Perineural invasion is strongly indicative of aggressive behavior and risk of metastases. True perineural invasion requires histologic finding of cancer invasion of the nerve or cancer invasion of the epineurium adjacent to the nerve. This must be distinguished from cancer near a nerve, cancer encompassing a nerve, and perineural inflammation.
Cancer cells within the nerve or attached to the nerve (epineurium) are clear examples of perineural invasion. This reflects cancer cells migrating via angioinvasion or through nerve lymphatics.
Cancer cells near the nerve or even encompassing a peripheral nerve branch do not represent the same behavior. In these cases, the nerve branch simply happens to be in the area of direct cancer spread. Dr. Matthew Goodman described this as perineural crowding. This does not represent the dreaded perineural invasion.
Perineural inflammation is often highlighted by Mohs dermatologists at the time of Mohs surgery. It is done to demonstrate difficulty in visualizing cancer cells within a sea of inflammatory infiltrate. Cancer cells can be missed in these settings thus requiring additional Mohs levels to confirm histologic clearance. Perineural inflammation by itself does not represent more aggressive cancer behavior.
Perineural invasion, given its association with lymphatic spread, places regional lymph nodes at risk for metastatic spread. Sentinel lymph node biopsy becomes a crucial diagnostic tool in assessing the lymph nodes.
Perineural invasion can also be associated with skip areas along the nerve. In such cases, resection of up to 5 cm segment of the nerve in question would be advisable. This nerve resection would serve therapeutic goals and as a diagnostic indicator. In the case of lower lip squamous cell cancer with perineural invasion, resection of the nerve proximal to the tumor would be considered – the mental and inferior alveolar nerves. Alternatively, radiation of the proximal path of the nerve could be entertained. However, when the nerve lies within the bone, such as the inferior alveolar nerve, delayed osteoradionecrosis of the mandible would be a concern.