Medullary Thyroid Carcinoma

Abstract

Medullary thyroid carcinoma (MTC) comprises approximately 1-2% of thyroid malignancies. MTC occurs in both sporadic and heritable forms. Hereditary forms account for up to 25% of MTC and include Multiple Endocrine Neoplasia (MEN) types 2A and 2B, with germline RET proto-oncogene gain-of-function mutations, or hereditary isolated MTC (formerly familial medullary thyroid carcinoma). Most cases of MTC demonstrate characteristic cytomorphology and a distinctive immunophenotype, but MTC can show a wide variety of growth patterns, cell shapes, and nuclear and cytoplasmic features. This morphologic heterogeneity leads to significant diagnostic challenges in the cytologic and histologic evaluation of this neoplasm. Characteristic features include a dispersed non-cohesive cell pattern, plasmacytoid and/or spindled cell shapes, finely granular chromatin, inconspicuous nucleoli, intranuclear pseudoinclusions, cytoplasmic granularity, and amyloid. Immunocytochemistry is helpful for distinguishing MTC from its cytologic mimics. Additional ancillary tests include measurement of calcitonin levels in needle washout fluid from FNA of thyroid nodules, thyroidectomy beds, and/or lymph nodes, particularly in patients with elevated serum calcitonin levels and/or with FNA findings that are inconclusive for MTC. Molecular testing is also of value. Surgical treatment is usually total thyroidectomy and central lymph node dissection, with consideration of lateral cervical lymph node dissection depending on imaging studies and serum calcitonin levels.