REVIEW Through the looking glass: Basics and principles of reflectance confocal microscopy Syril Keena T. Que, MD, a Naiara Fraga-Braghiroli, MD, b Jane M. Grant-Kels, MD, a Harold S. Rabinovitz, MD, b Margaret Oliviero, ARNP, MSN, b and Alon Scope, MD c,d Farmington, Connecticut; Miami, Florida; Tel Aviv, Israel; and New York, New York Reflectance confocal microscopy (RCM) offers high-resolution, noninvasive skin imaging and can help avoid obtaining unnecessary biopsy specimens. It can also increase efficiency in the surgical setting by helping to delineate tumor margins. Diagnostic criteria and several RCM algorithms have been published for the differentiation of benign and malignant neoplasms. We provide an overview of the basic principles of RCM, characteristic RCM features of normal skin and cutaneous neoplasms, and the limitations and future directions of RCM. ( J Am Acad Dermatol http://dx.doi.org/10.1016/j.jaad.2015.04.047.) Key words: basal cell carcinoma; cutaneous oncology; melanoma; noninvasive imaging; reflectance confocal microscopy; squamous cell carcinoma; tumors/neoplasm. I n this rapidly developing medical/technological era, noninvasive imaging devices have emerged as useful tools for diagnosing cutaneous neoplasms. Reflectance confocal microscopy (RCM) provides high-resolution, noninvasive imaging and can be used as an adjunct to the management of skin cancers. Herein, we describe for the general dermatologist the basic principles of RCM, detail its potential applications and current limitations, and discuss RCM features of both normal skin and cutaneous neoplasms. FUNDAMENTALS OF REFLECTANCE CONFOCAL MICROSCOPY In vivo RCM is a noninvasive optical imaging technique that provides high-resolution images of skin. RCM relies on a low-power laser that emits near-infrared light (830 nm). To attain a lateral resolution of about 1 m, RCM allows only light back-reflected from a desired focal point within the skin to pass back through a gating pinhole and enter the detector. The basic RCM optical section image is comparable to high magnification histopathology at about 330; the advantage of RCM compared to histopathology is that optical sections can be obtained in vivo, with no disruption of the skin. Output images are horizontal and parallel to the surface of the skin, visually sectioned in a manner resembling histopathologic specimens in Mohs micrographic surgery. 1 RCM can image the epidermis and papillary dermis but is limited to an imaging depth of about 200 m. The wide-probe RCM (VivaScope 1500; CaliberID, Rochester, NY) stitches optical sections into larger mosaic images, allowing a field of view of 8 3 8 mm. The recent introduction of the handheld RCM (VivaScope 3000; CaliberID) has enabled imaging of lesions on concave surfaces, which are typically difficult to image using the bulky From the Departments of Dermatology at the University of Connecticut Health Center, a Farmington, University of Miami Miller School of Medicine, b Miami, and Sheba Medical Center and Sackler Faculty of Medicine, c Tel Aviv University; and the Dermatology Service, d Memorial Sloan Kettering Cancer Center, New York. Supported by the European Commission Marie Curie FP7 Reintegration Grant to Dr Scope (PIRG07-GA-2010-268359). Dr Rabinovitz has received equipment and funding for a fellowship program from Lucid Inc. Dr Rabinovitz is an investigator in a study coordinated by Lucid Inc, manufacturer of a commercial confocal microscope. The other authors have no conflicts of interest to declare. Accepted for publication April 23, 2015. Correspondence to: Syril Keena T. Que, MD, University of Connecticut Health Center, Department of Dermatology, 21 South Rd, Farmington, CT 06032. E-mail: keenaq@gmail.com. Published online June 4, 2015. 0190-9622/$36.00 Ó 2015 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2015.04.047 Abbreviations used: BCC: basal cell carcinoma DEJ: dermoepidermal junction RCM: reflectance confocal microscopy SCC: squamous cell carcinoma 1