ORIGINAL ARTICLE In vivo reflectance confocal microscopy to monitor the response of lentigo maligna to imiquimod Ivette Alarcon, MD, a,b Cristina Carrera, MD, a,b,c Llucia Alos, MD, d,e Josep Palou, MD, d Josep Malvehy, MD, PhD, a,b,c and Susana Puig, MD, PhD a,b,c,e Barcelona, Spain Background: Imiquimod has been used for treating lentigo maligna (LM) in selected cases when surgery is not an appropriate option because of functional or aesthetic impairment. Reflectance confocal microscopy (RCM) is a noninvasive method that has not been validated for monitoring the treatment of LM with imiquimod. Objective: We sought to evaluate the use of in vivo RCM to accurately monitor the response of LM to nonsurgical treatment with topical imiquimod. Methods: Twenty patients with confirmed facial LM, not amenable to surgical treatment or radiation therapy, were included prospectively. Clinical evaluation was performed by dermoscopy, RCM, and histopathology. Patients applied imiquimod 5% for 8 weeks. The affected area was assessed using the previously described LM score on RCM, and target sample biopsies were performed to confirm or discard RCM findings. Results: Fifteen of the 20 patients (75%) presented histologic tumor clearance. Confocal microscopy identified 70% of these responders with no false-negative results, and when compared with histopathology, there was no significant difference in evaluating the response to imiquimod. Limitations: The impossibility of examining the entire lesion by means of histopathology is a limitation. Conclusion: In vivo RCM evaluation was useful in accurately monitoring the response of LM to nonsurgical treatment with topical imiquimod in patients when surgery is contraindicated. ( J Am Acad Dermatol http:// dx.doi.org/10.1016/j.jaad.2014.02.043.) Key words: dermoscopy; imiquimod; lentigo maligna; melanoma; noninvasive diagnosis; nonsurgical treatment; reflectance confocal microscopy. L entigo maligna (LM) is an early form of melanoma with an incidence that has increased during the past 2 decades. 1 Clinically, it is a pigmented lesion that occurs on sun-exposed skin, particularly the head and neck areas, of elderly patients. 2,3 It accounts for 79% to 83% of all melanoma in situ tumors, ranking as the most prevalent subtype. 1 Untreated, LM is associated with a 5% to 50% risk of progressing to LM mela- noma, the invasive counterpart, which is also increasing in individuals older than 45 years. 3,4 For many years, surgical excision with 5-mm clinical margins was the mainstay for the treatment of LM, but this recommendation was based on a 1992 From the Dermatology a and Pathology d Departments, Melanoma Unit, Hospital Clinic of Barcelona; Institut de Recerca Biom edica August Pi i Sunyer (IDIBAPS) b ; Centro de Investigaci on Biom edica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII) c ; and Universitat de Barcelona. e The research at the Melanoma Unit in Barcelona is partially funded by grants 09/1393 and 12/00840 from Fondo de Investigaciones Sanitarias, Spain; by the Centro de Investigaci on Biom edica en Red (CIBER) de Enfermedades Raras of the Instituto de Salud Carlos III, Spain, cofunded by ‘‘Fondo Europeo de Desarrollo Regional, Uni on Europea, Una manera de hacer Europa’’; by the Ag encia de Gesti o d’Ajuts Universitaris i de Recerca (AGAUR) 2009 SGR 1337 of the Catalan Government, Spain; by the European Commission under the Sixth Framework Programme, Contract no. LSHC-CT-2006-018702 (GenoMEL); and by the National Cancer Institute of the US National Institutes of Health (CA83115). The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; or in the preparation, review, or approval of the manuscript. Conflicts of interest: None declared. Accepted for publication February 27, 2014. Reprint requests: Susana Puig, MD, PhD, Dermatology Department, Melanoma Unit, Hospital Clinic Barcelona, Villarroel 170, 08036 Barcelona, Spain. E-mail: susipuig@gmail.com. Published online April 8, 2014. 0190-9622/$36.00 Ó 2014 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2014.02.043 1