Evaluation of nerves in Mohs micrographic surgery: Histologic mimickers of perineural invasion and nervous tissue on frozen section

Background Perineural invasion (PNI) is an important histologic finding and may be a negative prognostic factor for squamous cell carcinoma (SCC). It may be associated with more-aggressive tumor behavior. Mohs surgeons encounter microscopic PNI regularly and must be able to diagnose it accurately to guide care decisions. Objective To describe benign histologic mimickers of PNI and neural structures in SCC commonly encountered on frozen, hematoxylin and eosin-stained sections and to review how to differentiate them from PNI. Methods and Materials Review of the literature regarding histologic mimickers of PNI and additional contributions to frozen section PNI and nerve tissue mimickers. Results We describe benign findings, including arrector pili muscles, eccrine muscles, vessels, granulomatous inflammation, and eddies of SCC, that may each be mistaken for nerves or PNI. We discuss the ways in which they may be distinguished on frozen sections and review other commonly encountered entities that resemble PNI. Conclusion Perineural inflammation and peritumoral fibrosis are common mimickers of PNI on frozen section, although other mimickers exist on permanent sections. Normal structures may appear "neural" by way of frozen tissue orientation, processing, or inflammation and thus must be differentiated from nerve tissue and PNI during Mohs surgery.