Update on the cytologic and molecular features of medullary thyroid carcinoma

Medullary thyroid carcinoma (MTC) accounts for only 5% to 10% of all thyroid carcinomas, but it is the most aggressive form of well-differentiated thyroid carcinoma, being responsible for 8% to 15% of all thyroid cancer-related deaths. MTC is frequently diagnosed at a locally advanced or metastatic stage, and 10-year survival rates in these cases are <20%. Fine-needle aspiration biopsy of the thyroid gland is an accurate method to diagnose MTC, having a high sensitivity and specificity. The cytologic features of MTC are characteristic and the cytologic diagnosis of classic MTC is often straightforward, especially when combined with immunocytochemistry. However, because of its morphologic heterogeneity and overlap with other tumors, the differential diagnosis of MTC on cytology and on histology is broad with several potential pitfalls. Significant advances have been made over the last decade in understanding MTC. This concerns mainly the early detection of MTC, especially in familial forms (eg, multiple endocrine neoplasia type 2), and the identification of key molecular pathways and alterations which now offer promising targets for specific therapies in progressive MTC cases. Genetic testing (eg, RET mutation) has allowed for early detection in asymptomatic carriers and high-risk patients, with prophylactic thyroidectomy often being curative. Targeted therapies with multityrosine-kinase inhibitors (eg, vandetanib or cabozantinib) have emerged as promising new treatments for recurrent or metastatic MTC. In this review article, we discuss the cytologic features of MTC and its variants, its differential diagnosis, the role of ancillary studies, and the salient molecular features of MTC.