Perineural invasion in squamous cell carcinoma of the head and neck

Objective: To determine if perineural invasion (PNI) of small nerves affects the outcome of patients with squamous cell carcinoma (SCC) of the upper aerodigestive tract. Design: Retrospective clinicopathological study of patients with at least 2 years of follow-up and with negative margins and no prior, synchronous, or metachronous SCC. Setting: Academic otolaryngology department. Patients: One hundred forty-two patients who had SCC of the oral cavity, oropharynx and hypopharynx, or larynx resected between 1981 and 1991. Intervention: Surgery with or without adjuvant therapy. Main Outcome Measures: Local recurrence was examined with respect to PNI, nerve diameter, and microvascular or microlymphatic invasion. Perineural invasion was correlated with lymph node metastasis, extracapsular spread, and survival. Results: :Perineural invasion of nerves less than 1 mm in diameter was present in 74 patients, lymphatic invasion in 53, and vascular invasion in 9. Perineural invasion was significantly associated with local recurrence (23% for PNI vs 9% for no PNI; P = .02), and disease-specific mortality (54% mortality for PNI vs 25% for no PNI; P < .001). With extralaryngeal tumors, PNI was associated with nodal metastasis (73% vs 46%; P = .03). Perineural invasion was not associated with extracapsular spread (P = .47). Microvascular invasion, lymphatic invasion, and nerve diameter were not significantly related to local recurrence. Conclusions: Perineural invasion of small nerves is associated with an increased risk of local recurrence and cervical metastasis and is, independent of extracapsular spread, a predictor of survival for patients with SCC of the upper aerodigestive tract.