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The 2015 American Thyroid Association (ATA) Guidelines

The current ATA Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer (1) contain specific recommendations addressing the diagnostic use of molecular testing for thyroid nodules with Bethesda III-IV cytology (Recommendations 15 and 16) and for informing the extent of surgery (Recommendations 17, 19, 20).

  Recommendation 15 states that for nodules with AUS/FLUS cytology, investigation such as repeat FNA or molecular testing may be used to supplement malignancy risk assessment (Weak recommendation, Moderate-quality evidence).

  Recommendation 16 states that for the management of follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) cytology nodules, molecular testing may be used to supplement malignancy risk assessment data (Weak recommendation, Moderate-quality evidence).

  Recommendation 17 states that mutational testing for BRAF or the mutation marker panel (BRAF, RAS, RET/PTC, PAX8/PPARγ, etc.) may be considered in nodules with suspicious for malignancy cytology (Bethesda V) if such data would be expected to alter surgical decision-making (Weak recommendation, Moderate-quality evidence).

  Recommendation 19 states that when surgery is considered for patients with a cytologically indeterminate nodule, recommendation for thyroid lobectomy may be modified based on clinical or sonographic characteristics and/or molecular testing (Strong recommendation, Moderate-quality evidence).

  Recommendation 20 states that total thyroidectomy may be preferred in patients with indeterminate nodules which are positive for known mutations specific for carcinoma (Strong recommendation, Moderate-quality evidence).

The National Comprehensive Cancer Network (NCCN) Guidelines

The National Comprehensive Cancer Network NCCN guidelines (Version I.2016) (www.nccn.org) provide recommendations for use of molecular testing in indeterminate cytology nodules to select observation over surgery and for selecting the extent of surgery.

— The NCCN guidelines state that for thyroid nodules evaluated with FNA, with a cytologic diagnosis of AUS/FLUS (Bethesda III) and Follicular or Hurthle cell neoplasms (Bethesda IV) molecular diagnostics may be employed (category B recommendation).

— If molecular testing, in conjunction with clinical and ultrasound features, predicts a risk of malignancy comparable to the risk of malignancy seen in a benign FNA cytology (approximately 5% or less), consider observation.

— If molecular testing suggests papillary thyroid carcinoma, especially in the case of BRAF V600E mutation, apply the same management as for papillary carcinoma.

Cibas ES, Ali SZ. The 2017 Bethesda System for Reporting Thyroid Cytopathology. Thyroid. 2017