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Malignant melanoma of the eyelids an increasing threat
Different sized surgical margins should be used to treat tumors of varying thickness.
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There is a 4% increase in the rate of malignant melanoma diagnosed each year. There were 51,400 new melanoma cases diagnosed in 2002 with 7,800 deaths. The lifetime risk in the United States of developing a melanoma is 1 in 71, while in Australia the chance is 1 in 14 to 17. Twenty-five percent of malignant melanoma patients are under 40 years of age.
Melanoma issues are related to ozone depletion, clothing styles, sunscreens and UV light, sunscreens and nevi protection, and episodic exposure vs. cumulative exposure to sun. Blistering sunburns are to be avoided, especially by patients with fair complexions.
Those most at risk for developing melanoma are familial groups, patients with dysplastic nevus, and patients with a high number of moles.
The high-risk groups are patients with xeroderma pigmentosa, patients who have had multiple PUVA treatments, patients with cutaneous T-cell lymphoma or non-Hodgkin’s lymphoma, and patients with organ transplants or AIDS. Melanoma patients have a fivefold increased risk of developing a second melanoma.
Malignant melanomas represent 5% of cutaneous cancers and less than 1% of malignant lesions of the eyelid. Melanomas may develop de novo, from existing melanocytic nevi or from lentigo maligna. There are four clinicopathologic forms of cutaneous melanoma: lentigo maligna melanoma, nodular melanoma, superficial spreading melanoma and acrolentiginous melanoma, which does not involve the eyelid.
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The typical characteristics of malignant melanoma are variable pigmentation (that is, a lesion with shades of brown, red, white, blue or dark black), irregular borders, ulceration and bleeding (Fig. 1). Eyelid melanomas involving the conjunctiva are usually more aggressive than those confined to the eyelid skin.
Lentigo maligna melanoma
Lentigo maligna melanoma represents the invasive vertical malignant growth phase that occurs in 30% to 50% of patients with lentigo maligna (Fig. 2). Lentigo maligna is a melanoma with in situ characteristics, and it accounts for 90% of head and neck melanomas.
Vazira found more cases of lentigo maligna melanoma, both in situ and invasive of the eyelid, than other histologic types of melanoma. This differs from two other comparable studies. Grossniklaus and McLean, excluding in situ cases, found 59% of eyelid melanomas to be nodular melanoma, 22% to be superficial spreading melanoma and 19% to be lentigo maligna melanoma. Garner and co-workers had no cases of lentigo maligna melanoma of the eyelid, but 50% of their eyelid cases were nodular melanoma (Fig. 3). Vazira and Grossniklaus found that men and women were equally affected and that the lower eyelid is most frequently involved. However, Garner found that women are affected more often and that the upper eyelid is more commonly involved.
Measurements
Two methods, described by Clark and Breslow, are used to express the depth of invasion in malignant melanoma.
Clark and colleagues divided the depth of invasion into five anatomic levels. Level 1 is confined to the epidermis (in situ). Level 2 penetrates the papillary dermis. Level 3 fills the papillary dermis. Level 4 extends to the reticular dermis. Level 5 tumors extend into the subcutaneous tissue. Level 4 or Level 5 malignant melanoma of the eyelid skin usually means a poor prognosis.
Breslow developed a quantitative method that measures the depth of invasion in millimeters. Patients with tumors less than 0.75-mm thick have an excellent prognosis with a 5-year survival of 100%. Patients with lesions that are 0.75-mm to 1.5-mm thick have a fair prognosis, and patients with tumors more than 1.5-mm thick have a poor prognosis with a 5-year survival of 50% to 60%.
The World Health Organization’s melanoma program carried out a prospective randomized study in the 1980s to determine whether the use of narrow surgical margins for invasive melanomas (less than 2 mm) affect outcome.
One group was treated with 1-cm surgical margins and the other group with 3-cm surgical margins. After a mean follow-up of 90 months, there was no difference between the groups in the disease-free or overall survival rate. A higher recurrence rate was found in patients who had malignant melanomas that were 1-mm thick or more and had a 1-cm surgical margin. No patient with a malignant melanoma thinner than 1 mm with a 1-cm surgical margin had a recurrence.
Therefore, it was recommended that a malignant melanoma that is less than 1 mm in Breslow thickness have a 1-cm surgical margin, and a malignant melanoma between 1 mm and 2 mm be excised with a 3-cm surgical margin. In recent years, this has been modified by the American Joint Committee on Cancer. They suggest that in situ melanoma should have an 0.5-cm margin; less that 2-mm thick, a 1-cm margin; and greater than 2-mm thick, a 2-cm margin.
Biopsy and mapping
Most recently, sentinel node biopsy and lymph node mapping have become standards of care for staging of medium thickness malignant melanomas with a propensity for regional lymph node metastasis.
Various authors have studied the effectiveness of using both an intraoperative gamma detecting probe and a vital blue dye to localize the sentinel node after injection of technetium-99 and the vital blue dye around the site of the melanoma or the site of the excision. A combination of the techniques localizes the sentinel lymph node reliably and the draining nodal basin in 96% to 100% of patients. Although the occurrence of malignant melanoma in the eyelid is uncommon and the number of sentinel cases small, the technique may prevent unnecessary radical neck dissection.
Sentinel lymph node biopsy is based on the clinical observation that most malignancies with the potential for lymphatic spread metastasize sequentially within the dermal lymphatics: that is, they metastasize to the nearest node in the regional lymphatic drainage basin before disseminating to more distant nodes.
Results of prospective randomized clinical trials designed to evaluate lymph node dissection in melanomas of the head and neck have shown no benefit with early dissection of regional nodes. On the other hand, postponement of lymph node dissection until patients develop clinical evidence of regional lymph node involvement may permit the spread of melanoma to multiple and distant sites before clinical detection, resulting in poor chances of survival.
The technique of lymphatic mapping and sentinel lymph node biopsy has shown promise as a noninvasive method for determining which patients have microscopic regional node metastasis. Sentinel lymph node biopsy is best suited for lesions with a high risk to metastasize to regional lymph nodes. For medium thickness melanomas (1.5 mm to 4 mm), the rate of sentinel lymph node positivity is around 15%, according to large-scale, multicenter studies. According to recent retrospective series, malignant melanoma of the periocular area metastasizes to the regional lymph nodes in up to 29% of patients.
Complete surgical dissection of the involved lymphatic basin can be performed, and adjuvant therapy may be appropriate for patients with a positive sentinel lymph node. The therapy consists of radiation to the regional nodal basin, systemic administration of interferon chemotherapy or a combination of both.
For Your Information:References:
- Mark R. Levine, MD, FACS, is a clinical professor of ophthalmology, Department of Ophthalmology, Case Western Reserve University. He can be reached at University Suburban Health Center, 1611 South Green Rd, Suite 306A, South Euclid, OH 44121; (216) 291-9770; fax: (216) 291-0550.
- Cooper K. Melanoma Update 2002, University Hospitals of Cleveland. October 23, 2002.
- Vazira M, Buffam FV, et al. Clinicopathologic features and behavior of cutaneous eyelid melanoma. Ophthalmology. 2002;109(5):901-908.
- Grossniklaus HE, McLean W. Cutaneous melanoma of the eyelid. Ophthalmology .1991;98(12):1867-1873.
- Garner A, Koorneef L, Levene A, Collin JRO. Malignant melanoma of the eyelid skin: histopathology and behavior. Br J Ophthalmol. 1985;69:180-186.
- Breslow A, Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg. 1970;172:902-908.
- Clark, WH Jr, From L, Bernadino EA, et al. The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res. 1969;29:705-727.
- Cook BE, Bartley GB. Treatment options and future prospects for the management of eyelid malignancies. Ophthalmology. 2001;108(11):2088-2099.
- Esmaeli B. Sentinel node biopsy as a tool for accurate staging of eyelid and conjunctival malignancies. Current Opinions. Ophthalmology. 2002;13:317-323.
- Esmaeli B, Wang B, et al. Prognostic factors for survival in malignant melanoma of the eyelid skin. Ophthalmol Plastic & Recon Surg. 2000;16(4):250-257.