title: Molecular profiling of thyroid nodule fine-needle aspiration cytology.
abstract: 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.
authors.affiliation: Department of Oncology, Cumming School of Medicine, University of Calgary, Tom Baker Cancer Centre, 1331 - 29th Street NW, Calgary, Alberta T2N 4N2, Canada.|Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Health Research Innovation Centre, 3280 Hospital Drive, Calgary, Alberta T2T 4Z6, Canada.
authors.forename: Markus
authors.initials: M
authors.lastname: Eszlinger
authors.affiliation: Division of Endocrinology, Department of Medicine, Cumming School of Medicine, University of Calgary, Richmond Road Diagnostic and Treatment Centre, 1820 Richmond Road SW, Calgary, Alberta T2T 5C7, Canada.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Lau
authors.affiliation: Division of Endocrinology, Department of Medicine, Cumming School of Medicine, University of Calgary, Richmond Road Diagnostic and Treatment Centre, 1820 Richmond Road SW, Calgary, Alberta T2T 5C7, Canada.
authors.forename: Sana
authors.initials: S
authors.lastname: Ghaznavi
authors.affiliation: Division of Endocrinology, Department of Medicine, Cumming School of Medicine, University of Calgary, Richmond Road Diagnostic and Treatment Centre, 1820 Richmond Road SW, Calgary, Alberta T2T 5C7, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Symonds
authors.affiliation: Department of Oncology, Cumming School of Medicine, University of Calgary, Tom Baker Cancer Centre, 1331 - 29th Street NW, Calgary, Alberta T2N 4N2, Canada.|Department of Surgery, Cumming School of Medicine, University of Calgary, Foothills Medical Centre, North Tower 1012, 1403 - 29th Street NW, Calgary, Alberta T2N 2T9, Canada.
authors.forename: Shamir P
authors.initials: SP
authors.lastname: Chandarana
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Centre, McCaig Tower, 1403 - 29th Street NW, Calgary, Alberta T2N 2T9, Canada.
authors.forename: Moosa
authors.initials: M
authors.lastname: Khalil
authors.affiliation: Department of Oncology, Cumming School of Medicine, University of Calgary, Tom Baker Cancer Centre, 1331 - 29th Street NW, Calgary, Alberta T2N 4N2, Canada.|Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Health Research Innovation Centre, 3280 Hospital Drive, Calgary, Alberta T2T 4Z6, Canada.|Division of Endocrinology, Department of Medicine, Cumming School of Medicine, University of Calgary, Richmond Road Diagnostic and Treatment Centre, 1820 Richmond Road SW, Calgary, Alberta T2T 5C7, Canada.|Department of Medicine, Cumming School of Medicine, University of Calgary, North Tower 9th floor, 1403 - 29th Street NW, Calgary, Alberta T2N 2T9, Canada.|Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Health Research Innovation Centre, 3280 Hospital Drive, Calgary, Alberta T2N 4Z6, Canada.
authors.forename: Ralf
authors.initials: R
authors.lastname: Paschke
mesh_terms: D044963:Biopsy, Fine-Needle / Q000379:methods*; D006801:Humans; D057089:Pathology, Molecular / Q000295:instrumentation* / Q000379:methods*; D016606:Thyroid Nodule / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology