High-Resolution Microendoscopy Shows Promise for Intraoperative Head and Neck Squamous Cell Carcinoma Margin Detection

How viable is high-resolution microendoscopy (HRME) in providing intraoperative margin detection for head and neck squamous cell carcinoma (HNSCC)?

Background: Appropriate oncologic surgical margins are difficult to achieve, most notably due to the inability to see individual cancer cells during surgery and the heterogeneity in the biologic behavior of malignant cells. Currently, most surgeons rely on intraoperative frozen section margin analysis, but negative surgical margins may not equate to malignant disease eradication. HRME as an optical biopsy may allow for real-time decision making during oncologic resection.

Study design: Single institution, prospective, feasibility trial (phase I) of in vivo optical imaging of 33 adult patients with squamous cell carcinoma of the upper aerodigestive tract.

Setting: Department of Otolaryngology–Head and Neck Surgery, Division of Head and Neck Oncology, Icahn School of Medicine at Mount Sinai, New York.

Synopsis: Images from 98 unique sites passed the quality control review and were used for further analysis. The HRME images of normal squamous epithelium show small, bright nuclei with dark cytoplasm and relatively large and evenly spaced internuclear separation. Images from invasive carcinoma show high nuclear-to-cytoplasmic ratio and a distinct loss of cellular organization, with haphazard, unevenly spaced, and abnormally large nuclei. In addition, a transition zone often could be observed at the interface of the tumor and adjacent benign mucosa. Statistical analysis revealed that the mean accuracy in correctly diagnosing neoplastic or benign mucosa was 95.1%. The mean sensitivity and specificity were 96% and 95%, respectively. The negative predictive value was 98%, while the positive predictive value was 91%. The Fleiss kappa statistic for interrater reliability was 0.81, with a standard error of 0.014 and a 95% confidence interval. Limitations generally revolved around technology issues: Severe inflammation, keratin debris, bleeding, and artifacts during imaging will impair the ability of optical devices to obtain accurate, interpretable images, and HRME technology is currently limited to surface imaging.

Bottom line: Despite several technical limitations, HRME shows promise as a technique for intraoperative margin control and a platform for molecular imaging technologies.

Citation: Miles BA, Patsias A, Quang T, Polydorides AD, Richards-Kortum R, Sikora AG. Operative margin control with high-resolution optical microendoscopy for head and neck squamous cell carcinoma. Laryngoscope. 2015;125:2308-2316.