Researchers recently revised the clinicopathological features of calcitonin (Ct)-negative medullary thyroid carcinoma (MTC) cases to share strategies for improving their clinical management since these cases are extremely rare and difficult to diagnose.

“The diagnosis of Ct-negative MTC patients should be based mainly on imaging methods and clinical judgements,” Jingzhu et al said in a study published in the journal Annals of The Royal College of Surgeons of England.

Hence, methods such as ultrasonography and computed tomography are important to the establishment of the diagnosis.

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In addition, new methods have been suggested by some authors, including measuring the levels of Ct in aspiration needle washout fluids calcium stimulation of Ct, and following up on Ct and carcinoembryonic antigen (CEA) levels.

Increased levels of Ct and CEA have been reported in some cases of recurrent Ct-negative MTC cases. However, Jingzhu et al found normal Ct levels during disease progression in patients from their centre. The use of CEA as an alternative marker in Ct-negative MTC is still controversial.

There are also promising biomarkers, including procalcitonin, chromogranin A, and synaptophysin, which have already been used in clinical practice.

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Current guidelines recommend complete surgical resection and radical lymph node dissection as a treatment for Ct-negative MTC. However, postoperative follow-up can be challenging since routine imaging methods usually fail to detect small lesions.

The researchers found 39 Ct-negative MTC cases reported in the literature. In addition, they combined data from 3 patients diagnosed at their centre (out of a series of 153 patients with MTC).


Jingzhu Z, Xiangqian Z, Ming G, et al. Clinical challenges with calcitonin-negative medullary thyroid carcinoma: three case reports and a review of the literature. Ann R Coll Surg Engl. Published online November 12, 2021. doi:10.1308/rcsann.2020.7118