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

Abstract

Background: Thyroid 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).

Methods: This 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.

Results: In 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.

Conclusions: The 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.

Keywords: Afirma gene expression classifier; architectural atypia; atypia of undetermined significance (AUS); cytologic atypia; cytology; follicular lesion of undetermined significance (FLUS); indeterminate cytology; thyroid nodule.

Figure 1

Afirma gene expression classifier (GEC) results and pathologic outcomes are illustrated in thyroid nodules with different qualifiers of atypia on cytologic assessment. Pie charts comparing the proportion of Afirma GEC results that were benign (green) and suspicious (red) in thyroid nodules with a cytologic diagnosis of atypia of undetermined significance (AUS) and a qualifier of either (Left) architectural atypia (AUS‐A), (Middle) cytologic atypia (AUS‐C), or (Right) cytologic and architectural atypia (AUS‐C/A) reveal a significant difference in the proportion of GEC results between AUS‐A and AUS‐C/A nodules (P = .0008). In thyroid nodules with a suspicious GEC result that underwent surgical resection, providing a histopathologic gold‐standard diagnosis, bar graphs display the proportion of benign and malignant outcomes between AUS‐A, AUS‐C, and AUS‐C/A nodules and indicate a significant difference in the malignancy rate between AUS‐A and AUS‐C/A nodules (P = .003).