Figure 13-25 Sebaceous carcinoma, histology. A, Tumor cells often have hyperchromatic, atypical nuclei. The cytoplasm frequently has a foamy or vacuolated appearance. Note mitotic figure (arrow). B, Pagetoid invasion of epidermis by individual tumor cells and small clusters of tumor cells (arrows). C, Sebaceous carcinoma in situ with complete replacement of normal conjunctival epithelium by tumor cells (between arrows). (Courtesy of Nasreen A. Syed, MD.)

Treatment recommendations include wide local excision of nodular lesions. Large or deeply invasive tumors may require exenteration. Frozen section control of surgical margins and Mohs micrographic surgery may provide suboptimal results because of difficulty in identifying intraepithelial spread. Permanent margins are often more reliable. Preoperative mapping by routine processing of multiple biopsies may afford a more accurate assessment of the extent of spread of the carcinoma. Survival rates for sebaceous carcinoma are worse than those for squamous cell carcinoma, but they have improved in recent years as a result of increased awareness, earlier detection, more accurate diagnosis, and appropriate treatment. Metastases first involve regional lymph nodes.

For American Joint Committee on Cancer definitions and staging of malignant neoplasms of the eyelid, see the appendix.

Melanocytic Neoplasms

The term nevus may refer to a variety of hamartomatous lesions of the skin or may refer to benign neoplastic proliferations of melanocytic cells. This discussion refers to the latter, melanocytic nevi. Melanocytic nevi commonly occur on the eyelids and may be visible at birth (congenital nevi) or become apparent in adolescence or adulthood. Congenital nevi tend to be larger than those appearing in later years, sometimes reaching substantial size. Nevi greater than 20 cm in diameter are referred to as 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 and result in a “kissing” nevus (Fig 13-26). Nevi in adults often appear as dome-shaped lesions on the eyelid margin.

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 pigment. 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.

Nevi evolve with age and typically begin as macular (flat) lesions. Histologically, these lesions show nests of melanocytes along the epidermal–dermal junction and are consequently termed junctional nevi (Fig 13-27). Clinically, a junctional nevus is indistinguishable from an ephelis, or freckle; but in the latter, the basal layer of epidermal cells contains the pigment. Typically in adolescence, the junctional nests of nevus cells begin to migrate into the superficial dermis, and the nevus becomes increasingly elevated clinically. At this stage, the nevus may increase in pigmentation as well. When both junctional and intradermal components are present, the histopathologic classification becomes compound nevus (Fig 13-28). Finally, sometime in adulthood, the junctional component disappears, leaving only nevus cells within the dermis, and the classification accordingly becomes intradermal nevus (Fig 13-29).

Figure 13-26 Congenital split, or “kissing,” nevus of the eyelid.

Figure 13-27 Junctional nevus. Nests of nevus cells are seen at the junction between epidermis and dermis.

An evolution in the cytomorphology of the nevus cells also takes place: those in the superficial portion of the nevus are polygonal, or epithelioid, in shape (type A nevus cells). Within the midportion of the nevus, the cells become smaller, have less cytoplasm, and resemble lymphocytes (type B nevus cells). At the deepest levels, the nevus cells become spindled and appear similar to Schwann cells of peripheral nerves (type C nevus cells). Recognition of this “maturation” is useful in classifying melanocytic neoplasms as benign. Multinucleated giant melanocytes and interspersed adipose tissue are common in older nevi.

Figure 13-28 Compound nevus. Nests of nevus cells are present in the dermis (arrows) as well as at the junction of epidermis and dermis (arrowheads).

Figure 13-29 Intradermal nevus. The nests of nevus cells are confined to the dermis.

Nevi that show some clinical or pathologic atypicality include the Spitz nevus and the dysplastic nevus. Spitz nevi develop in late childhood or in adolescence and are uncommon after the second decade. In contrast to the clinical picture of the usual nevus, they may be larger (up to 1.0 cm) and have a tan-pink color. Histologically, they are usually compound and exhibit nuclear and cytoplasmic enlargement and pleomorphism, features suggesting malignancy. Other features suggesting malignancy, however, such as atypical mitotic figures, intraepidermal migration, and lack of maturation, are generally lacking.

Clinical features suggesting a dysplastic nevus may include size greater than 0.5 cm, irregular margins, and irregular pigmentation. Cytologic atypia is characterized by nuclear enlargement and hyperchromasia and prominent nucleoli. Clinically suspicious lesions should be completely excised. Persons with multiple dysplastic nevi are at increased risk for development of melanoma and may represent a genetic susceptibility, suggesting that family members should also be examined and observed closely.

Cutaneous melanoma is a rare occurrence on the eyelids. It may be associated with a preexisting nevus, or it may develop de novo. Clinical features suggesting malignancy are the same as those just mentioned for dysplastic nevi; in addition, invasive melanoma is heralded by a vertical (perpendicular to the skin surface) growth phase that results in an elevated or indurated mass. There are 4 main histologic subtypes of melanoma:

superficial spreading lentigo maligna nodular acral-lentiginous

Superficial spreading is the most common type of cutaneous melanoma and demonstrates a radial (intraepidermal) growth pattern extending beyond the invasive component. Lentigo maligna melanoma occurs on the face of elderly individuals, with a long preinvasive phase, and is the most common type occurring on the eyelids. Acral-lentiginous melanoma, as the name implies, involves the extremities and is not seen on the eyelids (Fig 13-30).

Figure 13-30 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, Acrallentiginous melanoma is similar to lentigo maligna melanoma, but atypical melanocytes are also present in the more superficial layers of the epidermis. C, 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, acrallentiginous, and superficial spreading melanomas spread horizontally (radial growth) through the skin, staying close to the epidermal–dermal junction. D, Nodular melanoma has a narrow intraepidermal component and more prominent vertical growth within the dermis; it is therefore more deeply invasive compared with the other types. (Modified with permission from

Spencer WH, ed. Ophthalmic Pathology: An Atlas and Textbook. Vol 4. Philadelphia: WB Saunders; 1996:2270. Illustration by Christine Gralapp.)

Histologic features characteristic of melanoma include pagetoid intraepidermal spread of atypical melanocytic nests and single cells, nuclear abnormalities as listed earlier, 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 depth of invasion (Breslow depth) in stage I (localized) disease. Metastases, when they occur, typically involve regional lymph nodes first.