 41-1). Vision may be affected if plaques affect the central cornea. The chronic conjunctival hyperemia is recognized as the “red eye” in the endemic community (3). HBID may be initially mistaken for limbal vernal keratoconjunctivitis. Tearing and photophobia are common. Oral lesions, varying from spongy areas to thick plaques, have been found in all cases. No malignant transformation of ocular or oral lesions has been reported (4).

Pathologic examination reveals the benign nature of the lesion. Acanthosis and hyperkeratosis are seen, as well as a characteristic inclusion of keratin within individual cells (dyskeratosis). No cellular atypia is present. Treatment consists of ocular lubrication for mild irritation. Topical corticosteroids may be helpful for exacerbations of inflammation and irritation. Lesions will recur after excision, but removal of plaques affecting vision is helpful (5).

Squamous papillomas are benign proliferations of conjunctival surface epithelium. Conjunctival papillomas may occur at any age, but are most common between the ages of 20 and 39 years (6). Papilloma accounted for 7% of 302 epibulbar tumors in children under age 15 (7). The predominant growth pattern is exophytic and may be exuberant, involving a large portion of the ocular surface (Fig. 41-2). Limbal papillomas may extend into corneal epithelium (8). Inverted papillomas of the conjunctiva, with downward growth, are rare (9). Pedunculated multiple papillomas are usually of viral origin, whereas sessile papillomatous lesions in elderly patients may represent an intraepithelial neoplasm.

Human papilloma virus (HPV) is an oncogenic double-stranded DNA papovirus implicated in verrucae (skin warts), condylomata acuminata (venereal warts) and mucocutaneous papillomas. Conjunctival inoculation with HPV may occur with delivery through an infected birth canal, through sexual contact, or by autoinoculation (10). Sjo and colleagues (6) identified the DNA of HPV type 6 or 11 in over 80% of
conjunctival papilloma samples tested by polymerase chain reaction (PCR). Eng and colleagues (11) demonstrated HPV 6 or 11 in 58% of conjunctival papillomas.

Standard therapy of papillomas consists of surgical excision, with cautery or cryotherapy of the base (12,13). Despite thorough destruction of the lesions and adjacent epithelium, papillomas may recur. Vaporization of lesions with a carbon dioxide laser may be beneficial in the treatment of recurrent papillomas (14). Mitomycin-C 0.3 mg/mL on a cellulose sponge applied to the epithelial defect for 3 minutes after excision has proven helpful in preventing recurrence (15). Topical mitomycin C 0.02% applied four times daily for 2 weeks, beginning 1 week after excision, has also been employed successfully in the management of recurrent papillomas (16). Caution should be employed in treating an area of conjunctival excision with topical mitomycin C, because of reports of scleral thinning and perforation in bare sclera pterygium excision treated with mitomycin C (17).

Intramuscular interferon-alfa-N1 given daily for 1 month suppressed the recurrence of papillomas after excision, but was not felt to be curative (18). Topical interferon-alfa-2b 1 million units/mL four times daily has resulted in resolution of papillomas by 3 months without surgical excision (19). Four months of oral therapy with liquid cimetidine 30/mg/kg was successful in resolving recalcitrant, diffuse conjunctival papillomatosis in a child (20). Cimetidine is a histamine-2 receptor antagonist, which also has immunomodulation properties, such as inhibition of suppressor T-cell function.

Microscopically, papillomas consist of multiple branching fronds, emanating from a pedunculated base. Acanthotic nonkeratinizing epithelium surrounds a vascularized core of connective tissue, often with light inflammation. Koilocytes, viral inclusions within the epithelium, are a variable finding within papillomas.

Epithelial neoplasia of the ocular surface is considered a disease complex, comprising a spectrum of changes originating within the epithelial layers. Previously used terms for this condition include Bowen’s disease and ocular surface squamous neoplasia. Pizzarello and Jakobiec suggested the currently used term, conjunctival intraepithelial neoplasia (CIN), similar to cervical intraepithelial neoplasia used in gynecologic pathology (21). Conjunctival-corneal intraepithelial dysplasia (CCIN) is appropriate if the cornea is also involved (22). The earliest change is dysplasia, confined by the underlying epithelial basement membrane. Increasing degrees of dysplasia occur if the process is not arrested, culminating in transgression of the basement membrane with invasion of the underlying space and structures. This invasion of subjacent tissue is the hallmark of squamous cell carcinoma (Fig. 41-3). Histologic examination is required for definitive diagnosis.