> Table of Contents > Thyroid Malignant Neoplasia
Thyroid Malignant Neoplasia
James P. Miller, MD
image BASICS
Thyroid malignant neoplasia is an autologous growth of thyroid nodules with potential for metastases.
  • Papillary carcinoma
    • Most common variety, 60-70% of thyroid tumors
    • Peak incidence in the 3rd to 4th decades
    • 3 times more common in women
    • May be associated with radiation exposure
    • Tumor contains psammoma bodies, 50%
    • Metastasizes by lymphatic route (30% at time of diagnosis)
    • Multicentric in ≥20%, especially in children
    • Higher risk in patients with Hashimoto thyroiditis
  • Follicular carcinoma
    • 10-20% of thyroid tumors
    • Peak incidence in 5th decade of life
    • Incidence has been decreasing because of the addition of dietary iodine.
    • Metastasizes by the hematogenous route
  • Hürthle cell carcinoma (variant of follicular with poorer prognosis)
    • 2-3% of thyroid malignancies
    • Usually in patients >60 years old
    • No gender difference
    • Radioresistant
    • Composed of distinct large eosinophilic cells with abundant cytoplasmic mitochondria
    • Variant of follicular carcinoma with worse prognosis
  • Medullary thyroid carcinoma (MCT)
    • Arises from parafollicular cells, C cells
    • Multiple endocrine neoplasia (MEN) syndromes (MEN2A, MEN2B, FMTC). Prevalence of MEN2 is 1:30,000.
    • MCT associated with MEN2B occur in childhood, those with MEN2A occur in young adults, and those with FMTC occur at middle age.
    • 3-4% of all thyroid tumors
    • 25-35% are associated with MEN syndromes (2A more common than 2B), which can be familial or sporadic.
    • Calcitonin is a chemical marker.
    • RET proto-oncogene mutation is screened; family members who carry the RET gene should consider early prophylactic thyroidectomy.
  • Anaplastic carcinoma
    • 3% of thyroid tumors
    • Most aggressive form of thyroid neoplasia
    • More common in females
    • Usually in patients >60 years old
  • Other: lymphoma, sarcoma, or metastatic (renal, breast, or lung)
  • System(s) affected: endocrine/metabolic
  • Synonym(s): follicular carcinoma of the thyroid; papillary carcinoma of the thyroid; Hürthle cell carcinoma of the thyroid; anaplastic cell carcinoma of the thyroid
Geriatric Considerations
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.
  • 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
  • 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)
  • 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
  • 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.
Medullary carcinoma: pheochromocytoma, hyperparathyroidism, ganglioneuroma of the GI tract, neuromata of mucosal membranes
  • Neck mass: If fixed to surrounding tissue, this finding suggests advanced disease.
  • Cervical adenopathy
  • Multinodular goiter
  • Thyroid adenoma
  • Thyroglossal duct cyst
  • Thyroiditis
  • Thyroid cyst
  • Ectopic thyroid
  • Dermoid cyst
  • 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
  • Hürthle cell: large eosinophilic cells with granular cytoplasm
  • Medullary: large amounts of amyloid stroma
  • Anaplastic: small cell and giant cell undifferentiated tumors
  • Postoperatively, will require thyroid hormone replacement: Goal is to keep TSH <0.1 mU/L.
  • Levothyroxine (T4, Synthroid) 100 to 200 &mgr;g/day
  • Liothyronine (T3, Cytomel) 50 to 100 &mgr;g/day

  • 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.
  • 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].
  • 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 Hürthle 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
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 131 I 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.
Avoid iodine deficiency.
National Cancer Institute: (301) 496-5583; http://www.cancer.gov
  • Taken together: 5-year survival of thyroid cancer is
  • 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%
  • Hürthle 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. Longterm survivors should have original pathology reexamined.
1. Wells SA Jr, 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.
2. 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.
3. 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.
4. 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
C73 Malignant neoplasm of thyroid gland
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.
  • ˜ 2% 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.