There has been extensive research regarding the use of RCM in the evaluation of cutaneous neoplasms and other skin diseases. Numerous features and patterns have been identified and described that correspond with different skin diseases and correspond well with histopathology (Figure 2).13,16,17 Reflectance confocal microscopy has demonstrated consistently high accuracy in the diagnosis of melanocytic lesions, with a sensitivity of 93% to 100% and a specificity of 75% to 99%.18-21 Reflectance confocal microscopy is especially useful in the evaluation of clinically or dermoscopically equivocal pigmented lesions due to greater specificity, resulting in a reduction of unnecessary biopsies.22,23 It also has high accuracy in the diagnosis of keratinocytic neoplasms, with a sensitivity of 82% to 100% and a specificity of 78% to 97% in the diagnosis of BCC,24 and a sensitivity of 74% to 100% and specificity of 78% to 100% in the diagnosis of squamous cell carcinoma (SCC).25,26 Evaluation of SCC and actinic keratosis (AK) using RCM may be limited by considerable hyperkeratosis and ulceration. In addition, it can be challenging to differentiate AK and SCC on RCM, and considerable expertise is required to accurately grade cytologic and architectural atypia.27 However, RCM has been used to discriminate between in situ and invasive proliferations.28 Reflectance confocal microscopy has wide applications in the diagnosis and management of cutaneous infections29,30 and inflammatory skin diseases.29,31-33 Recent RCM research explored the use of RCM to identify biopsy sites,34 delineate presurgical tumor margins,35,36 and monitor response to noninvasive treatments.37,38
Figure 2. A, Nonpolarized contact dermoscopy of a suspicious lesion showed prominent vessels, irregular pigmentation, and prominent follicular openings, which are not classic features of basal cell carcinoma. B, A reflectance confocal microscopy mosaic of the same lesion showed well-defined tumor nodules, resulting in a diagnosis of basal cell carcinoma.
Optical Coherence Tomography
Optical coherence tomography is an imaging modality that utilizes light backscatter from infrared light to produce grayscale cross-sectional or vertical images and horizontal en face images.39 Optical coherence tomography can visualize structures in the epidermis, dermoepidermal junction, and upper dermis.40 It can image boundaries of structures but cannot visualize individual cells.
There are different types of OCT devices available, including frequency-domain OCT (FD-OCT), or conventional OCT, and high-definition OCT (HD-OCT). With FD-OCT, images are captured at a maximum depth of 1 to 2 mm but with limited resolution. High-definition OCT has superior resolution compared to FD-OCT but is restricted to a shallower depth of 750 μm.39 The main advantage of OCT is the ability to noninvasively image live tissue and visualize 2- to 5-times greater depth as compared to RCM. Several OCT devices have obtained US Food and Drug Administration approval; however, OCT has not been widely adopted into clinical practice and is available only in tertiary academic centers. Additionally, OCT imaging in dermatology is rarely reimbursed. Other limitations of OCT include poor resolution of images, high cost to procure an OCT device, and the need for advanced training and experience to accurately interpret images.40,41
Optical coherence tomography primarily is used to diagnose cutaneous neoplasms. The best evidence of the diagnostic accuracy of OCT is in the setting of BCC, with a recent systematic review reporting a sensitivity of 66% to 96% and a specificity of 75% to 86% for conventional FD-OCT.42 The use of FD-OCT results in an increase in specificity without a significant change in sensitivity when compared to dermoscopy in the diagnosis of BCC.43 Melanoma is difficult to diagnose via FD-OCT, as the visualization of architectural features often is limited by poor resolution.44 A study of HD-OCT in the diagnosis of melanoma with a limited sample size reported a sensitivity of 74% to 80% and a specificity of 92% to 93%.45 Similarly, a study of HD-OCT used in the diagnosis of AK and SCC revealed a sensitivity and specificity of 81.6% and 92.6%, respectively, for AK and 93.8% and 98.9%, respectively, for SCC.46
Numerous algorithms and scoring systems have been developed to further explore the utility of OCT in the diagnosis of cutaneous neoplasms.47,48 Recent research investigated the utility of dynamic OCT, which can evaluate microvasculature in the diagnosis of cutaneous neoplasms (Figure 3)49; the combination of OCT with other imaging modalities50,51; the use of OCT to delineate presurgical margins52,53; and the role of OCT in the diagnosis and monitoring of inflammatory and infectious skin diseases.54,55
Figure 3. A, A nonpolarized contact dermoscopy image of a nodular pigmented basal cell carcinoma showed large blue-gray ovoid nests, arborizing vessels, and small fine telangiectases. B, A microvascular en face dynamic optical coherence tomography image (size, 6×6 mm; depth, 300 µm) of the same lesion revealed circumscribed areas (asterisks) and branching/arborizing vessels (arrows). C, A cross-sectional optical coherence tomography image of the same lesion showed ovoid structures (asterisks) corresponding with tumor nests with dark peripheral borders and thinning of the epidermis above them.
Final Thoughts
In recent years, there has been a surge of interest in noninvasive techniques for diagnosis and management of skin diseases; however, noninvasive tools exist on a spectrum in dermatology. Dermoscopy provides low-cost imaging of the skin’s surface and has been widely adopted by dermatologists and other providers to aid in clinical diagnosis. Reflectance confocal microscopy provides reimbursable in vivo imaging of live tissue with cellular-level resolution but is limited by depth, cost, and need for advanced training; thus, RCM has only been adopted in some clinical practices. Optical coherence tomography offers in vivo imaging of live tissue with substantial depth but poor resolution, high cost, need for advanced training, and rare reimbursement for providers. Future directions include combination of complementary imaging modalities, increased clinical practice integration, and education and reimbursement for providers.