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Simple Summary  Over the last couple of decades, the prognostic stratification systems of differentiated thyroid cancer (DTC) patients have been revised several times in an attempt to achieve a tailored clinical management reflecting the single patients’ needs. Such revisions are likely to continue in the near future, since the prognostic value of a number of promising clinicopathological features and new molecular biomarkers are being evaluated. Here, we will review the current staging systems of thyroid cancer patients and discuss the most relevant clinicopathological parameters and new molecular markers that are potentially capable of refining the prognosis.    Abstract  Over the last few years, a great advance has been made in the comprehension of the molecular pathogenesis underlying thyroid cancer progression, particularly for the papillary thyroid cancer (PTC), which represents the most common thyroid malignancy. Putative cancer driver mutations have been identified in more than 98% of PTC, and a new PTC classification into molecular subtypes has been proposed in order to resolve clinical uncertainties still present in the clinical management of patients. Additionally, the prognostic stratification systems have been profoundly modified over the last decade, with a view to refine patients’ staging and being able to choose a clinical approach tailored on single patient’s needs. Here, we will briefly discuss the recent changes in the clinical management of thyroid nodules, and review the current staging systems of thyroid cancer patients by analyzing promising clinicopathological features (i.e., gender, thyroid auto-immunity, multifocality, PTC histological variants, and vascular invasion) as well as new molecular markers (i.e., BRAF/TERT promoter mutations, miRNAs, and components of the plasminogen activating system) potentially capable of ameliorating the prognosis of PTC patients.

Papillary Thyroid Cancer Prognosis: An Evolving Field