Perineural Involvement: What Does it Mean?

Perineural invasion is an important mechanism for local spread in certain malignant cutaneous neoplasms and is associated with aggressive tumor growth, increased frequency of recurrence, and increased morbidity and mortality. Thus, perineural invasion is often used both as a marker of malignancy and an indicator of aggressive behavior. There exists, however, a limited number of cutaneous and noncutaneous benign neoplasms in addition to reactive lesions that either demonstrates perineural involvement or mimics it. Given the association of the term "invasion" with malignant neoplasms, we use the term "perineural involvement" to describe neoplastic cells of any type infiltrating within nerves. Despite the presence of perineural involvement in these benign lesions, there is no evidence of aggressive behavior compared with similar examples which do not demonstrate perineural involvement. The aim of this article is to review cutaneous and noncutaneous benign neoplasms and reactive conditions that may demonstrate or mimic perineural involvement. Recognition of the spectrum of benign processes that may resemble perineural involvement may help prevent diagnostic confusion, misdiagnosis, and overly aggressive treatment.