Impact of Mutational Testing on the Diagnosis and Management of Patients with Cytologically Indeterminate Thyroid Nodules: A Prospective Analysis of 1056 FNA Samples

Abstract

Molecular analysis for a panel of mutations has significant diagnostic value for all categories of indeterminate cytology and can be helpful for more effective clinical management of these patients.

Molecular markers in the diagnosis of thyroid nodules

“…Malignant thyroid nodules with indeterminate Bethesda categories III and IV cytology have a low incidence of BRAF mutation (37,38). This is not unexpected as these thyroid nodule categories include malignant tumors that less commonly (or never) harbor BRAF mutations such as follicular thyroid cancer, Hürthle cell thyroid cancer, follicular variant PTC, and medullary thyroid cancer.…”

“…However, the low incidence is also explained by the finding that BRAF mutated PTCs have cytological features that cytopathologists recognize and classify as suspicious for malignancy or malignant (Bethesda categories V and VI); cytological categories typically treated with total thyroidectomy regardless of BRAF status (37). Conversely, PTCs with indeterminate cytology are more often BRAF negative (37,38).…”

“…A review of four studies combining all four mutation--markers into a single panel had 64% sensitivity, thus failing to identify 36% of thyroid cancers (39). The largest study of mutational markers was a retrospective analysis of prospectively collected samples where the mutational status was available to the clinicians, including the histopathologist (38). The mutational marker NPV for Bethesda categories IV and V were 86% and 72%, respectively.…”

“…High PPV tests with inadequate NPV performance can "rule in" cancer and perhaps alter the extent of surgery, but they cannot "rule out" cancer, so surgery cannot be avoided. Currently, the strongest argument for their use is where the decision has been made for surgery, but the extent of surgery may be determined by the test result (38,40). Based on the potential ability to prevent completion thyroidectomies by performing an initial total thyroidectomy in patients with indeterminate cytology when a DNA mutation is present, Yip and cols.…”

Annual Financial Impact of Thyroidectomies for Nodular Thyroid Disease in China

“…This is true especially when thyroid FNA results turn out to be indeterminate. When a nodule is indeterminate by FNA, the optimal way is to repeat FNA or undergo molecular tests (Alexander, 2008;Nikiforov et al, 2009;Nikiforov et al, 2011;Alexander et al, 2012;Kim and Alexander, 2012;Zhou et al, 2012;Nikiforov et al, 2013;Ranjbari et al, 2013;Alexander et al, 2014). Surgery, however, should be regarded as the last resort if all the other options still fail to produce satisfactory results.…”