Lentigo management


National report — Treatment with the topical immune response modifier imiquimod 5 percent cream (Aldara, 3M Pharmaceuticals) may have a role in the management of lentigo maligna (LM), but perhaps only as an adjunct to staged surgical excision, said Murray Cotter, M.D., Ph.D., at the 63rd Annual Meeting of the American Academy of Dermatology.

Work in progress Dr. Cotter and colleagues from the University of Utah Medical Center, Salt Lake City, conducted a pilot study evaluating treatment of LM with imiquimod prior to staged excision. Dr. Cotter is a dermatology resident. His collaborators in this study were Glen M. Bowen, M.D., assistant professor of dermatology, and Jeffrey McKenna, M.D., visiting instructor.

They enrolled 19 patients with biopsy-proven LM who applied imiquimod daily for three months and then, after a two-month waiting period, underwent staged excision of the treated area using a 2 mm margin.

"This is a work in progress, and further study is needed to evaluate the role of imiquimod for the treatment of LM," Dr. Cotter says. "However, the results of this study, combined with previous reports demonstrating the possibility of clinicopathologic discordance, indicates caution is warranted in relying on imiquimod as monotherapy. Rather, it may be safe for the treatment of LM only as an adjunct to surgical extirpation."

Alternative to surgery?

Since LM often develops in cosmetically sensitive areas, topical imiquimod has been investigated as an alternative for avoiding surgery.

"The gold standard of therapy for LM is wide excision with 5 mm margins," Dr. Cotter explains. "However, LM lesions often have subclinical extension beyond the 5 mm clinical margin. For that reason, and because most of these lesions are present in cosmetically sensitive areas, surgical excision can be cumbersome."

Previous case reports and two case series show imiquimod is often effective in achieving clinical and histological resolution of LM lesions. However, similar to the results of this study, there has also been a prior description of invasive disease developing over the course of treatment with imiquimod as well as a case where there was clinical resolution with no histologic change.

"Given that background and the potential for sampling error with biopsy, we thought staged excision after imiquimod would be a good opportunity to provide patients with standard of care while also providing an opportunity to histologically evaluate lesions treated with imiquimod," Dr. Cotter says.

The patients included in the study were generally older (mean age, 70 years) and had biopsy-proven LM in sites that could not be readily excised. The lesions were mostly on the face, including the cheek and nose in 11 cases.

Patients were instructed to apply imiquimod to the pigmented lesion and extending a few centimeters beyond the visible margins. Application frequency began with daily use, but was titrated based on erythema.

After completing the course of imiquimod, 15 (78.9 percent) of the 19 patients had a complete clinical response with no residual pigment, and the remaining patients were categorized as having a partial clinical response defined by reduction in pigment. Staged excision surgery using 2 mm margins was delayed for two months to allow inflammation to resolve and enable the ability of the dermatopathologist to read the paraffin-embedded sections accurately.

Larger study needed After the first excision, 17 (89.5 percent) of 19 lesions had histologically clear margins, while the remaining two patients required two stages to achieve clear margins.

"In a previous study undertaken at the University of Utah, an average of 2.6 stages of surgery performed with a 5.0 mm margin was needed to achieve clear margins for LM lesions not treated with imiquimod," Dr. Cotter says. "The results achieved with imiquimod compared with historical controls suggests that a larger, randomized study should be performed comparing surgery alone against surgery plus imiquimod."

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