Perineural Invasion and Its Interrelationship with Neural Repair: A Review

The impact of perineural invasion and perineural spread on survival and the MR imaging of this tumor spread have been well documented in the literature. What has not been addressed in the radiology literature is the mechanics that are behind perineural invasion. Perineural invasion is not the result of a passive invasion of a nerve by tumor, a common misconception. Because there are no lymphatics within a nerve, perineural invasion is not mediated by a direct lymphatic extension. Rather, perineural invasion is the result of complex molecular interactions between a nerve and an adjacent cancer. Once the cancer has entered a nerve, it can travel in the spaces between fascicles, which explains how such perineural invasion can appear at great distances from the primary tumor. This article reviews the current concepts regarding the mechanisms of perineural invasion and the relationship to peripheral nerve regeneration. Perineural invasion is diagnosed by histology, whereas perineural spread can be identified on imaging.Learning Objective: The reader will learn the intimate relationship between a tumor and its adjacent nerves that lead to perineural invasion. This process is the result of a series of molecular pathways, in part related to nerve regeneration.