Pitfalls in Thyroid Fine-Needle Aspiration Cytopathology: An Approach to Atypical Findings

Abstract

Background: Thyroid nodules are prevalent among the general population, thus imposing substantial demands upon healthcare providers to establish effective management paradigms when investigating these lesions. A pivotal component in the diagnostic process involves the cytomorphological evaluation of fine-needle aspiration (FNA) specimens extracted from the nodule under scrutiny. This examination serves the critical purpose of enabling a comprehensive assessment for the risk of either a neoplasm or malignancy, thereby providing the clinical team with the requisite information to render decisions regarding potential surgical intervention and/or a structured clinical follow-up. A subset of FNA specimens obtained from the thyroid gland present a vexing challenge for interpretation and cannot be classified based on cytomorphology as either benign or malignant and are classified as “indeterminate” for neoplasm or malignancy. The indeterminate thyroid FNA diagnosis in the third iteration of the Bethesda classification is termed as “atypia of undetermined significance” (AUS). Summary: The thyroid FNA specimens classified as “atypical” constitute a perplexing category, necessitating considerations such as repeated cytological evaluations, supplementary molecular analyses, diagnostic lobectomy, or vigilant surveillance. This review article draws upon the most recent Bethesda classification guidelines and delineates various potential pitfalls encountered during the interpretation of atypia observed in thyroid fine-needle aspiration and histopathologic counterparts. Additionally, it proffers strategic algorithms devised to effectively navigate these diagnostic challenges. Key Messages: It is important to recognize the value of an integrated approach when triaging AUS lesions, considering various clinical, morphological, and sometimes also immunocytochemical or molecular features.