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Background: Diagnosis of pigmented and non pigmented lesions involving the oral mucosa are complicated because of limited access to the oral cavity with tools like dermoscopy or other methods usually applied for the evaluation of lesions involving skin and outer part of the oral cavity as lips and external cheeks. Confocal microscopy has been demonstrated to have a singnificant impact in the diangosis of skin and genital lesions. Adapted tools are needed in order to covoer the umeet needs in those type of clinical setting. Methods: A new designed confocal microsocpy optic for the access to the in part fo the oral caviy has been desingned and realized by the ingeniers from Memorial Sloan Kettern Cancer Center of New York and initially tested on a series of 80 patients affected by oral cancer testing histopathology/confocal microscopy blinded agreement. Moreover, 110 different oral lesions of different type have been classified accordingly to the lesion colour (white, red and brouwn/black), convering a large spectrum of entities moving from inflammatory, pre-cancer and oral melanocitic and non melanocytic cancer, has been studied with the new confocal optic. A video mapping has been beveloped staring from confocal microscopy videos in order to provide wide mosaics of confocal microscopy images for large confocal field of view of the lesions Results: The new designed confocal optic lets the evaluation of lesions involving also the inner part of the oral cavity. Comparison between confocal microscopy and histoloy demonstrated high agreement between blinded readers (95% for normal tissue and 81.7% for tumors), high specificity (98.3%) and negative predictive values (96.6%) for normal tissue identification, and high sensitivity (90%) and positive predictive values (88.2%) for tumor detection. Impact of video mapping in the interpretation of cinfical analysis of the tissue has been also demonstrated. A simplified approach to the different oral lesions subtypes has been considered and tested on the large series of cases demonstrating the usefulness of a systematic approach to oral lesions. Conclusions: The new designed confocal microscopy optic for oral mucosa represents a promising tool for the evaluation of the different mucosal lesions, moving from inflammatory conditons to oral cancer, affecting the inner part of the oral cavity. Diagnosis, clinical and therapeutic follow-up and lesions mapping can be done with confocal microscopy also in this difficult anatomical areas