Plastic and Reconstructive Surgery - Global Open:
Gassman, Andrew A. MD*; Yuan, Joyce MD†; Koh, Justin BA†; Miller, Timothy A. MD, FACS*
From the *Division of Plastic and Reconstructive Surgery, Department of Surgery, UCLA David Geffen School of Medicine, Los Angeles, Calif.; and †UCLA David Geffen School of Medicine, Los Angeles, Calif.
Received for publication October 6, 2013; accepted December 4, 2013.
Disclosure: The authors have no financial interest to declare in relation to the content of this article. The Article Processing Charge was paid for by the Division of Plastic and Reconstructive Surgery, Department of Surgery, UCLA David Geffen School of Medicine, Los Angeles, California.
Andrew A. Gassman, MD, UCLA Department of Surgery, Division of Plastic & Reconstructive Surgery, David Geffen School of Medicine, 200 UCLA Medical Plaza, Suite 465, Los Angeles, CA 90095–6960, E-mail: email@example.com
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Summary: We present a brief literature review of the topical immune-modulating medication Imiquimod. The treatment of periorbital melanoma in situ typically requires surgical resection. Here we discuss a case of lower eyelid melanoma in situ successfully treated non-operatively with Imiquimod.
The National Comprehensive Cancer Network currently recommends that intraepidermal melanoma known as either melanoma in situ or lentigo maligna undergo local resection.1 The smallest acceptable surgical excision margin for these lesions is 0.5 cm.2 Removal of a melanoma in situ of any substantial size specifically in the lower eyelid would therefore create a defect that poses formidable reconstructive challenges. Some authors have supported micrographic surgery to minimize the surgical defect and3,4 those same authors indicate that the standard 0.5 cm surgical margins may be, in fact, inadequate. We agree.
Imiquimod (R-837, S-26308) is a topical cream used clinically approved to treat genital warts, actinic keratosis, and superficial basal cell carcinoma. Imiquimod was developed in the 1980s for herpes virus treatment, and its ability to increase proinflammatory cytokine synthesis and nonspecific B cell production was later characterized during clinical trials.5 It is the leading member of the imidazoquinoline family (eg, Resiquimod), low-molecular-weight compounds with immunopotentiatory effects. Subsequent studies have noted Imiquimod’s immunomodulating and antitumor effects on a myriad of dermatologic disorders.
Imiquimod has been examined in the management of lentigo maligna through several studies in the past decade, examining its effects before staged excision, after complete excision, and in isolation for histologically confirmed cases of lentigo maligna. These studies reported clearance rates ranging from 77% to over 90%, depending on the specific cohorts involved. The study with the highest reported success was based on daily applications at least 2 cm beyond suspected tumor margins.6,7 Most of these small trials reported a 0% incidence of recurrence following Imiquimod treatment—1 patient who showed a recurrent lesion was successfully retreated with Imiquimod.8 Recently there has been rapidly increasing interest in using this medication to treat both premalignant and malignant lesions in critical areas where excision would result in formidable challenges for surgical reconstruction.
Reconstruction for the lower eyelid is a particularly daunting task as the surgeon must reconstruct highly visible and functional tissue comprised of the body’s thinnest skin. Compared with tarsomarginal grafts (the Hübner technique involving a pentagonal full-thickness graft from the contralateral eyelid) or local tissue advancement/rearrangement, topical Imiquimod offers a superior cosmetic result without a single scar or tissue discoloration. This report describes a scarless, successful treatment of a lentigo maligna that occupied the majority of the lower eyelid.
We present a 68-year-old woman with a dark lesion of varying shades of gray of her left lower eyelid (Fig. 1). She noted a gradual increase in size until the discoloration extended beyond the ciliary margin and involved over 60% of her lower lid. She denied pain and sought attention after attempting to conceal the lesion for several months with makeup. No lymphadenopathy or other clinical findings were noted. A full-thickness biopsy was performed that revealed melanoma in situ, lentigo maligna type (Fig. 2). Treatment began with modest amounts of topical Imiquimod applied every third day to the entire affected lower eyelid. By the fifth application, erythema appeared around and then within the lesion itself (Fig. 3). At approximately 3 weeks, an ulcer formed in the area of darkest pigmentation (lateral lower eyelid) and a slight ectropion seemed (Fig. 1). Treatment extended for another 3 weeks and was then discontinued. As healing continued, normal skin appeared. Two months later, an excisional biopsy taken from the same site as the first biopsy in the most lateral extent of the eyelid showed no tumor present (Fig. 1). Six weeks later, the eyelid seemed entirely normal with pigmentation matching the contralateral side, no ectropion, no ulceration, and no erythema (Fig. 1).
We are not the first to describe this application. The use of Imiquimod in the treatment of periorbital lentigo maligna has been cited several times in both dermatologic and ophthalmologic literature.3,9–11 However, these findings represent several case reports or small series that had large variations in treatment protocols. The only consistent finding in each of these cases and our own is that by 6 months after the initiation of topical Imiquimod therapy, all lesions underwent complete resolution. Imiquimod is a powerful tool in the treatment of dermatologic disorders.
Lentigo maligna requires full-thickness skin excision. This approach creates a difficult reconstructive challenge in delicate areas such as the lower eyelid. Imiquimod, an immunomodulating Toll-like receptor agonist, has been Food and Drug Administration approved for the treatment of genital/perianal warts, actinic keratosis, and superficial basal cell carcinoma. Imiquimod’s off-label use in the treatment of lentigo maligna is currently under investigation. This report and earlier case series demonstrate that it is a useful to treat the intraepidermal melanoma to resolution without the creation of secondary defect in need of subsequent reconstruction. Further study is needed to isolate a precise and treatment protocol that yields a predictable treatment course and outcome, as study reports varied based on frequency of applications and special considerations, such as the above-cited 2-cm margin past suspected lesion borders. In this patient’s case, applications were every other day.
The patient provided written consent for the use of her images.
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