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Presentation

Dermatopathology Perspectives on Risk Stratification and Multidisciplinary Management of Cutaneous Squamous Cell Carcinoma

Description

The presentation focused on the dermatopathologist’s role in risk stratifying cutaneous squamous cell carcinoma (cSCC) and communicating high-risk features that influence staging, surveillance, and treatment. The speaker emphasized that histopathology remains central to NCCN, AJCC, and BWH staging, but grading and features like perineural invasion can be subjective, variable, and sometimes missed due to limited biopsy sampling, Mohs margin-focused specimens, tumor heterogeneity, or mimics such as peritumoral fibrosis. The talk reviewed treatment options beyond surgery, including immunotherapy and radiation, noting that adjuvant radiation is considered for high-risk disease but is not appropriate in some settings such as prior radiation or photosensitive disorders. Emerging tools such as gene expression profiling and circulating tumor DNA were presented as ways to improve biologic risk assessment and surveillance, and standardized pathology approaches may outperform traditional staging alone in predicting metastatic risk. The discussion also covered multidisciplinary management with tumor boards, the evolving role of sentinel lymph node biopsy, and practical use of ctDNA and GEP in selecting patients for closer follow-up or adjuvant therapy. Audience questions further explored hedgehog inhibitors, adjuvant immunotherapy for extensive PNI, ctDNA logistics, and how molecular testing and imaging are being integrated into personalized care for high-risk cSCC.

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Conclusions

High-risk cutaneous squamous cell carcinoma should be managed with a multidisciplinary team rather than surgery alone.
Pathology remains central to risk stratification, but grading and perineural invasion assessment are subjective and can be missed or misclassified.
Current staging systems such as AJCC and BWH are useful but incompletely capture metastatic risk and depend heavily on limited histologic sampling.
Radiation therapy is an important option when surgery is not feasible and is also valuable as adjuvant treatment for high-risk features such as positive margins, perineural spread, and poor differentiation.
Immune checkpoint inhibitors, especially PD-1 blockade, are increasingly important for advanced disease and may also be useful in adjuvant or neoadjuvant settings.
Ancillary tools like gene expression profiling, circulating tumor DNA, and standardized or computational pathology can improve prediction of recurrence and metastasis beyond traditional histology.
Circulating tumor DNA may provide early warning of residual or recurrent disease and could help guide surveillance and escalation of therapy.
Deep learning or other standardized pathology approaches may outperform conventional staging systems in predicting metastatic potential.
Because traditional histopathology can undercall biologic aggressiveness, apparently lower-risk tumors may still behave aggressively and warrant additional testing or follow-up.
Combining surgery with radiation and/or systemic therapy can reduce recurrence risk in appropriately selected high-risk patients.

Bichakjian et al., Practical Radiation Oncology, 2019 — Radiation therapy for basal and squamous cell skin cancers.
Wysong et al., JAMA Dermatology 2020.
Ruiz et al., JAAD 2021.
Reinert et al., Nat Med 2019.
Parikh et al., JCO Precis Oncol 2021.
Peritumoral Fibrosis in Basal Cell and Squamous Cell Carcinoma Mimicking Perineural Invasion: Potential Pitfall in Mohs Micrographic Surgery.#10.1016/s0093-3619(08)70232-6
npj Precision Oncology article on enhanced metastasis risk prediction in cutaneous squamous cell carcinoma using deep learning and computational histopathology.#10.1038/s41698-025-01065-7
National Comprehensive Cancer Network (NCCN) Squamous Cell Skin Cancer Guidelines.
ASTRO Clinical Practice Guideline.