Nevus is the most common melanocytic conjunctival tumor (1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34). In the authors’ clinical series of 1,643 conjunctival tumors, there were 454 nevi, accounting for 52% of conjunctival melanocytic lesions and for 28% of the 1,643 lesions (3).

There is controversy as to whether conjunctival nevi are congenital or acquired (1). It generally becomes clinically apparent in the first or second decade of life (1,2,3,4,10). The nevus begins as a small nest of melanocytes in the basal layer of the epithelium, at which stage it is called a “junctional” nevus. In the second to third decade of life, the cells gradually migrate into the underlying stroma to form a “compound” nevus. At this stage, characteristic pseudocysts form in the lesion. By the third to fourth decade, the lesion has migrated to reside entirely in the stroma, forming a “subepithelial” nevus (1). It is helpful to consider these three types as stages in the evolution of a nevus, rather than distinct types (1).

Melanocytic nevus of the conjunctiva is generally sporadic with no systemic associations. However, lentigines and nevi are rarely associated with Carney complex and the dysplastic nevus syndrome (DNS) (22). Carney complex is also mentioned in the sections on eyelid and conjunctival myxomas in this atlas. The DNS is an autosomal-dominant entity characterized by numerous dysplastic cutaneous nevi and a high incidence of cutaneous melanoma. There may be an increased incidence of conjunctival nevi (and melanoma) in association with DNS (20).

A recent study of 410 consecutive cases of conjunctival nevi seen by the authors revealed that 89% occurred in Caucasians, 6% in African Americans, and 5% in Asian, Hispanic, or Indian subjects (4). It contained clinically evident pigment in 84% and was clinically amelanotic in 16%. It was located in the bulbar conjunctiva in 72%, caruncle in 15%, semilunar fold in 11%, and fornix, tarsus, and cornea in 1% each. About 90% were located in the interpalpebral area with relative equal distribution nasally and temporally (2). Malignant transformation was estimated to be less than 1%, a finding that is similar to other series (18).

Conjunctival nevus is usually a discrete, mobile lesion on the bulbar conjunctiva, most often in the interpalpebral area. It can range from deeply pigmented to amelanotic. It may become more pigmented with time and this change is misinterpreted by the patient, and sometimes by the physician, as malignant transformation. However, true increase in size sometimes occurs in young children and such enlargement does not necessarily mean malignant transformation into melanoma (34). When it is not pigmented, the presence of multiple, clear cystic spaces seen in the lesion with slit-lamp biomicroscopy help to differentiate nevus from papilloma, lymphoma, and amelanotic melanoma, which generally do not have cysts. Lymphangioma, on the other hand, can have cystlike spaces and resemble a diffuse amelanotic nevus (1,2,12).

Another common clinical variant is what the authors call a speckled nevus. It is less well defined and appears as a patchy area of pigmentation in the conjunctiva. It may closely resemble primary acquired melanosis (PAM), to be discussed shortly, except that it generally occurs in younger individuals and sometimes contains subtle clear cysts, a finding not seen with PAM.

In rare cases, a blue nevus can occur in the conjunctiva. It is often congenital and appears clinically as a blue to black, circumscribed or slightly ill-defined lesion deep to the conjunctival epithelium that differs from the more diffuse scleral or episcleral melanocytosis (1,23). Conjunctival blue nevus can have a diffuse growth pattern and resemble primary acquired melanomas. Such a diffuse blue nevus can rarely undergo malignant transformation into melanoma (21).

Although most nevi develop in the interpalpebral region, they can be located in the extralimbal bulbar conjunctiva, semilunar fold, or caruncle. In rare instances, they can apparently be confined to the palpebral conjunctiva (11) or cornea (24). Such locations should raise suspicion that the lesion is an early melanoma.

In some instances, a conjunctival nevus can assume an irregular or diffuse growth pattern. Such an atypical nevus can occupy a large portion of the conjunctiva and lead to diagnostic confusion with PAM, melanoma and, in the case of amelanotic lesions, with lymphoma or lymphangioma (12). A relatively common occurrence with conjunctival nevus is secondary inflammation, which may simulate primary conjunctivitis or episcleritis (34). However, slit-lamp biomicroscopy often discloses the typical cysts that characterize the nevus.

The histopathological classification of nevi is discussed in the literature (1,2). Although most pathologists accustomed to evaluating ocular tissues can make the diagnosis without difficulty, there are some cases where the lesion has borderline malignant features and even experienced ocular pathologists may have difficulty classifying the lesion as benign or malignant (29). Histopathologically, a conjunctival nevus is composed of a diffuse infiltration or distinct nests of benign melanocytes near the basal layer of the epithelium. Depending on their relationship to the layers of the conjunctiva, they are most often classified as junctional, compound, or deep (1,3). Depending on their cytology and other features, they may be classified as dysplastic nevus, spindle cell nevus, epithelioid cell nevus, balloon cell nevus, or a combination of these variants (1,13,27).

A blue nevus is uncommon in the conjunctiva. It may be identical to the typical congenital or acquired nevus, except that it is more likely to be deep to the conjunctival epithelium, sometimes partially attached to the sclera. It may be dark brown or black and it is less likely to contain cysts.

A variety of other nevi can be occasionally recognized in the conjunctiva histopathologically. There have been examples
of balloon cell nevus, Spitz nevus, epithelioid cell nevus, dysplastic nevus, and melanocytoma in the conjunctiva (8,13).

On occasion, a conjunctival nevus shows features of both a conventional nevus and deeper dendritic cells that characterize a blue nevus. Such a lesion has been called a “combined” nevus. It has recently been stressed that such a nevus may be more common than previously suspected and must be differentiated from a melanoma (16,28).

Currently used immunohistochemical techniques can be used to differentiate melanocytic lesions from nonmelanocytic conditions. However, the popular melanoma-specific antigen (HMB-45) generally shows a positive reaction with both nevus and melanoma and cannot be reliably used to differentiate benign from malignant melanocytic lesions (30).

The best initial management for a small, typical conjunctival nevus is periodic observation with photographs. If growth is documented, local excision of the lesion should be considered. However, relative indications for earlier excision include location in the forniceal or palpebral conjunctiva or cornea, nutrient blood vessels, larger lesion that contains no cysts, positive family history of conjunctival or cutaneous melanoma, distinct onset of the lesion in middle age or later in life, insistence of the patient or parents, and cancerophobia. In addition, any recurrence of a previously excised conjunctival nevus should be removed. Such a recurrence should raise the possibility of malignant transformation. We have sometimes removed a small lesion believed clinically to be a nevus and were surprised to find that it was a melanoma histopathologically.

If a lesion shows suspicious change or growth, it is important that an excisional biopsy be done, using a reported technique, described later in this chapter and illustrated in Chapter 25. As a general rule, incisional biopsy is contraindicated in lesions that can be resected entirely in one procedure. The resection technique that we employ is the same as that used for malignant neoplasms, like squamous cell carcinoma, and other lesions near the limbus. It involves a partial alcohol epitheliectomy, removal of the main tumor by partial lamellar sclerokeratoconjunctivectomy, and double freeze thaw cryotherapy (33).

Most conjunctival nevi are pigmented and located near the limbus in the interpalpebral region. Characteristic clear cysts in the lesion strongly support the diagnosis of compound nevus. Conjunctival nevus can be completely pigmented, partly pigmented, or nonpigmented.

Some conjunctival melanocytic nevi have no apparent pigment on clinical examination. Typical cysts within the lesion on slit-lamp examination, however, should suggest the diagnosis of nevus. All of the lesions shown here had typical cysts, but cysts are not appreciated in every case. Such an amelanotic nevus can become inflamed periodically and be confused with conjunctivitis or episcleritis.

In some instances, a conjunctival nevus is only partly pigmented. The presence of even minimal pigmentation should strongly suggest that the lesion is a melanocytic nevus.

Conjunctival nevi can vary in size, color, and location. Occasionally, a conjunctival nevus may be apparently confined to the cornea. There are some atypical clinical and histopathologic variations of conjunctival nevus. Selected examples include the speckled nevus that might resemble primary acquired melanosis, epithelioid cell nevus, corneal nevus.

Shields JA, Shields CL, Eagle RC Jr, et al. Compound nevus of the cornea simulating a foreign body. Am J Ophthalmol 2000;130:235-236.

Nevi can often be located in the extralimbal bulbar conjunctiva, semilunar fold (plica semilunaris), and the caruncle. Caruncular lesions are discussed and illustrated later.

In some instances, the cysts within a conjunctival nevus can be very prominent and suggest the diagnosis of a primary cystic lesion or a lymphangioma.

A blue nevus may be similar to a typical acquired nevus except that it is located deeper in the stroma and episcleral tissues and it generally lacks cysts. Examples are illustrated.

Conjunctival nevus can assume a number of atypical clinical variations. The amelanotic diffuse variant can be confused clinically with lymphangioma, lymphoma, and other amelanotic lesions.

Rosenfeld SI, Smith ME. Benign cystic nevus of the conjunctiva. Ophthalmology 1983;90:1459-1461.

Congenital episcleral melanocytosis can occur as a solitary lesion but, in a clinical setting, it is more often seen as a component of ocular melanocytosis or oculodermal melanocytosis (nevus of Ota) (1,2,3,4,5,6,7,8). Oculodermal melanocytosis is discussed under the subject of pigmented lesions of the eyelids. Because of the association of the condition with uveal melanoma, it is also discussed in the Atlas of Intraocular Tumors. It is mentioned here because, although not strictly in the conjunctiva, it is included in the differential diagnosis of conjunctival nevus and primary acquired melanosis (PAM) of the conjunctiva.

Clinically, the lesions appear as irregular geographic patches of scleral and episcleral pigmentation that can range from distinct brown to gray in color (1,2,3,4,5,6,7). The pigment can be randomly distributed or it can follow a sector distribution, sometimes corresponding to similar sector pigmentation of the uveal tract. Although we have not observed it in our tumor clinic, reports from other facilities have shown that this condition has a 10% incidence of elevated intraocular pressure or true glaucoma, which can occasionally be congenital or late congenital (6,7). Hyperpigmentation of the nasal and buccal mucosa are often associated with oculodermal melanocytosis.

The diagnosis can usually be made readily with external ocular examination and slit-lamp biomicroscopy. To help differentiate it from a conjunctival lesion, one can move the conjunctiva with a cotton-tipped applicator. The overlying conjunctiva can be moved over the lesion without distorting it, confirming that it is located deep to the conjunctiva. Fundus examination should be done to exclude uveal melanoma.

The scleral and episcleral lesion consists of deeply pigmented dendritic melanocytes with benign cytologic features. In most cases of ocular melanocytosis, the pigmentation involves the sclera and the underlying uveal tract.

No management is necessary for the scleral and episcleral pigmentation of ocular melanocytosis. As mentioned, the patient should be followed for the development of uveal melanoma or secondary glaucoma.

The scleral pigmentation of congenital ocular melanocytosis has typical features and location. It must be differentiated from other diffuse epibulbar pigmentary conditions like primary acquired melanosis and complexion-related pigmentation. Unlike these other conditions, it is attached to the sclera and does not move with manipulation of the conjunctiva.