Table 3. Percentage of Patients with Clinical Features of MEN2 by Subtype continued...
MTC accounts for 2% to 3% of new cases of thyroid cancer diagnosed annually in the United States, although this figure may be an underrepresentation of true incidence because of changes in diagnostic techniques. The total number of new cases of MTC diagnosed annually in the United States is between 1,000 and 1,200, about 75% of which are sporadic (i.e., they occur in the absence of a family history of either MTC or other endocrine abnormalities seen in MEN2). The peak incidence of the sporadic form is in the fifth and sixth decades of life.[2,17] A study in the United Kingdom estimated the incidence of MTC at 20 to 25 new cases per year among a population of 55 million.
In the absence of a positive family history, MEN2 may be suspected when MTC occurs at an early age or is bilateral or multifocal. While small series of apparently sporadic MTC cases have suggested a higher prevalence of germline RET mutations,[18,19] larger series indicate a prevalence range of 1% to 7%.[20,21] Based on these data, it is widely recommended that RETgene mutation testing be performed for all cases of MTC.[22,23,24,25]
Level of evidence (Screening): 3
Natural history of MTC
Thyroid cancer represents approximately 3% of new malignancies occurring annually in the United States, with an estimated 60,220 cancer diagnoses and 1,850 cancer deaths per year. Of these cancer diagnoses, 2% to 3% are MTC.[16,27]
MTC arises from the parafollicular calcitonin-secreting cells of the thyroid gland. MTC occurs in sporadic and familial forms and may be preceded by CCH, although CCH is a relatively common abnormality in middle-aged adults.[10,11]
Average survival for MTC is lower than that for more common thyroid cancers (e.g., 83% 5-year survival for MTC compared with 90% to 94% 5-year survival for papillary and follicular thyroid cancer).[27,28] Survival is correlated with stage at diagnosis, and decreased survival in MTC can be accounted for in part by a high proportion of late-stage diagnosis.[27,28,29]
In addition to early stage at diagnosis, other factors associated with improved survival in MTC include smaller tumor size, younger age at diagnosis, familial versus sporadic form, and diagnosis by biochemical screening (i.e., screening for calcitonin elevation) versus symptoms.[29,30,31,32]
A Surveillance, Epidemiology, and End Results population-based study of 1,252 MTC patients found that survival varied by extent of local disease. For example, the 10-year survival rates ranged from 95.6% for those with disease confined to the thyroid gland to 40% for those with distant metastases.
While the majority of MTC cases are sporadic, approximately 20% to 25% are hereditary because of mutations in the RET proto-oncogene.[33,34,35] Mutations in the RET gene cause MEN2, an autosomal dominant disorder associated with a high lifetime risk of MTC. Multiple endocrine neoplasia type 1 (MEN1) (OMIM) is an autosomal dominant endocrinopathy that is genetically and clinically distinct from MEN2; however, the similar nomenclature for MEN1 and MEN2 may cause confusion. There is no increased risk of thyroid cancer for MEN1. (Refer to the MEN1 section of this summary for more information.)