Asymptomatic or mildly irritating eyelid lump.

Skin ulceration and inflammation with distortion of normal eyelid anatomy. Abnormal color, texture, or persistent bleeding. Loss of eyelashes (madarosis) or whitening of eyelashes (poliosis) over the lesion. Sentinel vessels may be seen. Diplopia or external ophthalmoplegia are ominous signs of a possible orbital invasion.

Differential Diagnosis of Benign Eyelid Tumors

• Seborrheic keratosis: Middle-aged or elderly patients. Brown-black, well-circumscribed, crust-like lesion, usually slightly elevated, with or without surrounding inflammation. May be monitored or excised.

• Chalazion/hordeolum: Acute, erythematous, tender, well-circumscribed lesion. See 6.7, Chalazion/Hordeolum.

• Cysts: Well-circumscribed white, yellow, or clear/skin-colored lesions on the eyelid margin or underneath the skin. Epidermal inclusion cysts, sebaceous cysts, and eccrine or apocrine hidrocystomas, may be excised.

• Molluscum contagiosum: A viral infection of the epidermis, typically seen in children. Multiple small papules characterized by central umbilication. Can be severe in HIV-positive patients. May produce a chronic follicular conjunctivitis. Treatment is by unroofing and curettage. While some recommend curettage until bleeding occurs, there is no clear evidence that this is more effective. A variety of other therapies (e.g., cryotherapy, cautery, chemical peel, and laser) are used for lesions found elsewhere on the body but are typically not necessary for periocular regions and may cause injury to the ocular surface. See 5.2, Chronic Conjunctivitis.

• Nevus: Benign melanocytic neoplasm, which may involve the dermis, the dermis–epidermis junction, or both. Congenital nevi may be present at, or shortly after, birth; however, most nevi appear during childhood and may  enlarge during puberty. Nevi are well-circumscribed lesions, usually round or oval, with uniform pigmentation. Melanomas may develop within preexisting nevi and may manifest as a changing pigmented lesion and/or as a pigmented lesion with asymmetry of shape, irregular borders, color variegation, and possibly pruritus or bleeding. Suspicious lesions should be biopsied, preferably with the removal of the entire lesion to the subcutaneous fat.

• Xanthelasma: Multiple, often bilateral, soft yellow plaques of lipid-laden macrophages in the medial upper and sometimes lower eyelids. Patients 40 years and younger should have a serum cholesterol and lipid profile evaluation to rule out hypercholesterolemia. Surgical excision can be performed for cosmesis; however, recurrence is possible.

• Squamous papilloma: Soft, skin-colored lesions that may be smooth, rounded, or pedunculated. May enlarge or multiply over time. Often spontaneously regress. Occasionally squamous carcinomas can appear papillomatous. Therefore, excisional biopsy should be performed for suspicious lesions.

• Actinic keratosis: Round, erythematous, premalignant lesion with a scaly surface. Found in sun-exposed areas of skin. Treated by excisional biopsy.

• Inflammatory conditions: Blepharitis and blepharoconjunctivitis.

• Allergic conditions: Chronic contact dermatitis can appear unilateral, cause cilia loss, and simulate malignancy.

• Others: Verrucae from human papillomavirus, benign tumors of hair follicles, or sweat glands (e.g., syringoma), inverted follicular keratosis, neurofibroma, neurilemmoma, capillary hemangioma, cavernous hemangioma, and pseudoepitheliomatous hyperplasia. Necrobiotic xanthogranuloma nodules of multiple myeloma appear as yellow plaques or nodules that are often mistaken for xanthelasma.

• Basal cell carcinoma: Most common malignant eyelid tumor, often present in the medial canthus or the lower eyelid in middle-aged or elderly patients. Rarely metastasizes, but may be locally invasive, particularly when present in the medial canthal region. There are two major forms:

  • Nodular: Indurated, firm mass, commonly with telangiectasias over tumor margins (see Figure 6.8.1).

    Figure 6.8.1: Basal cell carcinoma.

    

  • Infiltrative: The classic variant of this form is the morpheaform lesion. A firm, flat, subcutaneous lesion with indistinct borders. More difficult to excise due to the lack of visibly discrete margins, and may result in a large eyelid defect.

• Squamous cell carcinoma (SCC): Variable presentation, may appear clinically similar to basal cell carcinoma. Regional metastasis may occur and can be extensive with the propensity for perineural invasion. A premalignant lesion, actinic keratosis, may appear either as a scaly, erythematous flat lesion or as a cutaneous horn, and can progress to SCC.

• Keratoacanthoma: This lesion was previously considered to be benign and self-limiting;  however, it is now regarded as a low-grade SCC. Clinically may resemble basal and SCCs. Typically, the lesion is elevated with rolled margins and a large central ulcer filled with keratin. Rapid growth with slow regression and even spontaneous resolution has been observed. Lesions usually involve the lower eyelid and can be destructive. Complete excision is recommended.

• Sebaceous carcinoma: More common in middle-aged or elderly patients, usually elderly women. Most common on the upper eyelid but may be multifocal, involving both the upper and the lower eyelids. Often mistaken for a recurrent chalazion or intractable blepharitis. Loss of eyelashes and destruction of the meibomian gland orifices in the region of the tumor may occur. Regional and systemic metastasis or orbital extension is possible. Can occur many decades after prior radiation exposure to the eyelids (see Figure 6.8.2).

  Figure 6.8.2: Sebaceous carcinoma.

  

• Others: Malignant melanoma, lymphoma, sweat gland carcinoma, metastasis (usually breast or lung), Merkel cell tumor, Kaposi sarcoma, and others.

1. History: Duration? Rapid or slow growth? History of extensive sun exposure? Previous malignant skin lesion or other malignancies? Previous treatment of inflammatory or allergic condition? Previous radiation therapy? Associated pain?

2. External examination: Check the skin for additional lesions, palpate the preauricular, submaxillary, and cervical nodes to evaluate for metastasis.

3. Slit-lamp examination: Look for telangiectasias on nodular tumors, loss of eyelashes in the region of the tumor, and meibomian orifice destruction. Evert eyelids of all patients with eyelid complaints.

4. Photograph or draw the lesion and its location for documentation.

5. Perform a biopsy of the lesion. An incisional biopsy is commonly performed when a malignancy is suspected. Depending on the size and depth of invasion, sentinel lymph node biopsy may be indicated with melanoma and sebaceous carcinoma. Histopathologic confirmation must precede any extensive procedures.

6. Sebaceous carcinoma may be difficult to diagnose histopathologically. In the past, fresh tissue with oil red-O staining was recommended. This is no longer necessary if the pathologist is experienced with this malignancy.

7. For suspected lymphoma, tissue should be sent fresh for flow cytometry in addition to the formalin fixed sample. Contact the pathologist to inform of clinical suspicion. If confirmed, a systemic workup is indicated. See 7.4.2, Orbital Tumors in Adults.

1. Basal cell carcinoma: Surgical excision with histologic evaluation of tumor margins either by frozen sections or by Mohs techniques. The entire tumor should be excised with clean margins. Cryotherapy and radiation are used rarely. Topical imiquimod, an immune modulator, might be beneficial but could be toxic to the ocular surface. Unresectable tumors, patients with numerous tumors or recurrences, or those that would require extensive, disfiguring resection for tumor clearance can be treated by the oral Hedgehog pathway inhibitors (e.g., vismodegib and sonidegib) although their use may be limited by systemic side effects. Patients are informed about the etiologic role of the cumulative sun exposure and are advised to follow closely with dermatology for monitoring of cancers elsewhere on the skin.

2. SCC: Complete surgical excision is considered as first-line treatment. Histology can be used to confirm tumor-free margins, using either Mohs’ micrographic surgery or excision with frozen-section control. In cases of large tumors or where perineural invasion or recurrent lesions are suspected, patients may benefit from sentinel lymph node biopsy with radical dissection. Distant metastasis should be ruled out. Medical therapy can be pursued if the patient is not a surgical candidate or the disease is considered unresectable or would result in unacceptable morbidity. Medical treatment options include epidermal growth factor receptor inhibitors (e.g., gefitinib, erlotinib, and cetuximab) as well as immune checkpoint (e.g., PD-1) inhibitors. At present, radiation is reserved for refractory or unresectable cases, such as cases of perineural invasion, or as adjuvant therapy. Topical imiquimod and topical or injectable interferon can be beneficial for elderly patients who are not surgical candidates and in whom disease is limited to the ocular  surface. Referral to an oncologist or internist for advanced disease and systemic workup may be necessary. Patients are informed about the etiologic role of the cumulative sun exposure and are advised to follow closely with dermatology for monitoring of cancers elsewhere on the skin.

3. Sebaceous carcinoma: The surgical approach may be separated into two stages. The first stage utilizes map biopsies of the entire surface of the eye to ascertain the extent of Pagetoid spread or deep tumor invasion. The second stage of definitive resection is performed after all biopsies are reviewed; Pagetoid spread on the ocular surface may be treated with cryotherapy, and eyelid involvement is managed with resection and reconstruction. Close follow-up for recurrent ocular surface disease is necessary as well as surveillance of regional lymph nodes with possible sentinel lymph node biopsy based on tumor size. Exenteration may be necessary when orbital invasion is present. Referral to an oncologist for systemic workup and surveillance is important with attention to the lymph nodes, lungs, brain, liver, and bone.

4. Malignant melanoma: Treatment requires wide surgical excision. The margins must be free of tumor and require permanent sections. Sentinel lymph node biopsy may be required depending on tumor depth. Referral to an oncologist for regional and/or systemic workup and surveillance is imperative. BRAF and MEK inhibitors may be used for unresectable or metastatic disease.

NOTE Because both melanoma and sebaceous carcinoma are difficult to diagnose by frozen section, multiple excisions utilizing permanent sectioning may be necessary until all surgical margins are free of tumor. The cornea and globe must be protected during this interim time with lubrication, patching, and/or temporary tarsorrhaphy.

Initial follow-up is every 1 to 4 weeks to ensure proper healing of the surgical site. Patients are then reevaluated every 3 months initially. Patients who have had one skin malignancy are at greater risk for additional malignancies.