Conjunctival Melanocytic Proliferations

Clinical Findings

Complexion-associated melanosis, as implied in the name, tends to affect individuals with dark skin. Clinically it manifests as fine pigmentation that is usually bilateral ( Fig. 22.1 ). It can be asymmetric and is found most frequently in the limbal area. The pigment does not have any intrinsic or feeder vessels nor does it extend on to the corneal epithelium or have significant thickness.

Histopathologic Features

This type of melanosis is rarely biopsied, unless there is clinical evidence of atypical progression and there is concern about a possible melanocytic neoplasm. The most important issue is assessing melanocyte density. The density of melanocytes in complexion-associated melanosis is within normal limits. There is no associated melanocytic neoplasm. The clinically visible pigment is related to an increase in the deposition of melanin pigment in epithelial cells and/or stromal melanophages.

Prognosis and Treatment

Complexion-associated melanosis is not a precursor condition for melanoma. It is benign and does not require treatment. If rapid asymmetric irregular growth occurs, then a biopsy should be performed to distinguish it from primary acquired melanosis (PAM) and most importantly to exclude melanoma.

Clinical Findings

Conjunctival melanocytic nevi usually appear as brown elevated lesions on the conjunctiva ( Figs. 22.2 and 22.3 ). Some lesions may be present at birth, but most are noted during the first two decades of life. They may grow slowly during adolescence but are typically stationary during adulthood. Changes in size and appearance may occur during pregnancy, in response to ultraviolet (UV) exposure, or for other reasons. Usually a conjunctival melanocytic nevus presents as a solitary lesion. It is very rare for multiple nevi to be present on the same eye.

Most conjunctival melanocytic nevi are relatively small, with a mean size of 4 mm. They are most often found on the bulbar conjunctiva, but they may also occur on the limbus or the caruncle. It is rare for nevi to involve the fornices or palpebral conjunctiva. Pigmented lesions located at those sites should prompt suspicion for melanoma and be biopsied if they display atypical clinical findings (e.g., irregular borders, variation in color, change in size). Conjunctival melanocytic nevi tend to have an intrinsic vasculature, are commonly associated with cysts, which can be pigmented or clear, and may have nondilated feeder vessels ( Fig. 22.4 ). They do not extend over the limbus onto the cornea and are freely mobile with the conjunctiva.

With regard to color, most conjunctival melanocytic nevi are brown, but the degree of pigmentation varies from dark to light brown to amelanotic. In contrast to cutaneous blue nevi, conjunctival blue nevi are dark brown rather than blue because the Tyndall affect does not apply to the conjunctival mucosa. Most blue nevi are discrete and localized ( Fig. 22.5 ). A distinct variant is conjunctival (diffuse) melanocytosis is the nevus of Ota ( nevus fuscoceruleus ophthalmomaxillaris ) ( Fig. 22.6 ). An ordinary or cellular blue nevus may develop in a background of nevus of Ota.

Histopathologic Features

Conjunctival melanocytic nevi may be confined to the conjunctival mucosa (“junctional” nevus), involve both the mucosa and submucosa (“compound” nevus), or are located only in the stroma (subepithelial nevus). Pure junctional lesions ( Fig. 22.7 ) are rare (≤5% of conjunctival nevi). Most (nearly 80% of) melanocytic nevi of the conjunctiva are compound ( Fig. 22.8 ), and 10% to 15% are subepithelial ( Fig. 22.9 ). A typical feature of conjunctival melanocytic nevi is the presence of epithelium with goblet cells forming invaginations into the stroma and/or small cysts ( Fig. 22.10 ). Such epithelial-lined cysts are found in approximately half of conjunctival melanocytic nevi. The cytology of the melanocytes within a nevus may vary from large epithelioid, to small epithelioid and/or fusiform. Fusiform melanocytes may display “neurotized” (schwannian) features. A lesion may be uniform in its cytology (e.g., predominantly small epithelioid), but there is often a mixture of cell types. Some melanocytic nevi are inflamed and hypervascular, simulating clinically and at low power microscopically an inflammatory process or angioma.

Analogous to cutaneous melanocytic nevi, histologic variants of conjunctival nevi have been reported, including blue nevi (common and cellular blue nevi) ( Fig. 22.11 ), Spitz nevi, and balloon cell nevi, as well as combinations in phenotypes (so-called combined nevi), such as ordinary and blue nevus, and ordinary nevi with a second population of large pigmented epithelioid melanocytes ( Fig. 22.12 ), or melanocytes with spitzoid, spindle cell, clear ( Fig. 22.13 ), balloon, or granular cell features. Melanocytic nevi of the conjunctiva usually display good evidence of maturation and lack mitotic figures. A variant of conjunctival melanocytic nevus, which tends to be seen in young children, that is associated with a greater extent of architectural disorder than usually seen has been referred to as “atypical nevus of the conjunctiva” or “juvenile conjunctival nevus.” Architecturally, these lesions typically display a broad shoulder and contain unusually large and confluent junctional nests, often with discohesion of cells within nests. The submucosal component may be densely cellular. Cytologically, one may find nuclear pleomorphism with limited maturation and rare mitotic figures.

Approximately half of the common types of conjunctival melanocytic nevi carry the BRAFV600E mutation ( Fig. 22.14 ). Another common driver mutation found in conjunctival melanocytic nevi is NRASQ61R ( Fig. 22.15 ). Conjunctival blue nevi tend to carry GNAQ or GNA11 mutations. To date, no cytogenetic aberrations have been reported in conjunctival melanocytic nevi.

Differential Diagnosis

Although clinically for amelanotic nevi the differential diagnosis is broader, the main histopathologic distinction of nevi is from conjunctival melanoma. Features favoring a melanocytic nevus ( Box 22.1 ) include sharp circumscription and lateral demarcation, evidence of maturation, lack of mitotic figures, or nuclear pleomorphism. Caution is needed not to overemphasize one single diagnostic parameter. Irregular junctional growth with confluent nests, variation in size and shape of nests, and/or suprabasilar distribution of melanocytes can be seen in a conjunctival melanocytic nevus and does not necessarily imply melanoma. Correlation with clinical findings (e.g., age of onset, anatomic location, clinical change) is important to arrive at the correct diagnosis. For diagnostically problematic cases (e.g., “atypical” conjunctival nevi), ancillary cytogenetic studies may be helpful. They commonly reveal copy number changes in melanoma but are usually negative in melanocytic nevi.