Medullary Thyroid Carcinoma

Medullary thyroid carcinoma (MTC) is a rare calcitonin (Ctn)-secreting tumour of the C cells of the thyroid. MTC often have the clinical and histological features of neuroendocrine tumours. They account for 3–5% of all thyroid carcinomas and occur in both sporadic (70%) and hereditary forms (30%). The familial variety of MTC is inherited as an autosomal dominant trait with a high degree of penetrance and is associated with multiple endocrine neoplasia type 2 syndrome. It is caused by germline-activating mutations of the RET proto-oncogene. Detection of MTC in patients has changed in recent years with the introduction of specific strategies: Ctn screening in patients with thyroid nodules and screening with molecular methods for RET proto-oncogene mutations in patients with apparently sporadic MTC and in family members at risk for MTC. By earlier identification of patients with MTC, the presentation has changed from clinical tumours to preclinical disease, resulting in a high cure rate of affected patients with much better prognosis. Surgery represents the only curative therapeutic strategy; the definitive treatment is a total thyroidectomy and, if necessary, central and lateral lymph node dissection. Tumour staging, either postoperatively or by imaging, and measuring the tumour markers Ctn and carcinoembryonic antigen (CEA), allows for the use of a dynamic risk-adapted stratification of follow-up procedures. In advanced metastatic MTC, molecular targeted therapy using tyrosine kinase receptor inhibitors helps controlling tumour progression and prolongs progression-free survival. The outcome for most MTC patients is excellent compared to those with other cancers.