Dermatopathology Perspective on Risk Stratification and Management of Cutaneous Squamous Cell Carcinoma

Conclusions

• Cutaneous squamous cell carcinoma is highly heterogeneous, and histologic grading alone is often subjective and inconsistent across observers.
• Accurate risk stratification is crucial because it influences prognosis, surveillance intensity, and treatment selection for patients with high-risk cSCC.
• Current staging systems such as AJCC and BWH rely heavily on pathologic high-risk features, but these features are sometimes incompletely sampled or difficult to identify reliably.
• Perineural invasion and other high-risk findings can be missed or overcalled because of limited tissue, mixed tumor morphology, and mimics such as peritumoral fibrosis.
• High-risk cSCC should be managed in a multidisciplinary setting, with coordinated input from dermatology, Mohs surgery, radiation oncology, and head and neck surgery when appropriate.
• Radiation therapy is an important alternative to surgery when surgery is not feasible or declined, and it is also used as adjuvant treatment for selected high-risk tumors.
• Immune checkpoint inhibitors and other systemic therapies provide effective options for advanced or metastatic cSCC and can reduce recurrence risk in appropriate settings.
• Emerging tools such as gene expression profiling, circulating tumor DNA, and standardized or AI-assisted pathology may improve risk prediction beyond conventional histopathology.
• Although conventional histopathology remains foundational, better objective biomarkers and computational approaches are needed to more accurately predict metastatic behavior.
• The overall message is that better risk stratification can improve treatment decisions and outcomes, especially by identifying patients who may benefit from radiation or combination medical therapy in addition to surgery.