Biology Beyond the Margins: Impact of 40-Gene Expression Profiling on Risk Stratification in Cutaneous Squamous Cell Carcinoma

Background Cutaneous squamous cell carcinoma (cSCC) causes more annual mortality than metastatic melanoma. However, risk stratification protocols remain based solely on clinicopathologic features, excluding tumor biology. (Table 1) Objective To illustrate how integration of 40-gene expression profile (GEP) testing influences prognostic assessment and post-treatment management in high-risk cSCC. Methods We present a case report of a 70-year-old male whose incidental cSCC was reclassified as high-risk following 40-GEP testing despite histologic clearance, resulting in enhanced surveillance. Results Tumor profiling yielded a Class 2A (higher risk) result, which altered post-operative follow-up strategies beyond conventional staging. Conclusion Gene expression profiling provides valuable, individualized prognostic data, which may improve management of high-risk cSCC patients and should be considered for broader integration into clinical guidelines.