Qualifiers of atypia in the cytologic diagnosis of thyroid nodules are associated with different Afirma gene expression classifier results and clinical outcomes

Abstract

BACKGROUNDThyroid nodules with atypia of undetermined significance (AUS) on fine‐needle aspiration (FNA) have a low risk of malignancy that appears to vary based on specific features described in the AUS diagnosis. The Afirma gene expression classifier (GEC) is a molecular test designed to improve preoperative risk stratification of thyroid nodules, but its performance for different patterns of AUS has not been defined. The objective of this study was to assess GEC results and clinical outcomes in AUS nodules with architectural atypia (AUS‐A), cytologic atypia (AUS‐C) or both (AUS‐C/A).METHODSThis was a retrospective review of all thyroid nodules with AUS cytopathology that underwent GEC testing at the authors' institution over a period of >4 years.RESULTSIn 227 nodules that had AUS cytology results and Afirma GEC testing, the rate of benign GEC results was higher in AUS‐A nodules (70 of 107; 65%) than in AUS‐C/A nodules (25 of 65; 38%; P = .0008), and AUS‐C nodules exhibited an intermediate rate of benign results (27 of 55 nodules; 59%). The risk of cancer among patients who had GEC‐suspicious nodules, 86% of whom underwent resection, was 19% (6 of 25) for AUS‐A nodules compared with 57% (21 of 37) for AUS‐C/A nodules (P = .003) and 45% (10 of 22) for AUS‐C nodules (P = .07). In nodules that had an indeterminate repeat cytology result, no difference was observed in the rate of benign GEC results or in the malignancy rate compared with nodules that had a single cytology result.CONCLUSIONSThe performance characteristics of Afirma GEC testing vary, depending on qualifiers of cytologic atypia. Recognition of these differences may enable clinicians to provide improved counseling and treatment recommendations to patients. Cancer Cytopathol 2017;125:313–322. © 2017 American Cancer Society.

Hurthle cell predominance impacts results of Afirma gene expression classifier and ThyroSeq molecular panel performance in indeterminate thyroid nodules

“…8,9 These tests need to have a high sensitivity and high NPV to effectively reduce unnecessary surgeries. 2,5,7 The strength of the (1) Chronic lymphocytic thyroiditis (2) Follicular adenoma (1) 7,9 In the literature, the NPV for the Afirma GEC for AUS/FLUS and FN is 95% and 94%, respectively, with a sensitivity of 90% for both AUS/FLUS and FN cases.…”

“…Therefore, it is important to identify patients for whom surgical intervention is appropriate to avoid overtreatment. 5 The Afirma GEC measures the expression of 167 genes to identify a benign gene profile with high accuracy. However, approximately 15% to 30% of thyroid nodules have cytologically indeterminate diagnoses rendered by FNA, creating clinical decision-making dilemmas, which highlight the practical limitations of diagnosis by FNA alone.…”

“…In the majority of thyroid FNAs, a definitive benign or malignant diagnosis is assigned. 5,6 ThyroSeq is a mutational panel, which has gone through multiple iterations, with the latest version (V3) examining more than 1000 hotspots of 14 thyroid cancer-related genes and detects 42 types of gene fusion. [1][2][3] The indeterminate category of thyroid nodules includes the atypia of undetermined significance (AUS), follicular lesion of undetermined significance (FLUS), suspicious for follicular neoplasm/follicular neoplasm (SFN/FN), and suspicious for malignancy Bethesda categories from the Bethesda system for reporting thyroid cytopathology.…”

Clinical impact of testing for mutations and microRNAs in thyroid nodules

“…16,17 Multiple studies have described the ability of RNA-based risk classifiers to help resolve diagnostic uncertainty in indeterminate thyroid nodules. [19][20][21] Comparatively, non-coding microRNA based risk classifiers have shown similarly high negative predictive value (NPV) for malignancy and superior positive predictive value when used in combination with analysis for oncogenic mutations and messenger RNA fusion transcripts. 19,20 However, its less than optimal positive predictive value limits the ability to rule in the need for surgery, especially in AUS/FLUS nodules, where malignancy rates are low.…”

Cytomorphologic, Imaging, Molecular Findings, and Outcome in Thyroid Follicular Lesion of Undetermined Significance/Atypical Cell of Undetermined Significance (AUS/FLUS): A Mini-Review

“…A negative Afirma test in aspirated material with the diagnosis of AUS/FLUS will reduce the ROM from 24 to 5%, which justifies the patient observation[87]. …”