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Johannes J. Fagan, FCS(SA), MMed(Otol); Bobby Collins, MD; Leon Barnes, MD; Frank D'Amico, PhD; Eugene N. Myers, MD; Jonas T. Johnson, MD

Arch Otolaryngol Head Neck Surg. 1998;124:637-640.

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.

From the Departments of Otolaryngology (Drs Fagan, Myers, and Johnson) and Pathology (Drs Collins and Barnes), University of Pittsburgh School of Medicine, and the Data Analysis Institute, Dusquesne University (Dr D'Amico), Pittsburgh, Pa.

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