General Medical Information

Thyroid Cancer

Carcinoma of the thyroid gland is an uncommon cancer but, nonetheless, is the most common malignancy of the endocrine system.[1] Differentiated tumors (papillary or follicular) are highly treatable and usually curable. Poorly differentiated cancers (medullary or anaplastic) are much less common, are aggressive, metastasize early, and have a much poorer prognosis. Thyroid cancer affects women more commonly than men, and the majority of cases occur in patients between the ages of 25 and 65. The incidence of this malignancy has been increasing over the last decade. The prognosis for differentiated carcinoma is better for patients younger than 40 years of age without extracapsular extension or vascular invasion.[2-6] Age appears to be the single most important prognostic factor.[4] Thyroid cancer commonly presents as a cold nodule. The overall incidence of cancer in a cold nodule is 12% to 15%, but it is higher in patients under 40 years of age.[7]

The prognostic significance of lymph node status is controversial. One retrospective surgical series of 931 previously untreated patients with differentiated thyroid cancer found that female gender, multifocality, and regional node involvement are favorable prognostic factors.[8] Adverse factors included age over 45 years, follicular histology, primary greater than 4 centimeters (T2-3), extrathyroid extension (T4), and distant metastases.[8,9] Other studies, however, have shown that regional lymph node involvement had no effect [10,11] or even an adverse effect on survival.[5,6,12] Diffuse, intense immunostaining for vascular endothelial growth factor in patients with papillary cancer has been associated with a high rate of local recurrence and distant metastases.[13] An elevated serum thyroglobulin level correlates strongly with recurrent tumor when found in patients with differentiated thyroid cancer during postoperative evaluations.[14,15] Serum thyroglobulin levels are most sensitive when patients are hypothyroid and have elevated serum thyroid-stimulating hormone levels.[16] Expression of the tumor suppressor gene p53 has also been associated with an adverse prognosis for patients with thyroid cancer.[17]

Patients considered to be low-risk by the age, metastases, extent, and size (AMES) risk criteria include women younger than 50 years of age and men younger than 40 years of age without evidence of distant metastases. Also included in the low-risk group are older patients with primary tumors less than 5 centimeters and papillary cancer without evidence of gross extrathyroid invasion or follicular cancer without either major capsular invasion or blood vessel invasion.[3] Using these criteria, a retrospective study of 1019 patients showed that the 20-year survival rate is 98% for low-risk patients and 50% for high-risk patients.[3]

Patients with a history of radiation administered in infancy and childhood for benign conditions of the head and neck, such as enlarged thymus, acne, or tonsillar or adenoidal enlargement have an increased risk of cancer as well as other abnormalities of the thyroid gland. In this group of patients, malignancies of the thyroid gland first appear beginning as early as 5 years following radiation and may appear 20 or more years later.[18] Radiation exposure as a consequence of nuclear fall-out has also been associated with a high risk of thyroid cancer, especially in children.[19] Other risk factors for the development of thyroid cancer include a history of goiter, family history of thyroid disease, female gender, and Asian race.[20] The thyroid gland may occasionally be the site of other primary tumors, including sarcomas, lymphomas, epidermoid carcinomas, and teratoma, and may be the site of metastasis from other cancers, particularly of the lung, breast, and kidney.

References

1. 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.

2. Grant CS, Hay ID, Gough IR, et al.: Local recurrence in papillary thyroid carcinoma: is extent of surgical resection important? Surgery 104 (6): 954-62, 1988.

3. Sanders LE, Cady B: Differentiated thyroid cancer: reexamination of risk groups and outcome of treatment. Arch Surg 133 (4): 419-25, 1998.

4. Mazzaferri EL: Treating differentiated thyroid carcinoma: where do we draw the line?. Mayo Clin Proc 66(1): 105-111, 1991.

5. Staunton MD: Thyroid cancer: a multivariate analysis on influence of treatment on long-term survival. Eur J Surg Oncol 20 (6): 613-21, 1994.

6. Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 97 (5): 418-28, 1994.

7. Tennvall J, Biörklund A, Möller T, et al.: Is the EORTC prognostic index of thyroid cancer valid in differentiated thyroid carcinoma? Retrospective multivariate analysis of differentiated thyroid carcinoma with long follow-up. Cancer 57 (7): 1405-14, 1986.

8. Shah JP, Loree TR, Dharker D, et al.: Prognostic factors in differentiated carcinoma of the thyroid gland. Am J Surg 164 (6): 658-61, 1992.

9. Andersen PE, Kinsella J, Loree TR, et al.: Differentiated carcinoma of the thyroid with extrathyroidal extension. Am J Surg 170 (5): 467-70, 1995.

10. Coburn MC, Wanebo HJ: Prognostic factors and management considerations in patients with cervical metastases of thyroid cancer. Am J Surg 164 (6): 671-6, 1992.

11. Voutilainen PE, Multanen MM, Leppäniemi AK, et al.: Prognosis after lymph node recurrence in papillary thyroid carcinoma depends on age. Thyroid 11 (10): 953-7, 2001.

12. Sellers M, Beenken S, Blankenship A, et al.: Prognostic significance of cervical lymph node metastases in differentiated thyroid cancer. Am J Surg 164 (6): 578-81, 1992.

13. Lennard CM, Patel A, Wilson J, et al.: Intensity of vascular endothelial growth factor expression is associated with increased risk of recurrence and decreased disease-free survival in papillary thyroid cancer. Surgery 129 (5): 552-8, 2001.

14. van Herle AJ, van Herle KA: Thyroglobulin in benign and malignant thyroid disease. In: Falk SA: Thyroid disease: endocrinology, surgery, nuclear medicine, and radiotherapy. Philadelphia: Lippincott-Raven, 1997, pp 601-618.

15. Ruiz-Garcia J, Ruiz de Almodóvar JM, Olea N, et al.: Thyroglobulin level as a predictive factor of tumoral recurrence in differentiated thyroid cancer. J Nucl Med 32 (3): 395-8, 1991.

16. Duren M, Siperstein AE, Shen W, et al.: Value of stimulated serum thyroglobulin levels for detecting persistent or recurrent differentiated thyroid cancer in high- and low-risk patients. Surgery 126 (1): 13-9, 1999.

17. Godballe C, Asschenfeldt P, Jørgensen KE, et al.: Prognostic factors in papillary and follicular thyroid carcinomas: p53 expression is a significant indicator of prognosis. Laryngoscope 108 (2): 243-9, 1998.

18. Fraker DL, Skarulis M, Livolsi V: Thyroid tumors. In: DeVita VT, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2001, pp 1740-1762.

19. Pacini F, Vorontsova T, Molinaro E, et al.: Prevalence of thyroid autoantibodies in children and adolescents from Belarus exposed to the Chernobyl radioactive fallout. Lancet 352 (9130): 763-6, 1998.

20. Iribarren C, Haselkorn T, Tekawa IS, et al.: Cohort study of thyroid cancer in a San Francisco Bay area population. Int J Cancer 93 (5): 745-50, 2001.