Melanocytic Neoplasms of the Conjunctiva

Introduction

Conjunctival melanocytic lesions form the majority (approximately 53%) of all conjunctival lesions. ^, They originate from several melanin-containing cells in the conjunctiva and range from benign to potentially fatal malignant neoplasms.

Melanocytes are specialized cells capable of producing the complex protein melanin and are a normal constituent of conjunctival epithelium. In their normal location at the base of the epithelium, melanocytes do not contain pigment in white individuals and are difficult to identify by light microscopy without the use of special immune-histochemical stains, such as S-100, HMB-45, and Melan-A. Melanin production is stimulated by several events, including exposure to ultraviolet light. Melanin is exported from the melanocyte via delicate dendritic (branching) cellular processes to neighboring epithelial cells. The additional melanin produced plays a role in protecting epithelial cells from the harmful effects of ultraviolet light. Inflammation, trauma, and various hormones may also stimulate melanin production.

Melanocytic nevus cells do not have dendritic processes and retain rather than distribute melanin. Certain subgroups of nevus cells are found at the junction of the conjunctival epithelium and the conjunctival stroma. Over time, nevus cells tend to lose pigment and move deeper into the conjunctival stroma. Other types of nevus cells are stationary in location and remain at deeper sites, even to the level of episcleral tissue. Clinical clues to the tissue location of the nevus cells are indicated by the apparent color of the melanin: superficial golden brown to deep blue-gray.

Not all cells containing melanin are melanocytes. Damaged or senescent melanocytes may discharge melanin into the surrounding matrix to be phagocytized by macrophages (melanophages). Increasing pigmentation of a melanocytic lesion may be due to melanin in macrophages rather than melanin in neoplastic cells.

Both melanocytes and nevus cells have the potential to undergo malignant transformation to malignant melanoma. Melanophages have no potential for malignant transformation. The various melanocytic lesions develop either due to increased melanin deposition or due to proliferation of the melanin-containing cells.

Clinical and Histopathologic Features of Conjunctival Melanocytic Lesions

Conjunctival Nevus

The melanocytic nevi of the conjunctiva are classified by tissue location relative to the surface epithelium, similar to types of nevi of the skin: junctional (at the epithelial–stromal junction), compound (junctional and stromal components), subepithelial (limited to the stroma), blue (oval to round melanocytes in subepithelium), and cellular blue (spindle-shaped melanocytes in the subepithelial tissue).

Like cutaneous nevi, conjunctival nevi evolve with age. Pure intraepithelial (junctional) nevi are present most commonly in younger individuals. ^, Over time, nevus cells drop from the epithelium to the stroma. Most conjunctival nevi are compound or subepithelial. Blue and cellular blue nevi are seldom encountered in the conjunctiva. In patients with the nevus of Ota, the discrete bluish episcleral spots may be considered special examples of blue nevi. When there is a combination of an intraepithelial, compound, or subepithelial nevus with a blue or cellular blue nevus, the lesion is designated a combined nevus.

Subepithelial and compound nevi are similar in their clinical and histologic characteristics. Compound nevi have residual junctional proliferation of nevus cells. Inclusions of conjunctival epithelium in the form of cysts are usually observed with conjunctival nevi ( Figs. 53.1 and 53.2 ), which may represent an anomalous development of the conjunctival epithelium. Nevi are typically slightly elevated from the conjunctival surface with well-defined margins (see Fig. 53.1 ). The degree of pigmentation is variable in conjunctival nevi. Some nevi are totally amelanotic, and, when the lesion is small, the epithelial inclusions may predominate.

In young individuals, significant cytologic pleomorphism may be present in conjunctival nevi, and large spindle- or epithelioid-shaped melanocytes characteristic of “Spitz nevi” may be encountered.

Conjunctival nevi may change or become more noticeable during puberty as melanocytes may proliferate or increase pigment production. Conjunctival epithelial cells within inclusions may proliferate and secrete extracellular material, enlarging the size of the cysts. Inflammatory cell infiltration further increases the size, elevation, and vascularity of the nevus.

Malignant melanoma may arise from any type of nevus, including from a conjunctival blue nevus.