Optimizing Diagnostic Accuracy of Fine Needle Aspiration Biopsy Calcitonin Measurements in Detecting Medullary Thyroid Carcinoma

Optimizing Diagnostic Accuracy of Fine Needle Aspiration Biopsy Calcitonin Measurements in Detecting Medullary Thyroid Carcinoma

Dr. Andrea CAMILA Cavallo, Dr. Fabián Pitoia, Dr. Javier Roberti, Dr. Pablo Brenzoni, Dr. Melisa Lencioni, Dr. Maria Jose Jaroslavsky, Dr. Eunice Spengler, Dr. Ana Voogd, Dr. Claudia Firpo, Dr. Pedro Saco, Dr. Federico Piñero, and Dr. Maria Negueruela

Abstract

Background: The optimal cutoff value of calcitonin (Ctn) levels measured using an electrochemiluminescence immunoassay (ECLIA) obtained from the washout fluid of fine-needle aspiration (FNA-Ctn) for the diagnosis of medullary thyroid carcinoma (MTC) is currently not established. We evaluated the diagnostic accuracy and clinical utility of FNA-Ctn for the diagnosis and location of MTC in patients with nodular or multinodular goiters. Methods: This was a case-control study nested on a prospective multicenter cohort of patients with nodular or multinodular goiter, normal or elevated serum Ctn, and thyroidectomy indications. Ctn and FNA-Ctn were measured using ECLIA methodology before surgery. From this nested cohort, MTC cases and controls (non-medullary pathology) were identified from the final pathological analysis. Cumulative incidence sampling of controls was randomly performed at a 1:2 ratio. Sensitivity, specificity, and area under the receiver operator curve (AUROC) were calculated for patients and the total number of thyroid nodules. Results: From 1272 patients included in the prospective cohort, 50 MTC cases and 105 controls were included. In this study, 286 thyroid nodules were evaluated (63 MTC and 223 non-MTCs). Median serum Ct was significantly higher in cases [525 pg/mL (IQR, 162.5 – 1.200)] than in controls [1.6 pg/mL (0.5 – 5.6); P<.001]. The median FNA-Ctn was significantly higher in MTC nodules [3.100 pg/mL (IQR, 450 – 45200)] than in non-MTC nodules [0.5 pg/mL (IQR, 0.5 – 0.5), P<0.0001]. In 11 MTC patients with multinodular goiter, FNA-Ctn was significantly higher in non-medullary nodules located in the same lobe where an MTC nodule was diagnosed (P=0.0002). Overall, the FNA-Ctn AUROC was 0.99 (95% CI 0.98–1.0), and a threshold of ≥220 pg/mL showed 100% sensitivity and 98% specificity for MTC diagnosis. Conclusions: The use of FNA-Ctn measured by ECLIA showed adequate diagnostic accuracy for MTC diagnosis. Moreover, it may be clinically useful for localization in multinodular goiter when lobectomy is considered.

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