Medullary thyroid carcinoma (MTC) was recognized in the 1950s by Hazard et al.49 as a distinct clinicopathologic entity. Over the next 10 years, investigators identified and described the parafollicular C cell that produces calcitonin and give rise to MTC. During the decade of the 1970s, Wells et al.50 extended the measurement of calcitonin by defining a provocative test that rendered this hormonal tumor marker one of the most sensitive and specific in all of oncology. Understanding of the familial associations of MTC with corollary genetic studies reported in the 1980s and early 1990s have defined molecular changes responsible for familial forms of inherited MTC and with implications for sporadic MTC as well. The familial forms of MTC are outlined in Table 108.4. More recent research has identified genotype–phenotype relationships and has led to more individualized treatment of patients with inherited MTC.51 For details on molecular pathogenesis of MTC see Chapter 107.

MTC constitutes between 3% to 12% of most institutional series of detectible thyroid cancers.23 As opposed to well-differentiated thyroid cancer, MTC is not associated with radiation exposure, but it does occur in distinct familial syndromes. Sporadic or nonfamilial MTC accounts for 60% to 70% of cases, with three distinct familial syndromes accounting for the remainder. MTC is the most prominent clinical diagnosis in multiple endocrine neoplasia (MEN)-2A and MEN-2B. In 1986, familial MTC in the absence of the associated features of MEN-2A or MEN-2B ...