Thyroglobulin in fine-needle aspiration wash-out diagnostic performance: a meta-analysis

Introduction: Differentiated thyroid cancer (DTC) has an excellent prognosis. However, DTC frequently metastasizes to cervical lymph nodes (CLN). In case of suspicious ultrasonography findings, the fine-needle aspiration (FNA) is usually required to confirm or exclude metastasis. The combination of FNA-cytology and thyroglobulin (Tg) measurements in the needle washout has been reported to increase the sensitivity of FNA in identifying lymph node metastases from DTC, particularly in the case of very small CLN. This assay is recommended by the revised American Thyroid Association guidelines for the follow-up of patients with DTC. Methods: We have selected, through electronic databases, 28 original studies, published from 1992 through 2012. Each study deals with a small number of patients and is likely affected by selection bias. Pooled sensitivity, specificity, likelihood ratios (LR) and diagnostic odds ratio (dOR) were calculated. Results: Including in the analysis all the studies with complete data (17 studies), the pooled sensitivity is 95.8% (95% CI 94.3–97%), specificity 91.5% (95% CI 89.1–93.5%), positive LR 15.33 (95% CI 6.97–33.70), and negative LR 0.06 (95% CI 0.04–0.11). However, there is a significant heterogeneity between studies, not due to threshold effect (Spearman correlation coefficient −0.146; P=0.52). A meta-regression analysis demonstrated that the presence or absence of thyroid gland (evaluation before thyroidectomy or during after-surgery follow-up) is an important heterogeneity factor (rdOR 4.57; 95% CI 1.34–15.61; P=0.02). Including only studies reporting data from patients during follow-up (ten studies), the pooled sensitivity is 98.7% (95% CI 96.8–99.7%), specificity 97.9% (95% CI 95.2–99.3%), positive LR 17.47 (95% CI 7.81–39.10), and negative LR 0.04 (95% CI 0.02–0.09). Conclusion: FNA-Tg measurement is a very accurate tool to detect CLN metastases from DTC. However, a better standardization of criteria for patient selection, analytical methods and threshold levels is required to provide useful data and to improve management of DTC patients.