A prospective evaluation of the clinical, histologic, and therapeutic variables associated with incidental perineural invasion in cutaneous squamous cell carcinoma

Background The prognosis and management of incidental perineural invasion (PNI) in patients with cutaneous squamous cell carcinoma (CSCC) has not been well defined. Objective We sought to investigate the clinical, histologic, and treatment characteristics associated with incidental PNI, histologic PNI extending beyond the tumor bulk, in patients with CSCC. Methods We conducted a multicenter prospective analysis of patients with CSCC undergoing Mohs micrographic surgery. Results The incidence of PNI was 4.6% in 753 CSCC cases. PNI was significantly associated with tumors of the head and neck ( P = .039), larger tumor diameter ( P < .001), presence of clinically palpable lymphadenopathy ( P = .012), and recurrent ( P < .001) and painful ( P < .001) tumors. Further, PNI was significantly associated with poor tumor differentiation ( P < .001), greater tumor thickness ( P < .001), a greater number of Mohs stages ( P < .001), and larger estimated maximum Mohs margin ( P < .001) required to clear the tumor. Limitations The low numbers of patients demonstrating incidental PNI limits this study. Conclusions The association of incidental PNI with clinicopathological indicators of poor prognosis suggests that incidental PNI may serve as a marker to improve the precision in the prognostic assessment of patients with CSCC.