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Background  Papillary Thyroid Cancer (PTC) is the most common endocrine malignancy, with recurrence rate as high as 30%. A great deal of controversy surrounds the significance of microscopic extrathyroidal extension (m-ETE) as a prognostic factor. The most recent edition (8 th ) of American Joint Committee on Cancer (AJCC) staging system has removed m-ETE from the definition of pT3, which suggests that m-ETE may lack prognostic impact in PTC patients. Moreover, data about m-ETE prevalence and clinical impact on Middle Eastern PTC remains unknown. We therefore investigate the prevalence of m-ETE and its clinico-pathological correlation and prognostic impact in Middle Eastern PTC. We also compared the AJCC 7 th  and 8 th  staging systems and their prognostic performance.    Methods  PTCs from 1430 consecutive adult (&amp;gt; 18 years) patients from single tertiary care hospital were included in this study. A retrospective analysis of PTC patients’ survival and recurrence were compared between AJCC 8 th  and AJCC 7 th  staging systems using Proportion of Variation Explained (PVE) and Harrell’s C-index.    Results  Median follow up of the study cohort was 9.3 years. 31.2% (446/1430) of patients had m-ETE. In the overall cohort, m-ETE was associated with multiple adverse features such as older age (p &amp;lt; 0.0001), male sex (p = 0.0245), tall cell variant (p &amp;lt; 0.0001), bilateral tumors (p &amp;lt; 0.0001), multifocality (p &amp;lt; 0.0001), lymphovascular invasion (p &amp;lt; 0.0001), lymph node metastasis (p &amp;lt; 0.0001), distant metastasis (p = 0.0166), tumor recurrence (p &amp;lt; 0.0001), radioactive iodine refractoriness (p &amp;lt; 0.0001),  BRAF  mutation (p &amp;lt; 0.0001) and reduced recurrence-free survival (RFS; HR = 1.75; 95% CI = 1.30 – 2.35; p &amp;lt; 0.0001) irrespective of tumor size. Of the 611 patients with T3 disease based on AJCC 7 th  edition, 359 (58.8%) were down-staged in AJCC 8 th  edition classification. Overall, the prognostic performance of AJCC 8 th  edition was inferior to AJCC 7 th  on the basis of lower PVE (3.04%  vs . 3.73%) and lower C-index (0.40  vs . 0.48).    Conclusions  In Middle Eastern PTC, m-ETE is significantly associated with compromised survival and acts as an independent predictor of RFS. Given these findings, m-ETE should be included in the thyroid cancer treatment guidelines.

frontiers in oncology

Microscopic Extrathyroidal Extension Results in Increased Rate of Tumor Recurrence and Is an Independent Predictor of Patient’s Outcome in Middle Eastern Papillary Thyroid Carcinoma