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Thyroid Malignant Neoplasia

para>Risk of malignancy increases at >60 years old. ‚  
Pediatric Considerations

  • >60% of thyroid nodules are malignant.

  • <2% of thyroid malignancies occur in children and adolescents.

‚  

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.
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