Afirma Thyroid FNA Analysis

The Evolved Solution for Improved Thyroid Nodule Assessment

An Unmet Clinical Need is Addressed

Approximately 525,000 thyroid nodule fine needle aspiration (FNA) procedures were performed in the United States in 2011.1 FNA samples can be challenging to interpret and produce indeterminate results in 15% to 30% of cases.2

Current guidelines recommend that most of these patients undergo a diagnostic thyroid surgery to assess whether the nodules are benign or malignant.2,3 Approximately 70% to 80% of the time, the nodules prove to be benign for cancer by surgical pathology.4,5

The novel Gene Expression Classifier (GEC), the centerpiece of the Afirma Thyroid FNA Analysis, helps physicians reduce the number of avoidable surgeries by preoperatively identifying benign nodules among those that were originally classified by cytopathology as indeterminate. The GEC measures the expression of 142 genes and applies a multi-dimensional algorithm to reclassify a nodule with cytopathology indeterminate diagnosis as benign or suspicious.6 The final gene set resulted from a whole genome approach that assessed the 22,000 genes (247,000 transcripts) in the human genome.7

The GEC Forms the Centerpiece of the Afirma Thyroid FNA Analysis

The Afirma Thyroid FNA Analysis combines specialized cytopathology and the novel Afirma GEC for improved thyroid nodule diagnosis. Physicians submit to Veracyte thyroid nodule FNA samples collected in a single patient visit. Then, a thyroid cytopathology specialist at Thyroid Cytopathology Partners (TCP), an independent partner of Veracyte, performs cytopathology assessment of a thyroid nodule FNA sample under the microscope. If the cytopathology diagnosis is benign or malignant, the analysis is complete. Only when TCP's cytopathology diagnosis is indeterminate* (TCP’s indeterminate rate to date has been 14% to 17%) is the proprietary Gene Expression Classifier performed.

The TCP team reads thousands of cases each month, making them what we believe to be the largest thyroid-only cytopathology group.8 Their volume and specialization expose them to rare neoplasms, including medullary thyroid cancer, on a routine basis.9 In addition, they have implemented processes to ensure quality and consistency is maintained.8 Learn more about TCP at

Clinical Validity, Utility and Cost Effectiveness of the Afirma Gene Expression Classifier

A large, multi-center (49 sites), prospective clinical validation study published in the New England Journal of Medicine (NEJM) in 2012 demonstrated that thyroid nodules with indeterminate cytopathology and a benign GEC result have less than 6% likelihood of being malignant (greater than 94% Negative Predictive Value).6 These results, consistent with earlier findings,9 show the risk of malignancy of a GEC benign result is comparable to that of nodule diagnosed as benign by cytopathology.4,5 As a result, the authors of the NEJM study and an associated editorial suggest that physicians can consider watchful waiting in lieu of surgery in patients with cytopathology indeterminate and GEC benign results.6,10

A subsequent clinical utility study published in Thyroid showed that, among 51 endocrinologists, when their patient had an indeterminate cytopathology result and a benign GEC result, physicians recommended surgery in only 7.6% of these cases. This represents a 90% reduction in surgeries when compared to the historical average for patients with cytopathology indeterminate results alone.11 Marrying these results with cost-effectiveness modeling conducted by researchers at the Johns Hopkins School of Public Health and School of Medicine (Endocrinology) suggests that incorporating the Afirma GEC into routine practice can improve quality of life and remove cost from the healthcare system.11,12 Further, we believe the GEC is currently the only diagnostic test that meets the criteria of the National Comprehensive Cancer Network (NCCN) for safely mointoring patienst with indeterminate cytopathology reuslts in lieu of surgery.

A Comprehensive Patient-centric Approach to Thyroid Nodule Management

By combining specialized cytopathology and the Gene Expression Classifier, the Afirma Thyroid FNA Analysis:
  • Enables physicians to identify patients who may avoid surgery5,7,10,11
  • Empowers confident and timely clinical decisions from a single patient visit8
  • Gives patients access to specialized cytopathology and robust science5,7-9,11
  • Integrates seamlessly into a physician's practice workflow.
  • Ensures quality and convenience in collecting and shipping patient samples8,13
  • Allows patients to receive better care at a lower cost5,10,12

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* Indeterminate includes Follicular Lesion of Undetermined Significance (FLUS)/Atypia of Undetermined Significance (AUS) and (suspicious for) Hürthle/Follicular Neoplasm.
1. Sosa JA, Hanna J, Lanman RB, Robinson KA, Ladenson PW. Increases in thyroid nodule fine needle aspirations, surgeries and diagnoses of thyroid cancer in the United States. American Association of Endocrine Surgeons 34th Annual Meeting, Apr 14-16, 2013. Chicago, Ill. (oral abstract).
2. Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid.2009;19:1167-1214.
3. Gharib H, Papini E, Paschke R, Duick DS, Valcavi R, Hegedüs L, et al. American Association of Clinical Endocrinologists, Associazione Medicie Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules: executive summary of recommendations. Endocr Pract. 2010;16(S1):1-43.
4. Wang CC, Friedman L, Kennedy GC, Wang H, Kebebew E, Steward DL, et al. A Large Multicenter Correlation Study of Thyroid Nodule Cytopathology and Histopathology. Thyroid. 2011;21:243-251.
5. Lewis CM et al. Thyroid Fine-Needle Aspiration Biopsy: Variability in Reporting 2009 Thyroid 19(7) 717-722.
6. Alexander EK, et al. Preoperative Diagnosis of Benign Thyroid Nodules with Indeterminate Cytology. N Engl J Med. 2012;367:705-715.
7. Chudova D, Wilde JI, Wang ET, Wang H, Rabbee N, Egidio CM, et al. Molecular Classification of Thyroid Nodules Using High-Dimensionality Genomic Data. J Clin Endocrinol Metab. 2010;95:5296-5304.
8. Data on File. Veracyte, Inc.
9. Kloos KT, O’Reilly K, Traweek ST, et al. Novel Gene Expression Classifier Raises Pre-operative Suspicion of Thyroid Cancer. [Poster 1332] 21st Annual Meeting and Clinical Congress of American Association of Clinical Endocrinology, Philadelphia, PA. May 23-27, 2012.
10. Jameson JL, Minimizing Unnecessary Surgery for Thyroid Nodules, N Engl J Med. 2012;367:765-767
11. Duick DS, Klopper JP, Diggans JC,Friedman L, Kennedy GC, Lanman RB, et al. The impact of benign gene expression classifier test results on the endocrinology decision-to-operate in patients with thyroid nodules with indeterminate FNA cytopathology. [Poster 1108] 21st Annual Meeting and Clinical Congress of American Association of Clinical Endocrinology, Philadelphia, PA. May 23-27, 2012.
12. Li H, Robinson KA, Anton B, Saldanha IJ, Ladenson PW. Cost-Effectiveness of a Novel Molecular Test for Cytologically Indeterminate Thyroid Nodules. J Clin Endocrinol Metab. 2011;96:E1719-E1726.
13. Walsh S, Wilde JI, Tom E, et al. Analytical Verification of a Novel Gene Expression Test which Identifies Benign Thyroid Nodules in Patients with Indeterminate Fine Needle-Aspiration (FNA) Cytology. [Abstract 1098] 2011 Late Breaking Abstracts of the 20th Annual Meeting and Clinical Congress of American Association of Clinical Endocrinology, San Diego, CA, April 2011, p 2–3.

Afirma Thyroid FNA Analysis Description
The Afirma Thyroid FNA Analysis is a diagnostic service provided by Veracyte, Inc. for the assessment of thyroid nodules. Patient samples obtained through fine needle aspirate (FNA) biopsies are collected for both cytopathology assessment and the Gene Expression Classifier. Initially, cytopathology assessment is conducted. If the cytopathology diagnosis is benign, suspicious for malignancy, malignant or nondiagnostic, the Afirma Thyroid FNA Analysis is complete. If the cytopathology diagnosis is indeterminate (includes Follicular Lesion of Undetermined Significance (FLUS)/Atypia of Undetermined Significance (AUS) and (suspicious for) Hürthle/Follicular Neoplasm), the thyroid nodule is greater than or equal to 1 cm and the patient is 21 years or older, the Gene Expression Classifier is performed. The Gene Expression Classifier determines the expression profile of RNA isolated from the nodule to be benign or suspicious for malignancy. Clinical correlation of the Afirma Thyroid FNA Analysis result is recommended. The Afirma Gene Expression Classifier and its performance characteristics were determined by Veracyte. Afirma Thyroid FNA Analysis is used for clinical purposes.
Veracyte’s laboratory operations are headquartered at our CLIA-certified laboratory in South San Francisco, California, where we perform all GEC testing. Beginning in May 2013, our customers began shipping samples to our laboratory in Austin, Texas. Once received, samples are processed through our automated accessioning system, prepared for cytopathology review, and delivered to TCP for cytopathology analysis. If an FNA sample is diagnosed as indeterminate following cytopathology, the sample is transferred to South San Francisco where we perform GEC testing. Our South San Francisco facility is responsible for quality assurance oversight, licensing and regulation compliance and maintenance for both of our laboratories to ensure data integrity and consistent, validated processes.
Veracyte Laboratory Licenses: CLIA: 05D2014120 California: CLF340176