title: Performance of the Afirma Gene Expression Classifier in Hürthle Cell Thyroid Nodules Differs from Other Indeterminate Thyroid Nodules.
abstract: BACKGROUND
  The recently introduced Afirma gene expression classifier (AGEC) provides binary results (benign or suspicious) to guide management of cytologically indeterminate thyroid nodules. The AGEC is intended to reduce unnecessary surgeries for benign nodules, and management algorithms favor surgery for suspicious results. Limited data are available on the performance of this test for Hürthle cell nodules (HCNs). This study hypothesized that a predominance of Hürthle cells leads to an increased rate of suspicious AGEC results with a potential for overtreatment, despite a relatively low risk of malignancy.
  
  
  METHODS
  The pathology databases from three tertiary care facilities were queried from 2010 to 2014 for fine-needle aspirates (FNAs) diagnosed as suspicious for Hürthle cell neoplasm (SHCN) or atypia of undetermined significance/follicular lesion of undetermined significance concerning for Hürthle cell neoplasm (AFHCN). Cytology diagnoses were rendered internally prior to AGEC testing. The patient demographics, FNA diagnosis, AGEC result, surgical procedure, and pathologic outcomes were recorded.
  
  
  RESULTS
  The cohort consisted of 134 patients with HCNs. Prior to AGEC availability, 62 patients underwent surgery: 81% (50/62) of patients had surgery, and 34% (17/50) of the resected index nodules were malignant. After introduction of the AGEC, 72 patients underwent AGEC testing: 65% (47/72) of patients had surgery, and 13% (6/46) of the resected nodules were malignant. Thirty-two percent (23/72) of patients had a benign AGEC result and did not undergo surgery, and 4% (3/72) had surgery despite a benign AGEC result with benign final pathology, whereas 63% (45/72) of patients had suspicious AGEC results, with 96% of these patients (43/45) undergoing surgery, and 14% (6/43) of these index nodules were malignant.
  
  
  CONCLUSIONS
  While 32% of tested patients declined surgery based on a benign AGEC, 86% of patients with suspicious AGEC findings had unnecessary surgery, reflecting a substantially lower rate of malignancy from what was previously reported for all indeterminate nodules. Given the approximate pretest malignancy risk of 25-35% for an FNA diagnosis of SHCN or AFHCN, a suspicious AGEC diagnosis does not increase the probability of malignancy in an HCN, and patients should be counseled accordingly.
authors.affiliation: 1 Department of Surgery, Massachusetts General Hospital , Boston, Massachusetts.
authors.forename: Eran
authors.initials: E
authors.lastname: Brauner
authors.affiliation: 2 Department of Pathology, Massachusetts General Hospital , Boston, Massachusetts.
authors.forename: Brittany J
authors.initials: BJ
authors.lastname: Holmes
authors.affiliation: 3 Department of Pathology, Brigham and Women's Hospital , Boston, Massachusetts.
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Krane
authors.affiliation: 4 Department of Pathology, Beth Israel Deaconess Medical Center , Boston, Massachusetts.
authors.forename: Michiya
authors.initials: M
authors.lastname: Nishino
authors.affiliation: 5 Departments of Surgery and Anesthesia, Boston Children's Hospital , Boston, Massachusetts.
authors.forename: David
authors.initials: D
authors.lastname: Zurakowski
authors.affiliation: 6 Department of Medicine, Beth Israel Deaconess Medical Center , Boston, Massachusetts.
authors.forename: James V
authors.initials: JV
authors.lastname: Hennessey
authors.affiliation: 2 Department of Pathology, Massachusetts General Hospital , Boston, Massachusetts.
authors.forename: William C
authors.initials: WC
authors.lastname: Faquin
authors.affiliation: 1 Department of Surgery, Massachusetts General Hospital , Boston, Massachusetts.
authors.forename: Sareh
authors.initials: S
authors.lastname: Parangi
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000175:diagnosis / Q000235:genetics*; D018249:Adenoma, Oxyphilic; D000328:Adult; D000368:Aged; D044963:Biopsy, Fine-Needle; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics*; D018278:Carcinoma, Neuroendocrine / Q000175:diagnosis / Q000235:genetics*; D002291:Carcinoma, Papillary; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D024862:Oxyphil Cells / Q000378:metabolism* / Q000473:pathology; D012189:Retrospective Studies; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000235:genetics*; D016606:Thyroid Nodule / Q000175:diagnosis / Q000235:genetics*