Whether molecular testing adds diagnostic value to the evaluation of thyroid nodules 4-cm or larger is unknown. The impact of molecular testing on cytopathologic-histopathologic diagnosis of neoplasm (adenoma or malignant), stratified by nodule size <or≥ 4-cm, was analyzed from a surgical series. Of 490 index nodules, molecular testing was performed on 18% of 353 nodules <4-cm and 8.8% of 137 nodules ≥4-cm (p = 0.0118). Adenoma was higher (30% vs 14%) and malignancy lower in nodules ≥4-cm vs <4-cm (p < 0.0001). Molecular testing impacted the finding of malignancy in the <4-cm group. Molecular testing of the ≥4-cm AUS and FN cytology subcategory impacted neoplasm discovery (combining adenoma and malignancy), with mutation positive 100% (3/3), mutation negative 38% (3/8), no mutation testing 88% (21/24), p = 0.0122. In conclusion, more adenoma was found in nodules ≥4-cm, including those with benign cytology, which was not explained by available molecular testing results. Molecular testing impacted the finding of malignancy in thyroid nodules <4-cm. The overall number of ≥4-cm nodules with molecular testing in this study was too low to exclude its diagnostic value in this setting. Further study is recommended to include molecular testing in nodules ≥4-cm, including those with benign cytology, to identify follicular adenoma.
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