Perineural invasion in oral squamous cell carcinoma: a discussion of significance and review of the literature.

Perineural invasion (PNI) is a tropism of tumor cells for nerve bundles in the surrounding stroma. It is a form of tumor spread exhibited by neurotropic malignancies that correlates with aggressive behavior, disease recurrence and increased morbidity and mortality. Oral squamous cell carcinoma (OSCC) is a neurotropic malignancy that traditionally has been difficult to treat and manage. Evidence suggests that demonstration of PNI in OSCC should impact adjuvant treatment decisions and surgical management of this disease. Despite its importance as a prognostic indicator, experimental studies to explore the molecular mechanisms responsible for PNI are limited. The aim of this review is to discuss the difficulties in evaluating for PNI, review the literature regarding the relationship of PNI with patient outcomes in OSCC, and summarize the recent studies describing the molecular agents associated with this pathological phenomenon.