**1. Introduction**

Accurate staging of patients affected by differentiated thyroid cancer (DTC) is of crucial importance to ensure the appropriate therapeutic strategy and follow-up, and to ensure the patients' quality of life [1]. To date, several staging systems aimed at estimating the risk of disease-related death or disease relapse/persistence are available. The most employed one is the Tumor-Node-Metastasis (TNM) classification, developed by the American Joint Committee on Cancer (AJCC) [2,3]. The latest version of the TNM system (8th edition/TNM-8) was significantly amended in 2016 with respect to the previous version (7th edition/TNM-7) released in 2009 [3,4]. The 8th edition, while maintaining the classical anatomic extension of the disease as its groundwork, incorporates biological and molecular markers to create a more personalized prognostic stratification [4]. Based on TNM-8, many DTC patients are now included in lower stages and considered to have a reduced risk of dying from thyroid cancer [3,5]. However, in DTC patients the risk of disease recurrence is considerably higher than the risk of disease-related mortality, which makes the TNM staging system, designed to foresee patient survival, uninformative for the prediction of disease recurrence [1,6]. In 2009 the American Thyroid Association (ATA) endorsed a validated risk-stratification system for DTC recurrence in which TNM parameters were implemented by clinicopathological features (i.e., tumor histology, vascular invasion, radioactive iodine uptake, post-operative thyroglobulin serum level, etc.) to divide patients in three risk categories (low, intermediate, and high) [6–8]. Although this model was recognized as a valuable tool in clinical practice, in 2015 the ATA substituted the three-risk-categories-model with a continuum risk model varying from very low risk to high risk of recurrence [1,5]. In the latter, besides TNM and clinicopathological parameters, mutations of BRAF and TERT genes were included [1,6]. In the TNM-8 it has been recommended to take note, in individual patient records, of a number of molecular and clinicopathological parameters that, even if not included in the actual staging system, could be evaluated for inclusion in the next TNM edition [3,4]. They comprise the microscopic extrathyroidal extension, location and number of metastatic lymph nodes, number of lymph nodes sampled and size of the largest metastatic one, extranodal extension, histological subtypes, vascular invasion, postoperative thyroglobulin (Tg) serum level, extension of surgical resection, and molecular characterization [3,9]. In the present work, we retrospectively investigated a case study comprising 1148 patients affected by papillary thyroid cancer (PTC) to evaluate: (i) the effect of the new TNM-8 staging system on patients' risk stratification compared to the previous TNM-7; (ii) the prognostic value of a number of clinicopathological and molecular parameters determined by proportional hazards regression (Cox regression).
