Thyroid Nodule Diagnostic Markers in the Face of the New NIFTP Category: Time for a Reset?

Background: Current thyroid molecular tests are specifically designed for the differential diagnosis of nodules with indeterminate or suspicious fine-needle aspiration (FNA) cytology. Summary: However, their clinical validity faces challenges from both variation among institutions in cancer prevalence and, most recently, the new category of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The latter diagnosis was previously classified as malignant. Relevant to this, all molecular panels on the market today were originally tested and validated within the context of these entities being considered malignant. Conclusion: This review examines possible effects of the NIFTP reclassification as a precancerous lesion on the original validation studies and, investigates the effect of the significant reported variability in thyroid cancer prevalence on the performance of these tests.