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Am J Otolaryngol. 2012 Mar-Apr;33(2):212-5. doi: 10.1016/j.amjoto.2011.06.003. Epub 2011 Dec 15.

A novel classification system for perineural invasion in noncutaneous head and neck squamous cell carcinoma: histologic subcategories and patient outcomes.

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  • 1University of California-Los Angeles Medical Center, Los Angeles, CA, USA.



The aims of this study were to define a novel classification system of tumor perineural invasion (PNI) with respect to tumor/nerve involvement such as intratumoral (IT), peripheral, or extratumoral (ET) and to determine the prognostic significance of each of these histologic subcategories in patients with noncutaneous head and neck squamous cell carcinoma (HNSCC).


This study is a retrospective chart review and histologic analysis of patients with HNSCC in the setting of a tertiary care medical center.


A clinical chart review of 142 patients with HNSCC who underwent primary surgical treatment from January 2004 through December 2007 was performed. Clinical information collected included patient age, sex, alcohol and tobacco use, tumor location, TNM stage, postoperative adjuvant chemotherapy and/or radiation treatment, and patient outcome. For each case, PNI density, the distance of each PNI focus to the tumor edge, and size of the largest nerve involved were measured. Furthermore, PNI was subcategorized as IT, peripheral, or ET. A Cox regression analysis was performed to determine if PNI was related to regional disease recurrence. Kaplan-Meier survival analysis was also performed.


Among the 142 patients, 37 (26%) had disease progression. The maximum extent of PNI was significantly correlated with disease-free survival on multivariate analysis (P = .019) and was also significantly related to disease-free survival when T stage (P = .017), N stage (P = .021), and T and N stages (P = .02) were added to the Cox regression model. Kaplan-Meier analysis demonstrated a trend toward increased disease-free survival of PNI negative and IT/peripheral PNI compared with ET PNI.


Perineural invasion is correlated with nodal status and T stage and is related to disease-free survival. It can be subcategorized as IT, peripheral, or ET. This novel classification system has important implications with regard to clinical outcome and may help define a cohort of patients that may require more aggressive management.

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