Fine needle aspiration cytology and fine-needle aspirate calcitonin for diagnosing medullary thyroid carcinoma:a systematic review and meta-analysis

ObjectiveTo systematically evaluate the diagnostic value of fine-needle aspiration cytology (FNAC) and fine-needle aspiration washout calcitonin (FNA-CT) in medullary thyroid carcinoma (MTC).MethodsPublished studies on FNAC and FNA-CT for the diagnosis of MTC wereretrieved from Chinese and English databases from January 1, 1995 to December31, 2024. The quality of the included studies was assessed using the QUADAS-2tool. Meta-analysis was performed using Stata 16.0. Pooled sensitivity, specificity,positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio werecalculated. Forest plots and summary receiver operating characteristic (SROC)curves were generated, and the area under the curve (AUC) was calculated toassess diagnostic performance. Spearman correlation analysis was used to assessthe threshold effect. Heterogeneity was evaluated using Cochran's Q test and the I²statistic, and either a fixed-effects model or a random-effects model was selectedaccordingly. Meta-regression analysis was further performed to explore potentialsources of heterogeneity. Deeks' funnel plot was used to assess publication bias,and Fagan plots together with likelihood ratio scattergrams were used to evaluateclinical utility.ResultsA total of 13 studies involving 937 patients with 444 MTC lesions were finally included in the analysis. For FNAC, the pooled sensitivity, specificity, positive likelihoodratio, negative likelihood ratio, and diagnostic odds ratio were 0.56 (95% CI: 0.51-0.61), 0.98 (95% CI: 0.94-1.00), 34.25 (95% CI: 8.98-130.62), 0.45 (95% CI: 0.39-0.51),and 76.97 (95% CI: 18.72-316.52), respectively. For FNA-CT, the correspondingvalues were 0.98 (95% CI: 0.94-0.99), 0.97 (95% CI: 0.94-0.99), 37.42 (95% CI: 16.91-82.80), 0.02 (95% CI: 0.01-0.06), and 1891.55 (95% CI: 351.09-10191.13), respectively. The AUCs of FNAC and FNA-CT for diagnosing MTC were 0.65 and 1.00, respectively. Meta-regression analysis suggested that the heterogeneity ofFNAC might be related to sample size and detection method, whereas nosignificant source of heterogeneity was identified for FNA-CT. Possible publicationbias was detected in both methods. Fagan plot analysis showed that, at a pretestprobability of 20%, FNA-CT had high clinical utility for both confirming andexcluding MTC. Likelihood ratio scattergram analysis showed that FNA-CT had highclinical value for both confirming and excluding MTC, whereas FNAC had goodvalue for confirming MTC but limited value for excluding it.ConclusionFNA-CT demonstrates high diagnostic value for MTC, with overall diagnostic efficacy superior to that of FNAC, suggesting it holds promise as an important auxiliary method for the preoperative diagnosis of MTC.