ORIGINAL ARTICLE 5% Imiquimod Cream and Reflectance-Mode Confocal Microscopy as Adjunct Modalities to Mohs Micrographic Surgery for Treatment of Basal Cell Carcinoma ABEL T ORRES , MD, JD, n AGNIESZKA NIEMEYER, MD, n B EATRICE B ERKES , MD, n DIEGO MARRA, MD, CARL S CHANBACHER, MD, w S ALVADOR GONZA ´ LEZ, MD z MARY OWENS , MD, § AND B LAINE MORGAN, MS § n Loma Linda University Medical Center, Dermatology Office, Faculty Medical Offices, Loma Linda, California; w Dana Farber Cancer Institute, Boston, Massachusetts; z Wellman Laboratories of Photomedicine, Dermatology Department, Harvard Medical School, Boston, Massachusetts; and § 3M Pharmaceuticals, St. Paul, Minnesota BACKGROUND. Imiquimod is an immune response modifier that up-regulates cytokines and has been shown in clinical studies to reduce or clear basal cell carcinoma tumors when applied topically. OBJECTIVE. The objectives were to evaluate the efficacy of 5% imiquimod cream in treating basal cell carcinoma preceding excision by Mohs micrographic surgery and to determine if re- flectance-mode confocal microscopy is useful to establish the need for surgical intervention after imiquimod treatment. METHODS. Subjects applied study cream to one biopsy-con- firmed basal cell carcinoma tumor 5/week for 2, 4, or 6 weeks in this vehicle-controlled, double-blind study. Confocal micros- copy was used for the 6-week treatment group to examine the target tumor area at each interval visit and immediately before Mohs micrographic surgery. After the Mohs micrographic sur- gery excision, the tissue was evaluated histologically, and the excision area was measured. Confocal microscopy readings were correlated to the histologic diagnosis. RESULTS. Tumors cleared or the target tumor area was reduced in subjects in the 4- and 6-week dosing regimens. Confocal microscopy assessments correlated well with the histologic diagnosis. CONCLUSION. Imiquimod improved excision results relative to vehicle when used for treating basal cell carcinoma before Mohs micrographic surgery. Confocal microscopy assessments corre- lated well with tumor response to therapy, suggesting that con- focal microscopy may help determine the need for surgery. THIS STUDY WAS FUNDED BY A GRANT FROM 3M PHARMACEUTICALS (ST. PAUL, MN), AND THE CONFOCAL MICROSCOPE AND SUPPLIES FOR MICROSCOPY WERE SUPPLIED BY LUCID, INC. (HENRIETTA, NY). MOHS MICROGRAPHIC surgery is one of the most definitive excision options for basal cell carcinoma. 1 Mohs micrographic surgery involves excision of the clinically evident neoplastic lesion, microscopic anal- ysis of frozen tumor sections with meticulous mapping of the skin and the excised tissue, and reexcision of histologically identified residual neoplasm until tumor- free margins are obtained. Using Mohs micrographic surgery allows selective excision of basal cell carcino- ma, thereby sparing healthy tissue. Because tumors frequently extend beyond their visible borders, or show dramatic subclinical extension, however, the re- sulting surgical defect following Mohs micrographic surgery can be significantly larger than the clinically apparent lesion and may compromise the final cos- metic outcome. 2–4 The immune response modifier, imiquimod, is ap- proved for the treatment of external genital warts and actinic keratosis and has been shown in several studies to be beneficial for the clearance of both nodular and superficial (basal cell carcinoma) lesions and was recently approved for the treatment of superficial BCC. 5–8 Imiquimod induces interferon and other cytokines locally when applied topically to the tumor site, producing an antitumor effect. 9 Imiquimod could be used to reduce the size and the subclinical tumor extensions of primary basal cell carcinoma lesions pri- or to Mohs micrographic surgery, thereby decreasing the resultant surgical defects and the degree of cos- metic damage caused by Mohs micrographic surgery. In using a noninvasive therapy such as imiquimod to reduce the size of a basal cell carcinoma lesion, it is important to be confident of the treatment outcome so that the area excised after treatment actually has tumor present or that the area spared is clear of tumor. Confocal microscopy has been effectively used to char- acterize basal cell carcinoma and as an adjunct to sur- r 2004 by the American Society for Dermatologic Surgery, Inc.  Published by Blackwell Publishing, Inc. ISSN: 1076-0512/04/$15.00/0  Dermatol Surg 2004;30:1462–1469 Address correspondence and reprint requests to: Abel Torres, MD, JD, Loma Linda University Medical Center, Dermatology Office, Faculty Medical Offices, 11370 Anderson Street, Suite 2600, Loma Linda, CA 92354, or e-mail: ABELT@aol.com.