Melanocytic nevi are benign proliferations of melanocytes that commonly occur on the eyelids. Melanocytic nevi may be visible at birth or shortly after birth (congenital nevi) or become apparent in adolescence or adulthood; congenital nevi tend to be larger than those appearing in later years. Nevi greater than 20 cm in diameter are called giant congenital melanocytic nevi. The risk for development of melanoma in congenital nevi is proportional to the size of the nevus; close follow-up and/or excision of congenital nevi is warranted. Congenital nevi of the eyelid may develop in utero before the separation of the upper and lower eyelids, resulting in matching nevi on these eyelids, termed a kissing nevus (Fig 13-27). Nevi in adults often appear as smooth dome-shaped, sometimes hyperpigmented, lesions on the eyelid margin. Other forms of nevi can occur on the eyelid, including blue nevi, Spitz nevi, and dysplastic nevi, though rarely.
Histologically, most nevi are composed of nevus cells, specialized melanocytes that have a round rather than dendritic shape and tend to cluster together in nests. The cytoplasm of the nevus cell contains a variable amount of melanin. Other characteristics of these cells include growth within and around adnexal structures, vessel walls, and the perineurium and extension into the deep reticular dermis or subcutaneous tissue. When a combination of round and spindle-shaped cells is seen in a lesion, the term combined nevus is used.
Nevi typically begin as macular (flat) lesions and evolve with age. In childhood, histologic examination reveals nests of nevus cells in the epidermis, along the dermal–epidermal junction, termed junctional nevus (Fig 13-28). Clinically, a junctional nevus is indistinguishable from an ephelis (freckle), but histologically, the latter demonstrates pigment in the basal layer of the epidermal epithelial cells. Typically in adolescence, the junctional nests of nevus cells continue to proliferate and migrate into the superficial dermis, and the nevus becomes increasingly elevated clinically. At this stage, the nevus may also increase in pigmentation. When both junctional and intradermal components are present, the histologic classification is compound nevus (Fig 13-29). Finally, sometime in adulthood, the junctional component disappears, leaving nevus cells only within the dermis, and, accordingly, the classification is intradermal or dermal nevus (Fig 13-30).
The cytologic appearance of nevus cells also evolves: the cells in the superficial portion of the nevus are round and have round to ovoid nuclei (type A nevus cells). Within the midportion, the cells are smaller, have less cytoplasm, and resemble lymphocytes (type B nevus cells). In the deepest portion, the nevus cells appear similar to Schwann cells of peripheral nerves with a spindle configuration (type C nevus cells). Recognition of this “maturation” is useful for classifying melanocytic neoplasms as benign. Multinucleated giant nevus cells and interspersed adipose tissue are common in older nevi.
Figure 13-28 Junctional nevus. Nests of nevus cells (pigmented in this case) are apparent at the dermal–epidermal junction.
Figure 13-29 Compound nevus. Nests of nevus cells are present in the dermis (arrows) as well as at the dermal–epidermal junction (arrowheads).
(Courtesy of Nasreen A. Syed, MD.)
Figure 13-30 Intradermal nevus. The nests of nevus cells are confined to the dermis, and there is no junctional component. The superficial extent of the nevus cell nests is indicated with arrowheads.
(Courtesy of Nasreen A. Syed, MD.)
Cutaneous melanoma occurs rarely on the eyelids. It may be associated with a preexisting nevus, develop de novo, or extend from a tumor elsewhere on the face. In a pigmented eyelid lesion, clinical features that suggest malignancy include asymmetry, border irregularity, color variegation, and diameter greater than 6 mm. Melanoma may be heralded by a vertical (perpendicular to the skin surface) growth phase. There are 3 main histologic subtypes of melanoma that occur on the eyelids (Fig 13-31):
Lentigo maligna melanoma, the most common type occurring on the eyelids, typically develops as an irregular pigmented macular lesion on the face in older adults and has a long preinvasive phase. Histologically, atypical melanocytes proliferate along the dermal–epidermal junction as single or small nests of cells in the epidermis, similar to primary acquired melanosis with atypia of the conjunctiva. Superficial invasion of the dermis is also present. Superficial spreading melanoma, the most common type of cutaneous melanoma, demonstrates a radial (intraepidermal) growth pattern that extends beyond the invasive component. Nodular melanoma has a significant vertical growth phase that results in a raised or indurated mass.
Figure 13-31 Schematic illustration of cutaneous melanoma types. A, Lentigo maligna melanoma. Atypical melanocytes (brown cells) proliferate predominantly in the basal layers of the epidermis in a linear or nested pattern, similar to primary acquired melanosis with atypia of the conjunctiva. Note the tendency of the melanocytes to involve the outer sheaths of the hair shafts. The invasive component is seen as brown cells (spindle and epithelioid) in the superficial dermis. B, In superficial spreading melanoma, tumor cell nests are present in all levels of the epidermis, often in a pagetoid fashion, with cells or clusters of cells scattered among epithelial cells. Lentigo maligna and superficial spreading melanomas spread horizontally (radial growth) through the skin, staying close to the dermal–epidermal junction. C, Nodular melanoma has a narrow intraepidermal component and more prominent vertical growth within the dermis; it is therefore more deeply invasive than the other types.
(Modified with permission from Spencer WH, ed. Ophthalmic Pathology: An Atlas and Textbook.Vol 4. Saunders; 1996:2270. Illustration by Christine Gralapp.)
The characteristic histologic features of melanoma include pagetoid intraepidermal spread of atypical melanocytic nests and single cells, nuclear abnormalities, lack of maturation in the deeper portions of the mass, and atypical mitotic figures. A bandlike lymphocytic host response along the base of the mass is more common in melanoma than in benign proliferations. Prognosis is correlated with tumor thickness (Breslow thickness) in stage I (localized) disease. Metastases, when they occur, typically involve regional lymph nodes first. Frozen sections are not typically used for making a diagnosis of melanocytic lesions, as these lesions are difficult to visualize with frozen techniques.
Excerpted from BCSC 2020-2021 series: Section 4 - Ophthalmic Pathology and Intraocular Tumors. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.