Diameter of involved nerves predicts outcomes in cutaneous squamous cell carcinoma with perineural invasion: an investigator-blinded retrospective cohort study

BACKGROUND Perineural invasion (PNI) has been associated with poor prognosis in cutaneous squamous cell carcinoma (CSCC), but it is unclear how different degrees of nerve involvement affect prognosis. OBJECTIVE To determine whether the diameter of nerves invaded by CSCC affects outcomes of recurrence, metastasis, and disease-specific and overall survival. METHODS A retrospective cohort study was conducted of patients with CSCC with PNI. Dermatopathologists blinded to subject outcomes determined the diameter of the largest involved nerve. RESULTS Data were obtainable for 48 patients. Small-caliber nerve invasion (SCNI) of nerves less than 0.1 mm in diameter was associated with significantly lower risks of all outcomes of interest. Disease-specific death was 0% in subjects with SCNI, versus 32% in those with large-caliber nerve invasion (LCNI) (p=.003). Other factors associated with significantly worse survival were recurrent or poorly differentiated tumors or tumor diameter of 2 cm or greater or depth of 1 cm or greater. On multivariate analysis, only tumor diameter and age predicted survival. CONCLUSIONS The individual prognostic significance of factors associated with poor survival remains uncertain. Small-caliber nerve invasion may not adversely affect outcomes. Defining PNI as tumor cells within the nerve sheath and routine recording of diameter of involved nerves, tumor depth, and histologic differentiation on pathology reports will facilitate further study.