Molecular pathology and diagnostics of cutaneous malignancy

Abstract

Advances and discoveries in molecular genetics over the past decade have literally changed the face of diagnosis and treatment decisions for patients with melanoma and non-melanoma skin cancer. These include genetic analysis of skin biopsies as a diagnostic aid, genotyping of tumors from patients with malignant melanoma for personalized treatment of metastatic disease, and discovery of a new virus thought to play a role in the pathogenesis of Merkel cell carcinoma. Initiated by the discovery of a familial cancer gene in patients with familial melanoma and atypical nevi over three decades ago, molecular pathology techniques now play a central role in genetic testing for melanoma risk, in evaluation of melanocytic proliferations with uncertain biologic potential, and in stratifying patients with metastatic melanoma for treatment with targeted therapeutic agents, driving the search for better markers of prognosis and response to therapy. Targeted therapy is now available for treatment of unresectable or metastatic basal cell carcinoma. It is likely that continual improvements in techniques for analyzing blood and fresh and archival tumor tissue will uncover the pathogenesis of skin tumors related and unrelated to sun exposure, spawn the development of vaccinations or chemopreventive agents for these tumors, and enable physicians to customize treatment based on unique patient and tumor characteristics. This chapter will highlight relevant information concerning the molecular pathogenesis of melanoma, basal and squamous cell carcinoma, and Merkel cell carcinoma. Sections on molecular techniques available for diagnosis, prognosis, and treatment selection, emphasizing melanoma where this is most highly developed, are included.