4. Melanoma. Part I. Risk Assessment, Diagnosis, and Prognosis: Using Molecular Tools to Diagnose Melanoma, Predict Its Behavior, and Evaluate for Inheritable Forms

For the past 200 years, the diagnosis of melanoma relied upon standard clinical and histologic criteria. Early diagnosis with surgical intervention had been the only chance for cure. Recent deciphering of melanoma’s genetic underpinnings and signaling pathways, however, has revolutionized the complete management of the melanoma patient. Assessment of patient risk is no longer limited to ultraviolet exposure but includes evaluation of the patient’s genome. Diagnosis is no longer limited to clinical and microscopic inspection of the tumor, but includes assessment of the tumor’s genome for chromosomal abnormalities and signaling molecule mutations. Prognosis is no longer linked only to tumor size but can be impacted by the amplification of tumor oncogenes and/or the molecular detection of micrometastases. And, finally, treatment is no longer limited to “excise and pray” tactics but can be tailored to the individual, reversing the action of the very mutations that led to melanomagenesis. With these new molecular tools, it is now clear that melanoma is not a single tumor but a complex array of tumors, each with a unique molecular profile, similar only in their genesis within a host melanocyte. This chapter begins the discussion on melanoma, exploring the role of molecular diagnostics in assessing patient risk (i.e., hereditary melanoma), diagnosis, prognosis, and reclassification schemes, with the focus on practical, or current, applications.