Eyelid Malignancies

Epidemiology and Pathogenesis

BCC is the most common malignant tumor of the eyelids and constitutes 85%–90% of all malignant epithelial eyelid tumors at this site. Over 99% of BCCs occur in white people; about 95% of these lesions occur between the ages of 40 and 79 years, with an average age at diagnosis of 60 years. Rarely, they also may be seen in children. BCC arises from a pluripotential stem cell in the epidermis that proliferates, amplifies, and eventually terminally differentiates. Proposed mechanisms for BCC invasion include enhanced tumor cell motility and collagenase content. Having had one BCC is a prognostic factor for the development of additional lesions.

Ocular Manifestations

Up to 50%–60% of BCCs affect the lower eyelid. The medial canthus is involved 25%–30% of the time. The upper eyelid is involved nearly 15% of the time, and the lateral canthus is only rarely involved (5%). On the basis of their histopathological presentation, BCCs may be classified into six basic types:

• Nodular-ulcerative

• Pigmented

• Morphea or sclerosing

• Superficial

• Fibroepithelioma

• Infundibulocystic

Micronodular and basosquamous are two additional descriptors with primarily histopathological as well as therapeutic and prognostic significance.

The nodular type of BCC, the most common lesion, has the classical appearance of a pink or pearly papule or nodule with overlying telangiectatic vessels. As the nodule grows in size, central ulceration may occur, surrounded by a rolled border ( Fig. 12.8.1 ). This appearance is often described as a “rodent ulcer.”

The pigmented BCC is similar to the noduloulcerative type in morphology but with brown or black pigmentation. These lesions represent the most common pigmented malignancy on the eyelids and may resemble malignant melanoma.

The morphea or sclerosing type of BCC appears as a flat, indurated, yellow–pink plaque with ill-defined borders. It may simulate a blepharitis or dermatitis. Because it has a flat appearance, it may not be as clinically noticeable as others. However, this form of BCC is aggressive and may invade the dermis deeply. It characteristically occurs in the medial canthal region and may invade the paranasal sinuses and orbit.

Superficial BCC appears as an erythematous, scaling patch with a raised pearly border. Fibroepithelioma BCC presents as a pedunculated or sessile smooth, pink nodule and primarily arises on the trunk rather than the eyelid.

Infundibulocystic BCC appears as a well-circumscribed pearly papule commonly found on the head and neck of the elderly. Basosquamous types represent well-defined nodular or superficial BCC overlying an invasive front showing BCC as well as squamous cell carcinoma histological features. Micronodular BCC presents as an erythematous macule or thin papule and histologically presents as multiple small aggregates of basaloid cells within the dermis.

Diagnosis

The diagnosis of BCC is initially made from its clinical appearance, especially with the noduloulcerative type with its raised pearly borders and central ulcerated crater. Definitive diagnosis, however, can be made only on histopathological examination of biopsy specimens.

Differential Diagnosis

The differential diagnosis of BCC and of other periocular malignant lesions may be divided into several categories: other malignant lesions, premalignant lesions, benign adnexal tumors and cysts, and inflammatory and infectious conditions ( Table 12.8.1 ; see Chapter 12.14 ). In many cases the diagnosis depends on histopathology.

Systemic Associations

Basal cell nevus syndrome (Gorlin–Goltz syndrome) is inherited as an autosomal-dominant disorder with high penetrance and variable expressivity. Basal cell nevus syndrome is rare, occurring in less than 1% of individuals with BCC. The group of clinical findings described in 1960 as a syndrome by Gorlin and Goltz includes the following:

• Multiple BCCs affecting the face, trunk, and extremities

• Cysts of the jaw (odontogenic keratocysts)

• Skeletal abnormalities (e.g., bifid ribs)

• Neurological abnormalities (e.g., mental retardation, ectopic calcification, cerebellar medulloblastoma)

• Endocrine disorders (e.g., ovarian cysts and testicular disorders)

Palmar and plantar pits also develop in young adulthood. The BCCs in this syndrome typically develop at puberty and have a predilection for the periorbital region and face. Multiple lesions occur with a high rate of recurrence. Other rare BCC syndromes include Bazex syndrome, linear unilateral basal cell nevus, and Rombo syndrome.

Also, BCC may be associated with albinism, xeroderma pigmentosum, and nevus sebaceous.

Pathology

The BCCs may be grouped as either undifferentiated or differentiated by their histopathological appearance. The typical histopathology of an undifferentiated BCC consists of nests, lobules, and cords of tumor cells with peripheral palisading of cells and stromal retraction ( Fig. 12.8.2 ). Undifferentiated BCCs include the solid noduloulcerative, morphea or sclerosing, pigmented, superficial, and fibroepithelioma forms. The morphea or sclerosing form is characterized by strands of proliferating, malignant basal cells in a fibrous stroma ( Fig. 12.8.3 ).

The adenoid and metatypical or basosquamous are the most common differentiated forms. These tumors differentiate toward glandular structures with mucinous stroma. They exhibit morphological features between those of basal cell and squamous cell carcinoma. The metatypical BCCs are more aggressive and invasive, with a higher recurrence rate and potential for metastasis.

Treatment

The goal of therapy is the complete removal of tumor cells with preservation of unaffected eyelid and periorbital tissues. Although nonsurgical treatments such as cryotherapy, electrodesiccation, and laser ablation are advocated by some, surgical therapy is the generally accepted treatment of choice for the removal of BCCs. Some BCCs, especially the morphea and multicentric types, may extend far beyond the area that is apparent clinically. Recurrences are generally more aggressive, infiltrative, and destructive than the primary tumor. Therefore histological monitoring of tumor margins is essential. Mohs’ micrographic surgery and excisional biopsy with frozen section control are the two basic techniques available. An incisional biopsy may be performed before definitive treatment to confirm the clinical suspicion of BCC.