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The limited sampling of biopsy and histopathology can lead to incomplete and/or inaccurate assessment of basal cell carcinomas (BCCs), subtypes and depth, which can affect diagnosis and treatment outcome. Reflectance confocal microscopy (RCM) combined with optical coherence tomography (OCT) can help achieve comprehensive 3-dimensional sampling in vivo, which may improve the diagnostic accuracy and margin assessment of BCCs. In a clinical study, we tested a combined RCM-OCT probe on 85 patients, with either clinically-suspicious (n=60, in intact skin) or biopsy-proven BCCs (n=25, in scarred skin). We correlated BCC features in RCM and OCT images with histopathology, calculated diagnostic accuracy and correlated depth predicted by OCT with histopathologically measured depth. The main features were small tumors extending from the basal cell layer at the dermal-epidermal junction; small and large tumor nests; in dermis; dark silhouettes; dilated blood vessels; horn cyst and bright peritumoral stroma. Deeper features such as necrosis and intratumoral mucin pools were correlated on OCT and histology. Higher sensitivity and negative predictive value (100%) and comparable specificity (48% vs 56% on RCM) and positive predictive value (82.19 vs 84.59 % on RCM) were observed for the combined RCM-OCT device for diagnosis of all lesions (n=85). Relatively higher specificity (94.1%) and positive predictive value (75%) were observed in the clinically suspicious lesions (n=60, in intact skin). High correlation was observed (R=0.86) between the OCT predicted depth and histopathologically measured depth. Therefore, RCM-OCT imaging may be prospectively used to comprehensively diagnose suspicious BCC lesions, determine subtype and triage for treatment.
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