Comparison of pre-operative calcitonin, FNAC, and ultrasound risk stratification systems in patients with medullary thyroid carcinoma

Context: Although the diagnostic performance of calcitonin (CTN) in revealing medullary thyroid carcinoma (MTC) has been widely demonstrated, to date, neck ultrasound (neck US) and FNAC remain the first-line tools in searching for malignancy in thyroid nodules. Objective: This study aims to determine which tool is more effective at suggesting MTC among preoperative CTN values and FNAC, compared with the estimated risk of malignancy at neck US according to the 5 main risk stratification systems (RSS), in a population of patients with already diagnosed MTC. Methods: We evaluated preoperative serum CTN, FNAC, and neck US data in 104 patients with sporadic MTC (2014–2020) managed at the Unit of Endocrinology of the Pisa University Hospital, Italy. Results: According to the neck US RSS, 59.6% of patients were classified as the intermediate-low suspicion (ILS) and 40.4% as the high suspicion (HS) group. FNAC, performed according to clinical judgment in 85/104 (81.7%) cases, was diagnostic of MTC in only 45.9% of cases. Moreover, according to the guidelines, 39 (62.9%) nodules in the ILS and 14 (33.3%) in the HS group would not even be submitted for FNAC. Of note, most of these MTCs had tumor dimensions > 1 cm and/or lymph node metastases. Conversely, the preoperative CTN values suggested at least a suspicion of MTC in both US risk groups and across all MTC US dimension categories, including microcarcinomas. Conclusions: Among patients with a confirmed diagnosis of MTC, serum CTN values were the most reliable parameter, outperforming ultrasound features and FNAC in diagnostic accuracy. Delaying or failing to diagnose MTC is undesirable if the aim is to achieve early diagnosis and effective treatment of these patients.