Redefining Perineural Invasion in Head and Neck Cutaneous Squamous Cell Carcinoma

Otolaryngol Head Neck Surg. 2022 Oct;167(4):705-715. doi: 10.1177/01945998221076110. Epub 2022 Feb 8.


Objective: Perineural invasion (PNI) negatively affects disease-specific survival in patients with head and neck cutaneous squamous cell carcinoma (HNcSCC). We aim to analyze the prognostic implications of PNI-related features.

Study design: Retrospective cohort study.

Setting: Academic tertiary care hospital.

Methods: Retrospective chart review was performed on 104 patients diagnosed with HNcSCC between January 2011 and October 2019 who underwent resection, parotidectomy, and neck dissection with more than 1 year of follow-up. PNI was classified as incidental (identified on histopathology alone) or clinical (present on radiography and/or physical exam). Primary outcome measures were overall survival and disease-free survival (DFS). Kaplan-Meier analysis, logistic regression, and Cox regression were performed.

Results: The overall 5-year DFS was 57.9%. Sixty-one patients had PNI. On histopathology, 28 lesions showed complete nerve encirclement, 10 involved >5 nerves, and 12 involved named nerves. Patients with facial weakness (P = .026) and positive margins (P = .0029) had a higher likelihood of histopathologic PNI, and positive margins retained significance on multivariable analysis (P = .0079). Worse DFS was seen in patients with PNI (P = .004), advanced tumor stage (P = .049), positive margins (P = .014), and >5 nerves involved (P = .0061). Furthermore, histopathologic PNI was a predictor of DFS (hazard ratio [HR], 3.07; 95% CI, 0.33-1.38; P = .0061) overall and in the clinical PNI cohort (HR, 3.43; 95% CI, 1.65-7.10; P = .00091).

Conclusion: DFS was significantly worse in patients with PNI, facial nerve weakness, advanced T stage, positive margins, and multiple nerve involvement. Further characterization of PNI features may help improve prognostic predictions and identify patients who may benefit from more aggressive treatment.

Keywords: PNI; clinical PNI; cutaneous squamous cell carcinoma; head and neck cancer; incidental PNI; perineural invasion; survival.

MeSH terms

  • Carcinoma, Squamous Cell* / pathology
  • Head and Neck Neoplasms* / pathology
  • Head and Neck Neoplasms* / surgery
  • Humans
  • Margins of Excision
  • Neoplasm Invasiveness / pathology
  • Peripheral Nerves / pathology
  • Prognosis
  • Retrospective Studies
  • Skin Neoplasms* / pathology
  • Squamous Cell Carcinoma of Head and Neck / pathology