BACKGROUND: Recent molecular studies have described a number of abnormalities associated with the progression and dedifferentiation of thyroid carcinoma. These distinct molecular events are often associated with specific stages of tumor development. A better understanding of the mechanisms involved in thyroid cancer pathogenesis may help to translate these discoveries toward improvements in patient care. METHODS: We reviewed the literature on the molecular pathogenesis of thyroid cancer and compared clinical, histopathologic, and genetic features important in defining the disease process. RESULTS: The progression of thyroid cancer from well-differentiated to poorly differentiated and undifferentiated carcinoma represents a biological continuum. Specific genetic events serve as early initiating and late triggering events. Poorly differentiated thyroid carcinomas occupy an intermediate position in this progression model. CONCLUSIONS: With sophisticated genetic tools generating a wealth of information, we have gained better insight into the mechanisms driving thyroid tumor progression. Recognition of these features is crucial to the management of patients with thyroid cancer. Novel treatments are being designed based on our enhanced understanding of this disease process.
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