Malignant Tumors of the Eyelid

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 removed by shave biopsy.
Chalazion/hordeolum: Acute, erythematous, tender, well-circumscribed lesion. See 6.2, 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.

Etiology ⬆ ⬇

Basal cell carcinoma: Most common malignant eyelid tumor, usually on the lower eyelid or medial canthus of 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. Sometimes the lesion center is ulcerated (see Figure 6.11.1). On rare occasions, a cystic variant is seen.
- Infiltrative: The classic variant of this form is the morpheaform lesion. A firm, flat, subcutaneous lesion with indistinct borders. More difficult to excise and may result in a large eyelid defect.
6-11.1 Basal cell carcinoma.
Squamous cell carcinoma: Variable presentation, often appearing 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.
Keratoacanthoma: This lesion was previously considered to be benign and self-limiting; however, it is now regarded as a low-grade squamous cell carcinoma. Clinically may resemble basal and squamous cell carcinomas. 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 confused with recurrent chalazia 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 6.11.2).
Others: Malignant melanoma, lymphoma, sweat gland carcinoma, metastasis (usually breast or lung), Merkel cell tumor, Kaposi sarcoma, and others.

6-11.2 Sebaceous carcinoma.

Work Up ⬆ ⬇

Workup

History: Duration? Rapid or slow growth? Previous malignant skin lesion or other malignancies? Previous treatment of inflammatory or allergic condition? Previous radiation therapy? Associated pain?
External examination: Check the skin for additional lesions, palpate the preauricular, submaxillary, and cervical nodes to evaluate for metastasis.
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.
Photograph or draw the lesion and its location for documentation.
Perform a biopsy of the lesion. An incisional biopsy is commonly performed when a malignancy is suspected. Depending on the depth of invasion, sentinel node biopsy may be indicated with melanoma and sebaceous carcinoma. Histopathologic confirmation must precede any extensive procedures.
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.
For lymphoma, the pathologist would prefer the tissue to be sent fresh for flow cytometry. Contact the pathologist first. If confirmed, a systemic workup is indicated. See 7.4.2, ORBITAL TUMORS IN ADULTS.

Treatment ⬆ ⬇

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 can be treated by the oral Hedgehog pathway inhibitor vismodegib, although it is expensive and can cause systemic side effects. Patients are informed about the etiologic role of the sun and are advised to avoid unnecessary sunlight exposure and to use protective sunscreens.
Squamous cell carcinoma: Surgical excision is considered as first-line treatment. Radiation therapy is the second-best treatment after surgical excision. Topical imiquimod and topical or injectable interferon can be beneficial for elderly patients who are not surgical candidates. Patients are informed about the etiologic role of the sun. Referral to an oncologist or internist for regional and/or systemic workup and surveillance is important.
Sebaceous carcinoma: The approach is two-staged with stage 1 using map biopsies on the entire surface of the eye to ascertain the extent of Pagetoid spread or deep tumor. Stage 2 is performed after all biopsies are reviewed; Pagetoid spread is treated with cryotherapy whereas deep tumor requires excision. Reconstruction is then provided. Close follow up of regional nodes is indicated. Exenteration is often required when orbital invasion is present. Referral to an oncologist or internist for systemic workup and surveillance is important with attention to the lymph nodes, lungs, brain, liver, and bone.
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 or internist for regional and/or systemic workup and surveillance is imperative.

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 or temporary tarsorrhaphy.

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Symptoms ⬇

Signs ⬆ ⬇

Differential Diagnosis ⬆ ⬇

Etiology ⬆ ⬇

Work Up ⬆ ⬇

Treatment ⬆ ⬇

Follow Up ⬆