para>Risk of malignancy increases at >60 years old. ‚
Pediatric Considerations
‚
EPIDEMIOLOGY
Incidence
- 12.9/100,000 per year in the United States
- Deaths: 0.5/100,000 per year in the United States
- In 2015, estimated 62,450 new cases and 1,950 deaths from thyroid cancer in the United States
- Predominant age: usually >40 years old
- Predominant sex: female > male (2.6:1) prevalence
- Lifetime risk of developing thyroid cancer is 1.1%
- In 2011, 566,708 patients living with thyroid cancer in the United States
ETIOLOGY AND PATHOPHYSIOLOGY
Unknown ‚
Genetics
- Familial polyposis of the colon, Turcot syndrome, and Gardner syndrome with the APC gene (5q21)
- Medullary: autosomal dominant with MEN syndrome
- BRAF mutation (rare in children)
- RET oncogene (more common in children)
RISK FACTORS
- Family history
- Neck irradiation (6 to 2,000 rads): papillary carcinoma
- Iodine deficiency: follicular carcinoma
- MEN2: medullary carcinoma; autosomal dominant
- Previous history of subtotal thyroidectomy for malignancy: anaplastic carcinoma
- Asian race
- Female gender
GENERAL PREVENTION
- Physical exam in high-risk group
- Calcium infusion or pentagastrin stimulation test screening in high-risk MEN patients
- Screen for RET proto-oncogene in groups at-risk for MCT.
COMMONLY ASSOCIATED CONDITIONS
Medullary carcinoma: pheochromocytoma, hyperparathyroidism, ganglioneuroma of the GI tract, neuromata of mucosal membranes ‚
DIAGNOSIS
HISTORY
- Change in voice (hoarseness)
- Positive family history
- Neck mass
- Dysphagia
- Dyspnea
- Cough
- Difficulty swallowing
PHYSICAL EXAM
- Neck mass: If fixed to surrounding tissue, this finding suggests advanced disease.
- Cervical adenopathy
DIFFERENTIAL DIAGNOSIS
- Multinodular goiter
- Thyroid adenoma
- Thyroglossal duct cyst
- Thyroiditis
- Thyroid cyst
- Ectopic thyroid
- Dermoid cyst
DIAGNOSTIC TESTS & INTERPRETATION
- Medullary carcinoma: calcitonin level (normal <30 pg/mL [300 ng/L]), pentagastrin stimulation test, and RET proto-oncogene
- Thyroglobulin (TG) level: postoperative tumor marker
- DNA content of tumors from biopsy specimen: Diploid content has a better prognosis.
- Thyroid function tests usually normal
- Thyroid scan: 12 " “15% of cold nodules are malignant; rate is higher in patients <40 years of age and those with microcalcifications on US.
- US: Solid mass and microcalcifications are more suspicious of malignancy.
- CT scan and MRI can be useful to evaluate large substernal masses and recurrent soft tissue masses.
- 18F-FDG positron-emission tomographic scan can help if the cytology is inconclusive; helpful with recurrent disease when patient has a negative 131I scan and an elevated TG level
Diagnostic Procedures/Other
- Fine-needle aspiration (FNA)
- Surgical biopsy/excision
- Laryngoscopy if vocal cord paralysis is suspected.
Test Interpretation
- Papillary: psammoma bodies, anaplastic epithelial papillae
- Follicular: anaplastic epithelial cords with follicles
- H ƒ ¼rthle cell: large eosinophilic cells with granular cytoplasm
- Medullary: large amounts of amyloid stroma
- Anaplastic: small cell and giant cell undifferentiated tumors
TREATMENT
MEDICATION
Postoperatively, will require thyroid hormone replacement: Goal is to keep TSH <0.1 mU/L. ‚
- Levothyroxine (T4, Synthroid) 100 to 200 Ž ¼g/day
- Liothyronine (T3, Cytomel) 50 to 100 Ž ¼g/day
GENERAL MEASURES
- Papillary/follicular: 131I thyroid remnant ablation
- Medullary: Vandetanib has been tried in patients with advanced disease (1)[B].
- Anaplastic: Doxorubicin and cisplatin have achieved partial remission in some patients (2)[B].
- Recurrent tumor: Sorafenib has been used in patients with recurrent disease.
ADDITIONAL THERAPIES
- External beam radiation for advanced disease
- 131I is used in high-risk patients with papillary and follicular tumors. The role is to ablate remnant thyroid tissue to improve specificity of future TG assays (3)[C].
SURGERY/OTHER PROCEDURES
- Papillary carcinoma: lobectomy with isthmectomy (if lesion <1 cm) or total thyroidectomy and removal of suspicious lymph nodes. Total thyroidectomy for tumors >1 cm (4)[B]
- Follicular carcinoma and H ƒ ¼rthle cell: total thyroidectomy and removal of suspicious lymph nodes
- Medullary carcinoma: total thyroidectomy with central node dissection; unilateral or bilateral modified radical neck dissection if lateral nodes are histologically positive
- Anaplastic carcinoma: aggressive en bloc thyroidectomy; tracheostomy often required; not responsive to 131I
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- 10 " “30% of initially disease-free patients will develop recurrence and/or metastases. 80% recur in neck and 20% with distant metastases. Lung is most common site of distant metastases.
- Thyroid scan at 6 weeks and administration of 131I for any visible uptake; any evidence of residual thyroid tissue (after total thyroidectomy) or lymph node disease noted on scan is treated with radioactive iodine.
- At 6 months and then yearly, the patient should have a thyroid scan and chest x-ray.
- Papillary and follicular: a TG level should be done yearly. Recombinant human thyroid-stimulating hormone (rhTSH) " “stimulated TG level may be more sensitive.
- Medullary: Calcitonin level should be done yearly with pentagastrin stimulation.
- The thyroid scan and TG level should be done with the patient in the hypothyroid state induced by 6-week withdrawal of levothyroxine or 2- to 3-week withdrawal of liothyronine.
- Decreased incidence of recurrence when TSH is suppressed.
DIET
Avoid iodine deficiency. ‚
PATIENT EDUCATION
National Cancer Institute: (301) 496-5583; http://www.cancer.gov ‚
PROGNOSIS
- Taken together: 5-year survival of thyroid cancer is 97.8%.
- Favorable factors: female, multifocality, regional LN involvement
- Adverse factors: age >45 years, follicular histology, primary tumor >4 cm, extrathyroid extension, distant metastases
- Papillary carcinoma: 10-year overall survival is 93%; 30-year cancer-related death rate of 6%
- Follicular carcinoma: 10-year overall survival is 85%; histologically, microinvasive tumors parallel papillary tumor results, whereas grossly invasive tumors do far worse; 30-year cancer-related death rate of 15%
- H ƒ ¼rthle cell carcinoma: 93% 5-year survival rate and 83% survival rate overall; grossly invasive tumor survival <25%
- Medullary carcinoma: negative nodes, 90% 5-year survival rate and 85% 10-year survival rate; with positive nodes, 65% 5-year survival rate and 40% 10-year survival rate. Prognosis worse for MEN2B compared to MEN2A. Overall 10-year survival is 75%.
- Anaplastic carcinoma: survival unexpected. Long-term survivors should have original pathology reexamined.
COMPLICATIONS
- Recurrence of tumor is 10 " “30%; 80% recur in neck, and 20% recur distally
- Hoarseness from tumor invasion or operative injury to recurrent laryngeal nerve
- Hypoparathyroidism from operative injury to parathyroid glands
REFERENCES
11 Wells ‚ SAJr, Robinson ‚ BG, Gagel ‚ RF, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012;30(2):134 " “141.22 Shimaoka ‚ K, Schoenfeld ‚ DA, DeWys ‚ WD, et al. A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer. 1985;56(9):2155 " “2160.33 Mazzaferri ‚ EL, Jhiang ‚ SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med. 1994;97(5):418 " “428.44 Bilimoria ‚ KY, Bentrem ‚ DJ, Ko ‚ CY, et al. Extent of surgery affects survival for papillary thyroid cancer. Ann Surg. 2007;246(3):375 " “381.
ADDITIONAL READING
- Blamey ‚ S, Barraclough ‚ B, Delbridge ‚ L, et al. Using recombinant human thyroid-stimulating hormone for the diagnosis of recurrent thyroid cancer. ANZ J Surg. 2005;75(1 " “2):10 " “20.
- Burns ‚ WR, Zeiger ‚ MA. Differentiated thyroid cancer. Semin Oncol. 2010;37(6):557 " “566.
- Cox ‚ AE, LeBeau ‚ SO. Diagnosis and treatment of differentiated thyroid carcinoma. Radiol Clin North Am. 2011;49(3):453 " “462, vi.
- Haugen ‚ BR, Pacini ‚ F, Reiners ‚ C, et al. A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer. J Clin Endocrinol Metab. 1999;84(11):3877 " “3885.
- Marsh ‚ DJ, Gimm ‚ O. Multiple endocrine neoplasia: types 1 and 2. Adv Otorhinolaryngol. 2011;70:84 " “90.
- Pitt ‚ SC, Moley ‚ JF. Medullary, anaplastic, and metastatic cancers of the thyroid. Semin Oncol. 2010;37(6):567 " “579.
- Wang ‚ W, Larson ‚ SM, Fazzari ‚ M, et al. Prognostic value of [18F]fluorodeoxyglucose positron emission tomographic scanning in patients with thyroid cancer. J Clin Endocrinol Metab. 2000;85(3):1107 " “1113.
SEE ALSO
Multiple Endocrine Neoplasia (MEN) Syndromes ‚
CODES
ICD10
C73 Malignant neoplasm of thyroid gland ‚
ICD9
193 Malignant neoplasm of thyroid gland ‚
SNOMED
- 94098005 Primary malignant neoplasm of thyroid gland
- 255029007 papillary thyroid carcinoma (disorder)
- 255028004 Follicular thyroid carcinoma
- 255032005 Medullary thyroid carcinoma (disorder)
- 423158009 Hurthle cell carcinoma of thyroid (disorder)
CLINICAL PEARLS
- Standard workup for a patient suspected of having a thyroid cancer is a physical exam, TSH level, neck US, and FNA.
- TG levels can be elevated in several thyroid disorders. Its usefulness comes once the diagnosis of cancer has been made. It serves as a better marker for recurrent disease.
- ¢ ˆ ¼2% of the normal population will have a positive 18F-FDG positron-emission tomographic scan, so it is more useful for postresection follow-up.
- FNA results will be benign, malignant, indeterminate, or nondiagnostic. More helpful in planning initial surgical approach.