HISTOBLOC Study Protocol — Intraoperative Confocal Microscopy for Surgical Margin Assessment Compared With Conventional Frozen Section. (Preprint)

BACKGROUND Accurate assessment of surgical margins is essential in the treatment of squamous cell carcinoma (SCC) of the upper aerodigestive tract or cutaneous origin, as well as basal cell carcinoma (BCC). Intraoperative frozen-section analysis is the current standard but is time-consuming and requires coordination among surgical and pathology teams. Reflectance confocal microscopy offers rapid, real-time evaluation of surgical margins and may provide diagnostic information comparable to frozen-section analysis, while enabling the development of a reference atlas for tumor visualization. OBJECTIVE The HISTOBLOC study aims to evaluate the concordance between confocal microscopy and intraoperative frozen-section examination for assessing surgical margins in SCC and BCC. A secondary objective is to compile a confocal imaging reference atlas to document tumor features and support consistent interpretation METHODS HISTOBLOC is a prospective, monocentric, randomized pilot study conducted at the Institut de Cancérologie de Lorraine, a nonprofit comprehensive cancer institute. Patients undergoing surgical excision for SCC or BCC have their margins assessed using both confocal microscopy and frozen-section analysis. The study measure concordance between the two methods and the time required for intraoperative margin assessment. RESULTS Patient recruitment for the study began on July 26, 2023, and was completed in June 4, 2025. All patients were enrolled according to the approved study protocol. Experimental procedures have been conducted in all recruited participants, and data collection has been completed. The results are currently undergoing statistical analysis and interpretation. CONCLUSIONS This protocol describes a study designed to determine whether confocal microscopy can provide rapid, reliable intraoperative margin assessment comparable to frozen-section analysis, and to generate a reference atlas for clinical and research use. CLINICALTRIAL ClinicalTrials.gov; NCT05935995; https://clinicaltrials.gov/study/NCT05935995