Introduction: Persistent or recurrent cervical lymph node metastases represent a frequent challenge during follow-up of differentiated thyroid carcinoma. Although fine-needle aspiration cytology (FNAC) and thyroglobulin measurement in FNA washout (FNA-Tg) are standard diagnostic tools, their performance may be limited in cystic or paucicellular lymph nodes and in patients with residual thyroid tissue or anti-thyroglobulin antibodies. Measurement of cytokeratin 19 fragment 21-1 (CYFRA 21-1) in FNA washout has been proposed as a complementary biomarker.
Methods: A systematic review and diagnostic test accuracy meta-analysis was conducted according to PRISMA-DTA guidelines and registered in PROSPERO. PubMed, Scopus, and Cochrane Central were searched through January 2026. Pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio were estimated using a bivariate random-effects model with hierarchical summary receiver operating characteristic analysis.
Results: Five studies comprising 533 patients and 681 lymph nodes were included. CYFRA 21-1 showed high pooled sensitivity (0.92, 95% CI: 0.85-0.96) and specificity (0.97, 95% CI: 0.89-0.99), with an area under the curve of 0.97. The diagnostic odds ratio was 173.1, and likelihood ratios suggested good rule-in and rule-out performance. Qualitative comparisons indicated that CYFRA 21-1 frequently show higher sensitivity than FNAC and comparable or higher specificity than FNA-Tg in selected challenging scenarios.
Conclusions: CYFRA 21-1 measurement in FNA washout shows promising diagnostic performance and may provide complementary information to cytology and thyroglobulin washout. However, the available evidence is limited and heterogeneous, and further prospective, multicenter studies with standardized protocols are required before routine clinical implementation can be recommended.
Keywords: CYFRA 21-1; Cytology; Differentiated thyroid carcinoma; Fine-needle aspiration; Thyroglobulin.
© 2026 S. Karger AG, Basel.