498 chapter 13 “[A20] What is the utility of [18F]FDG-PET scanning to predict malignant or benign disease when fine needle aspiration cytology (FNAC) is indeterminate? Recommendation 18: [18F]FDG-PET imaging is not routinely recommended for the evaluation of thyroid nodules with indeterminate cytology [Weak recommendation, Moderate-quality evidence]” [17]. In contrast, a positive recommendation was made for MD to aid the malignancy risk assessment before proceeding to diagnostic surgery (Bethesda III or IV) or active surveillance (Bethesda III) and after consideration of suspicious clinical and ultrasonographic features (Bethesda III and IV) and/or repeating the FNAC (Bethesda III). “Recommendation 15 [A] For nodules with AUS/FLUS cytology, after consideration of worrisome clinical and sonographic features, investigations such as repeat FNA or molecular testing may be used to supplement malignancy risk assessment in lieu of proceeding directly with a strategy of either surveillance or diagnostic surgery. Informed patient preference and feasibility should be considered in clinical decision-making. [Weak recommendation, Moderate-quality evidence]” and “Recommendation 16 [A] Diagnostic surgical excision is the long-established standard of care for the management of FN/SFN cytology nodules. However, after consideration of clinical and sonographic features, molecular testing may be used to supplement malignancy risk assessment data in lieu of proceeding directly with surgery. Informed patient preference and feasibility should be considered in clinical decision-making. [Weak recommendation, Moderate-quality evidence]” [17]. These cautious recommendations were made in the time when MD as a preoperative diagnostic for indeterminate thyroid nodules was still in its infancy, when the key publications of the earlier versions of the commercial molecular tests (i.e., the Afirma® GEC and miRInform thyroid test, precursors of the Afirma® GSC and ThyroSeq, respectively) were admittedly well-received, but clinical validation studies were still in progress [69, 164]. But that was almost a decade ago. Today, these national and international guidelines appear outdated. Our understanding of the molecular biology of thyroid neoplasms as well as techniques for molecular testing and molecular imaging have greatly advanced over the past years [692, 694]. Molecular panels have increasingly become more extensive, including a greater diversity of molecular alterations in mysterious diagnostic algorithms, resulting in higher NPVs as well as PPVs [490, 491, 683, 693, 696]. The progression from standalone PET to combined PET/CT imaging and the increasing spatial resolution have respectively improved the anatomical correlation and precision of [18F]FDG-PET/CT
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