Impact of the 3rd edition of The Bethesda System for Reporting Thyroid Cytopathology on Grey Zone Categories

Introduction: Thyroid Bethesda Reporting System is a six-tiered system that aims to bring uniformity in reporting thyroid cytology and improve the communication with clinicians. The system has achieved its goal as a presurgical diagnostic method; however, it remains a screening method in the grey zone categories, namely atypia of undetermined significance (AUS) and follicular neoplasm (FN). The book recently released the 3rd edition, following the recent changes in thyroid pathology. One of the most important novelties is subgrouping AUS category and FN to be able to make a better risk stratification in these categories. Our group aims to retrospectively analyze a large dataset based on the new TBSRTC, with a focus on the grey zone categories. Methods: Only patients who underwent lobectomy or total thyroidectomy were included, allowing for direct comparison between cytological and histopathological results. Cytological evaluations, based on the TBSRTC 3rd edition, were methodically compared with their respective histopathological results, enabling a comprehensive analysis. Results: Of the 244 patients (Female:Male ratio = 8.8:1, Mean age = 56), a total of 252 nodules were evaluated. A distinction was noted with 79 nodules (31%) diagnosed as AUS and 173 nodules (69%) as FN. Intriguingly, the ROM for AUS-overall stood at 44.3%, with AUS-nuclear atypia at 50% and AUS-other at 43.2%. Although the AUS sub-divisions did not demonstrate statistical significance, a significant disparity was observed in their distribution, with 15% as AUS-nuclear atypia compared to 85% as AUS-other. This disparity raises the question: Could AUS-other be considered the new waste-basket category in the TBSRTC 3rd edition? Using the TBSRTC 3rd edition as a base, we added a subclassification for FN nodules based on the presence or absence of PTC nuclear features. Our findings showed that differentiating FN with oncocytic characteristics correlated well with histological outcomes and ROMs. Though retrospective in design with inherent bias potential, our data suggests a possible improvement in PTC case segregation in the FN category when differentiating between FN nodules with and without PTC nuclear features. Conclusion: Our retrospective study sheds light on the potential advantages of the TBSRTC 3rd edition, particularly in refining the AUS and FN categories for thyroid nodules. The clear disparity in AUS sub-categories raises important questions about their classification and potential future refinements. Moreover, the differentiation of FN nodules based on PTC nuclear features holds a promising approach for better risk stratification.