The Bethesda system for reporting thyroid cytopathology: into the clinic

Abstract

Howard H Wu, Matthew J Swadley Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA Abstract: Fine-needle aspiration (FNA) remains the most effective and safe method of evaluating thyroid nodules for potential surgical management. Since 2007, the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has standardized nomenclature for thyroid FNA and provided an evidence-based malignancy risk for each of its diagnostic categories. Using TBSRTC criteria, most thyroid nodules can effectively be categorized as either “benign” or “malignant” and referred for definitive management without further testing. However, many thyroid nodules fall into an indeterminate TBSRTC category, most notably atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS). Efforts have been made to elucidate further clinical utility from indeterminate cases, including nomenclature modifications and molecular-based testing modalities. The use of “atypia qualifiers” in AUS/FLUS cases appears to refine the diagnosis to provide a more specific risk of malignancy. Notably, AUS qualifiers of “cannot exclude papillary thyroid carcinoma” and “cannot exclude follicular neoplasm” appear to carry a higher risk of malignancy than other AUS qualifications in multiple studies. Molecular panels appear to hold particular promise as adjuncts in helping to delineate worrisome from non-worrisome thyroid nodules with indeterminate cytology. In particular, the miRInform test (Asuragen), an oncogene mutation panel, appears to show utility in its ability to “rule in” a malignant or neoplastic process, although it is limited by a relatively high false-negative rate. Conversely, the Afirma test (Veracyte), a gene expression classifier (GEC), appears to show clinical promise due to its high negative predictive value; albeit with a significant false-positive rate. Herein, we provide an overview of TBSRTC diagnostic categories and a literature review of new attempts to further refine indeterminate categories; as well as a review of the most commonly used commercial molecular panels used in thyroid cytopathology. Keywords: thyroid, FNA, the Bethesda system, cytopathology