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



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.



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.



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.
Department of Medicine, The Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Sylvan C
SC
Baca
Department of Pathology, The Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Kristine S
KS
Wong
Department of Pathology, The Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Kyle C
KC
Strickland
Department of Radiology, The Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Howard T
HT
Heller
Thyroid Section, Division of Endocrinology, Hypertension, and Diabetes, The Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Matthew I
MI
Kim
Department of Pathology, The Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Justine A
JA
Barletta
Department of Pathology, The Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Edmund S
0000-0003-1987-2004
ES
Cibas
Department of Pathology, The Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Jeffrey F
0000-0001-7768-3901
JF
Krane
Thyroid Section, Division of Endocrinology, Hypertension, and Diabetes, The Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Ellen
E
Marqusee
Thyroid Section, Division of Endocrinology, Hypertension, and Diabetes, The Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Trevor E
TE
Angell
D018263:Adenocarcinoma, Follicular / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000236:Adenoma / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D044963:Biopsy, Fine-Needle; D002277:Carcinoma / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary; D003581:Cytodiagnosis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D018570:Risk Assessment; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016606:Thyroid Nodule / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D059467:Transcriptome; D047368:Tumor Burden
Afirma gene expression classifier; architectural atypia; atypia of undetermined significance (AUS); cytologic atypia; cytology; follicular lesion of undetermined significance (FLUS); indeterminate cytology; thyroid nodule