[Note: Many of the medical and scientific terms used in this summary are found in the NCI Dictionary of Genetics Terms ¹. When a linked term is clicked, the definition will appear in a separate window.]

Thyroid cancer represents approximately 1% of malignancies occurring in the United States, accounting for an estimated 37,340 cancer diagnoses and 1,590 cancer deaths per year.[1] Of these cancers, 2% to 3% are medullary thyroid cancer (MTC).[2,3] Average survival for MTC is lower than that for more common thyroid cancers, e.g., 83% 5-year survival for MTC compared to 90% to 94% 5-year survival for papillary and follicular thyroid cancer.[3,4] 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.[3-5] A Surveillance, Epidemiology, and End Results (SEER) population-based study of 1,252 medullary thyroid cancer patients found that survival varied by extent of local disease. For example, the 10-year survival rates ranged from 95.6% for disease confined to the thyroid gland to 40% for those with distant metastases.[6]

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), though CCH is a relatively common abnormality in middle-aged adults. In a population-based study in Sweden, 26% of patients with MTC had the familial form.[7] A French national registry and a U.S. clinical series both reported a higher proportion of familial cases (43% and 44%, respectively).[5,8] Familial cases often indicate the presence of multiple endocrine neoplasia type 2, a group of autosomal dominant genetic disorders caused by inherited mutations in the RET proto-oncogene (OMIM) ².

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.[5-8]

References

1. American Cancer Society.: Cancer Facts and Figures 2008. Atlanta, Ga: American Cancer Society, 2008. Also available online. ³ Last accessed October 1, 2008. 
   
   
2. Incidence: Thyroid Cancer. Bethesda, Md: National Cancer Institute, SEER, 2004. Available online ⁴. Last accessed March 7, 2007. 
   
   
3. 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]
   
   
4. 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]
   
   
5. 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]
   
   
6. Roman S, Lin R, Sosa JA: Prognosis of medullary thyroid carcinoma: demographic, clinical, and pathologic predictors of survival in 1252 cases. Cancer 107 (9): 2134-42, 2006.  [PUBMED Abstract]
   
   
7. 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]
   
   
8. 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 phenotype or trait that occurs with greater frequency in a given family than in the general population; familial traits may have a genetic and/or nongenetic etiology.

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

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.