Thyroid cancer represents approximately 1% of malignancies occurring in the United States, accounting for an estimated 23,600 cancer diagnoses and 1,460 [1] cancer deaths per year. Of these cancers, 3% to 4% are medullary thyroid cancer (MTC).[2] 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.[2,3] 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 diagnoses.[2-4] A Surveillance, Epidemiology, and End Results (SEER) population-based study of papillary, follicular, and medullary thyroid cancers found that survival varied by extent of local disease. For example, among men, 5-year survival rates ranged from 84% for disease confined to the thyroid gland to 35% for extensive, locally advanced disease.[3]

MTC arises from the parafollicular calcitonin-secreting cells of the thyroid gland. MTC occurs in sporadic and familial forms, and may be preceded by C-cell hyperplasia (CCH), although CCH is a relatively common abnormality in middle-aged adults. In a population-based study in Sweden, 26% of patients with MTC were familial.[5] A French national registry and a US clinical series both reported a higher proportion of familial cases (43% and 44%, respectively).[4,6] Familial cases often indicate the presence of multiple endocrine neoplasia type 2 (MEN 2), a group of autosomal dominant genetic disorders caused by inherited mutations in the RET oncogene.

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, and diagnosis by biochemical screening (that is, screening for calcitonin elevation) versus symptoms.[4-6]

References

1. American Cancer Society.: Cancer Facts and Figures 2004. Atlanta, Ga: American Cancer Society, 2004. Also available online. ¹ Last accessed September 27, 2004. 
   
   
2. Hundahl SA, Fleming ID, Fremgen AM, et al.: A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995 [see comments] Cancer 83 (12): 2638-48, 1998.  [PUBMED Abstract]
   
   
3. Bhattacharyya N: A population-based analysis of survival factors in differentiated and medullary thyroid carcinoma. Otolaryngol Head Neck Surg 128 (1): 115-23, 2003.  [PUBMED Abstract]
   
   
4. Modigliani E, Vasen HM, Raue K, et al.: Pheochromocytoma in multiple endocrine neoplasia type 2: European study. The Euromen Study Group. J Intern Med 238 (4): 363-7, 1995.  [PUBMED Abstract]
   
   
5. Bergholm U, Bergström R, Ekbom A: Long-term follow-up of patients with medullary carcinoma of the thyroid. Cancer 79 (1): 132-8, 1997.  [PUBMED Abstract]
   
   
6. Kebebew E, Ituarte PH, Siperstein AE, et al.: Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems. Cancer 88 (5): 1139-48, 2000.  [PUBMED Abstract]
   
   

Glossary Terms

Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).

A change in the usual DNA sequence at a particular gene locus. Mutations (including polymorphisms) can be harmful, beneficial, or neutral.

This term has two meanings. It is sometimes used to differentiate cancers occurring in people who do not have a germline mutation that confers increased susceptibility to cancer from cancers occurring in people who are known to carry a mutation. Cancer developing in people who do not carry a high-risk mutation is referred to as sporadic cancer. The distinction is not absolute, because genetic background may influence the likelihood of cancer even in the absence of a specific predisposing mutation. Alternatively, sporadic is also sometimes used to describe cancer occurring in individuals without a family history of cancer.