editorials December 01, 2018 December 01, 2018

Critical analysis of molecular tests in indeterminate thyroid nodules

DOI: 10.20945/2359-3997000000095

WHICH TEST SHOULD BE CHOSEN?

Only a few institutions reported their experience and compared the performance of molecular tests in similar conditions. In one of them, two-thirds of Bethesda categories III and IV lesions were managed nonoperatively based on nonsuspicious results of Thyroseq^® v2 or Afirma^® GEC. Considering the rate of malignancy of 14%, Livhits and cols. () demonstrated that ThyroSeq^® v.2 had a better performance to identify malignancy compared to GEC (PPV 57% vs. 39%). Similarly, Jug and cols. demonstrated that “negative” results in molecular tests helped to reduce surgery indication in ~50% of patients (). Considering the rate of malignancy of only 12%, ThyroSeq^® v.2 had PPV of 40% and 50% in Bethesda categories III and IV and GEC had PPV of 29% in Bethesda category III and 27% in Bethesda category IV. Therefore, the performance of the molecular tests must be carefully interpreted, considering that different populations, diverse prevalence of malignancy, and the fact that not all patients were submitted to confirmatory surgery altogether, interfere in results when compared to clinical validation studies. While microRNA panels have limited multicenter experience, we could suggest that both Afirma^® GEC/GSC and ThyroSeq^® v2/v3 might be used to improve preoperative diagnosis of Bethesda categories III and IV lesions. High cost and no health insurance coverage limit the widespread application of molecular tests in Brazil and other countries.

It is always important to consider risk factors, patient´s clinical conditions and desire, and, certainly, US characteristics before choosing a molecular test. We usually wish to identify benign lesions in order to defer diagnostic surgeries. High-risk nodules at US may not benefit from “rule-out” molecular test to avoid surgery. Actually, in high-risk nodules, a “positive” result in a “rule-in” test, reinforcing malignancy, is more useful, as a partial diagnostic surgery may turn into total thyroidectomy to treat cancer. On the other hand, if we evaluate an indeterminate or low-risk nodule at US, “rule-out” tests seem more relevant because of their low rate of false-benign results.

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