Study Fails to Validate Perineural Invasion Score as a Predictor of Adverse Events in cSCC

A new study evaluating the relationship between perineural invasion (PNI) score and adverse events (AE) in cutaneous squamous cell carcinoma (cSCC), presented at the 2025 AAD Annual Conference, found no statistically significant association. These findings do not support the predictive value of the composite PNI score for metastasis, recurrence, or disease-related death in patients with cSCC. 

The study sought to validate the Totonchy et al. findings, which previously demonstrated a positive correlation between a higher PNI score and increased risk of AE. Researchers analyzed histopathologic slides from 58 patients with cSCC, evaluating 5 components of perineural invasion: 

- Largest affected nerve diameter 

- Number of nerves involved 

- Depth of nerve involvement 

- Intra- vs extra-tumoral PNI 

- Focal vs circumferential PNI 

The results showed that the median composite PNI score was 4.0 in patients without AE and 5.0 in those who experienced AE, but this difference was not statistically significant (P=0.949). 

"This study did not find any statistically significant association between the composite or individual components of the PNI score and AE in cSCC," the authors reported. 

Further statistical analysis of individual PNI components also revealed no significant correlation with AE. The P values for nerve diameter (0.389), number of nerves involved (0.373), nerve depth (0.426), intra- vs extra-tumoral nerve involvement (0.763), and focal vs circumferential PNI (0.300) all failed to reach significance. 

The study concludes that PNI scoring alone may not be a reliable tool for predicting adverse events in cSCC and emphasizes the need for larger studies to further evaluate this potential prognostic marker. 

"Additional studies with larger sample sizes are needed to assess if PNI score can reliably predict AE in patients with cSCC," the authors noted. 

For practicing dermatologists, these findings suggest that PNI should not yet be used as a standalone factor for prognostication in cSCC. Until further validation is achieved, clinical decision-making should continue to rely on a combination of histopathologic, clinical, and staging criteria to assess patient risk.

Reference
The use of perineural invasion score as a predictor for adverse events in patients with cutaneous squamous cell carcinoma: a validation study. News Release. presented at: AAD Annual Meeting; March 7–11, 2025; Orlando, FL.