Interobserver Variation in Evaluating Perineural Invasion for Oral Squamous Cell Carcinoma: Phase 2 Survey Study

Flora Yan, Yi Shing Lisa Cheng, Nora Katabi, Shaun A. Nguyen, Huey Shys Chen, Patrick Morgan, Kathy Zhang, Angela C. Chi

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


In a previous study, we found interobserver agreement among 88 board-certified pathologists evaluating perineural invasion (PNI) in oral squamous cell carcinoma (OSCC) was fair, and participants most often used the following criteria: (1) tumor invading the perineurium, (2) tumor surrounding a nerve. In this study, we aimed to determine whether application of these most commonly used criteria may improve interobserver agreement. 512 pathologists were invited to participate in a web-based survey. Participants were asked to assess the presence/absence of PNI in a set of OSCC photomicrographs by applying each of the two criteria above. The survey was completed by 84 board-certified pathologists [mean age: 52 years (range 31–81), mean years in practice: 19 (range 1–56)]. Interobserver agreement was moderate (k = 0.46, 95% CI 0.45–0.46) when using definition #1 (tumor invading the perineurium) and fair (k = 0.24, 95% CI 0.23–0.25) when using definition #2 (tumor surrounding a nerve). By comparison, interobserver agreement was fair (k = 0.36, 95% CI 0.35–0.37) among phase 1 participants asked to evaluate these photomicrographs as they would in their pathology practice. Differences in kappa between definition #1 and phase 1, definition #2 and phase 2, and definition #1 and #2 were statistically significant (p < 0.001). Compared to our prior study based on pathologists’ personal views, the current study shows improved interobserver agreement with application of the criterion, “tumor invading the perineurium.” However, further work is needed to delineate concise, objective, and more reproducible criteria for histopathologic assessment of PNI.

Original languageEnglish (US)
Pages (from-to)935-944
Number of pages10
JournalHead and Neck Pathology
Issue number3
StatePublished - Sep 2021
Externally publishedYes


  • Interobserver Agreement
  • Oral Cavity
  • Pathologists
  • Perineural Invasion
  • Squamous Cell Carcinoma
  • Survey

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Otorhinolaryngology
  • Oncology


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