Beyond Frozen Section: Evolving Methodologies for Intraoperative Assessment of Surgical Margins in Breast Conservation Surgery

Intraoperative margin evaluation is very important in the management of breast cancer patients, specifically in breast conserving therapy in which attaining negative margins is a prerequisite. Microscopic involvement of margins shows two to three times increase in local recurrence. Frozen section is mostly employed for intraoperative assessment of margins. It has, however, the inherent limitations of being expensive, more time-consuming, with difficult serial sectioning, associated technical issues regarding adipose tissue freezing and tissue consumption during the procedure that could leave limited tissue for the permanent sections, thus compromising the final diagnosis, in addition to its intrinsic procedural standardization deficits. A variety of other techniques and methodologies have been developed that can complement frozen section or be employed independently for increased diagnostic efficacy and accuracy like intraoperative touch preparation cytology, assessment by margin probes, flow cytometry, optical coherence tomography (OCT), integrated OCT with microscopy or with dye-enhanced field polarization, polarization-sensitive multimodal imaging, and nonlinear microscopy. This review article states what defines free margins, highlights the different histological options for margin evaluation, and reflects on the evolving methodologies to diagnose the margins intraoperatively.