Diagnostic Utility of Molecular and Imaging Biomarkers in Cytological Indeterminate Thyroid Nodules

Author:

de Koster Elizabeth J1,de Geus-Oei Lioe-Fee2,Dekkers Olaf M34,van Engen-van Grunsven Ilse5,Hamming Jaap6,Corssmit Eleonora P M3,Morreau Hans7,Schepers Abbey6,Smit Jan8,Oyen Wim J G19,Vriens Dennis2

Affiliation:

1. Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands

2. Department of Radiology, Section of Nuclear Medicine, Leiden University Medical Center, Leiden, the Netherlands

3. Department of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands

4. Department of Epidemiology, Leiden University Medical Center, Leiden, the Netherlands

5. Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands

6. Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands

7. Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands

8. Department of Endocrinology, Radboud University Medical Center, Nijmegen, the Netherlands

9. Division of Radiotherapy and Imaging, Institute of Cancer Research, and Department of Nuclear Medicine, Royal Marsden Hospital, London, United Kingdom

Abstract

Abstract Indeterminate thyroid cytology (Bethesda III and IV) corresponds to follicular-patterned benign and malignant lesions, which are particularly difficult to differentiate on cytology alone. As ~25% of these nodules harbor malignancy, diagnostic hemithyroidectomy is still custom. However, advanced preoperative diagnostics are rapidly evolving. This review provides an overview of additional molecular and imaging diagnostics for indeterminate thyroid nodules in a preoperative clinical setting, including considerations regarding cost-effectiveness, availability, and feasibility of combining techniques. Addressed diagnostics include gene mutation analysis, microRNA, immunocytochemistry, ultrasonography, elastosonography, computed tomography, sestamibi scintigraphy, [18F]-2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), and diffusion-weighted magnetic resonance imaging. The best rule-out tests for malignancy were the Afirma® gene expression classifier and FDG-PET. The most accurate rule-in test was sole BRAF mutation analysis. No diagnostic had both near-perfect sensitivity and specificity, and estimated cost-effectiveness. Molecular techniques are rapidly advancing. However, given the currently available techniques, a multimodality stepwise approach likely offers the most accurate diagnosis, sequentially applying one sensitive rule-out test and one specific rule-in test. Geographical variations in cytology (e.g., Hürthle cell neoplasms) and tumor genetics strongly influence local test performance and clinical utility. Multidisciplinary collaboration and implementation studies can aid the local decision for one or more eligible diagnostics.

Funder

Dutch Cancer Society

Publisher

The Endocrine Society

Subject

Endocrinology,Endocrinology, Diabetes and Metabolism

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