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Background: Optical coherence tomography combines principles of ultrasonography and optical interferometry to provide real-time cross-sectional images of subsurface microstructure of tissue in vivo. Objective: The purpose of this pilot study was to define and characterize basal cell carcinoma by using optical coherence tomography. Methods: Twenty-three patients with 49 lesions clinically suggestive of superficial basal cell carcinoma were recruited. Optical coherence tomography was used to characterize the features of the pearly papules in real time and in vivo. Shave biopsy and light microscopic images were compared with images from optical coherence tomography. Results: Basal cell carcinoma was identified in 27 patients; all 27 had optical coherence tomographic images for comparison. Seven images were uninterpretable, probably because of technical problems. Of the remainder, 20 sites matched the histologic features seen on light microscopy, with excellent correlation between optical coherence tomographic images and histopathologic features of superficial, nodular, micronodular and infiltrative basal cell carcinomas. Limitations: This study was limited by the small number of patients examined. Also, as this study was not designed as an intent-to-diagnose study, the actual predictive value of optical coherence tomography technology remains unproven. Conclusions: Optical coherence tomography technology has potential for the diagnosis and histopathologic characterization of basal cell cancer. Additional studies to determine any practical role for optical coherence tomography are indicated.