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The differential diagnosis and malignancy risk stratification of thyroid nodules requires multidisciplinary expertise and knowledge of both local ultrasonography practices and the local malignancy rates for a given fine-needle aspiration (FNA) result. Even in such a multidisciplinary setting, FNA cytology has the inherent limitation that indeterminate cytology results cannot distinguish between follicular adenomas, follicular thyroid carcinomas or follicular variant papillary thyroid carcinomas. Accumulating evidence suggests that this limitation can be overcome by using molecular diagnostic approaches. In this Review, we present the advantages and disadvantages of the different molecular diagnostic methodologies, which can be divided into two approaches: those that 'rule out' malignancy (to reduce the overtreatment of benign nodules) and those that 'rule in' malignancy (to optimize surgical planning). We identify microRNA classifiers as potential additional markers for use in a two-step diagnostic approach, consider the potential implications of the reclassification of noninvasive encapsulated follicular variant papillary thyroid carcinomas to noninvasive follicular thyroid neoplasms with papillary-like nuclear features and discuss the cost-effectiveness of molecular testing. Molecular FNA diagnostics is an important complementary addition to FNA cytology that could substantially reduce unnecessary surgery and better define the need for appropriate surgery in patients who have thyroid nodules with indeterminate FNA cytology.

Liquid-based cytology and cell block specimens are equally important in maximizing the diagnostic yield in EBUS-guided and conventional TBNA in suspected sarcoidosis. Good interobserver agreement between cytopathologists was noted, with improved diagnostic yield after review by a pulmonary cytopathologist. None of the clinical factors assessed impacted on the diagnostic yield of the procedure on a per-node basis.

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To determine accuracy and intertest agreement of preoperative fine-needle aspiration cytology (FNAC) and intraoperative frozen-section analysis (FS) findings in thyroid surgery, and to assess the influence of intraoperative FS findings on decision making and the utility of FS in thyroid surgery. Design: Retrospective analysis. The results of preoperative FNAC, intraoperative FS, and final histopathological analyses were taken from the histopathology reports. We calculated intertest agreement using the statistic. Patients: Two-hundred fifteen patients who underwent primary thyroid surgery. All patients were treated by the same surgeon (S.J.W.). Results: The sensitivity and specificity of FNAC were 57.4% and 91.7%, respectively. The sensitivity and specificity of FS were 32.4% and 96.5%, respectively. The intertest agreement was poor (=0.17). In case of malignant FNAC findings, the FS result did not influence treatment decisions; in case of a malignant FS result on the background of a benign, indeterminate, or nondiagnostic FNAC finding, the FS result influenced treatment decisions in 88% of cases. Conclusions: Intraoperative FS did not give additional information in cases where a malignant neoplasm was predicted by the FNAC finding. In this setting, it led to conflicting results and did not contribute to correct decision making.

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