LAUSR

Dear Editor, Lentigo maligna (LM) is an in situ melanoma occurring in the sunexposed skin of elderly patients. It is characterized by an inhomogeneous-pigmented macula that grows slowly over few years or decades. The main challenges associated with treating LM include its location on the face and that it is poorly defined with a high risk of local recurrence. Moreover, if left untreated, at least 5% of LMs progress to an invasive melanoma called lentigo maligna melanoma, which may lead to a fatal metastatic disease. The first-line treatment for LM is surgical excision with a minimum excision margin of 5 mm, but this approach is not always feasible. LM often spreads subclinically and laterally, making surgical treatment challenging, especially in the periocular region. Obtaining adequate surgical margins in this area may present functional and esthetic reconstructive difficulties. Imiquimod, an immune-response modifier that acts as a toll-like receptor-7/8 agonist, stimulates the innate cutaneous immunity and the cellular arm of the adaptive immune response. It can be used offlabel as treatment of melanoma in situ, especially LM, and melanoma metastases. Combination of imiquimod with cryosurgery as a double topical treatment has been described as a nonsurgical alternative for LM, demonstrating good oncological, functional, and esthetic results. This combination may enhance immune function when compared with the application of each treatment alone. However, this combination may cause significant morbidity in anatomic locations such as the eyelids. Severe local reactions including redness, vesicles, erosions, ulcerations, crusting, swelling, discomfort, and pain, as well as conjunctivitis, ocular stinging, and keratitis have been reported. Most of these reactions are secondary to regular cryosurgery with liquid nitrogen. Liquid nitrogen achieves very low surface temperatures up to −196 C, and it should be used under a clinician's supervision to avoid unnecessary skin damage. To minimize severe local reactions, we used an ophthalmic cryosurgery system to increase the accuracy of contact cryosurgery (Figure 1). This system uses nitrous oxide, which freezes at −89 C, and it is commonly used in cataract and retinal surgeries. There is a substantial difference in the freezing temperature that it is capable of reaching. Nitrous oxide is applied by a probe with small metal cylinders through which the cryogen circulates (Video S1). Its freezing temperature is not as intense as that of liquid nitrogen, thus minimizing adverse effects, and inducing an over-additive therapeutic effect to that of imiquimod. Previously, a local anesthetic was administered to avoid pain sensation. Our treatment strategy involves a single cryosurgery session using a triple freeze–thaw cycle over the LM with a 1 cm margin, and then imiquimod administration 5 days a week for 8 weeks. To date, we have treated two patients with this technique who had rejected surgery. In both cases, treatment alternatives as well as long-term outcomes and the off-label nature of the combination therapy with immunocryosurgery were openly discussed with the patients and their relatives/legal custodians. The first case was of an irregular and heterogeneous brown-black macule, 22 × 15 mm in diameter, located on the right lower eyelid and affecting the lid margin in an 83-year-old female (Figure 2A). It had been growing gradually over the last 18 months. The biopsy revealed a diagnosis of LM. After 2 months of immunocryosurgery therapy, the LM cleared clinically. After 1 year of follow-up, a biopsy of a suspicious, slightly pigmented area on the lid margin was performed