Clinical challenges with calcitonin-negative medullary thyroid carcinoma

Medullary thyroid carcinoma (MTC) is a relatively uncommon malignant tumor of the parafollicular C cells of the thyroid, which distinguishing feature is the production of calcitonin (CT). CT is a well-recognized tool in the diagnosis and the postsurgical follow-up of patients with MTC with a high sensitivity and specificity, and represents a powerful prognostic indicator. Usually, there is a direct correlation between tumor size and basal CT levels. However, few cases of CT-negative MTCs have been reported in literature and criteria for diagnosis and follow-up are still controversial. We performed a brief review on CT-negative MTC and reported our experience on this rare condition, focusing on the clinical characteristics at presentation, the histological and immunostaining features, and the management. Fifteen cases of large, palpable, CT-negative MTCs have been reported in the literature so far; moreover, we reported four cases followed at our center. Although CT-negative MTC is rare, normal/low serum levels of CT and CEA cannot completely exclude the possibility of the diagnosis, when suspected. It is well accepted that early diagnosis is crucial, but there is still no consensus on the optimal postoperative surveillance strategy. The ultrasound evaluation of the cervical region, together with abdominal computerized tomography scan, chest X-ray, and fluorine18-fluorodeoxyglucose (F-18-FDG) PET/computed tomography (FDG-PET/CT), would be recommended in the follow-up of such cases.