> Table of Contents > Thyroid Malignant Neoplasia
Thyroid Malignant Neoplasia
James P. Miller, MD
image BASICS
DESCRIPTION
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.
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
image DIAGNOSIS
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
  • Hürthle cell: large eosinophilic cells with granular cytoplasm
  • Medullary: large amounts of amyloid stroma
  • Anaplastic: small cell and giant cell undifferentiated tumors
image TREATMENT
MEDICATION
  • 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
P.1035

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 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
image 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 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.
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%
  • 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.
REFERENCES
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
&NA;
  • 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
&NA;
Multiple Endocrine Neoplasia (MEN) Syndromes
Codes
&NA;
ICD10
C73 Malignant neoplasm of thyroid gland
Clinical Pearls
&NA;
  • 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.