Papillary Thyroid Cancer

Background

• Papillary thyroid cancer (PTC) is the most common type of thyroid cancer (reported to account for about 80% of all thyroid cancers).
  • PTC may be sporadic or genetic, and can be subtyped as well differentiated or poorly differentiated, with each subtype encompassing multiple variants (some of which are more aggressive than others).
  • PTC must be differentiated from less common thyroid carcinomas, including:
    • follicular thyroid cancer - also arising from follicular cells and classified as differentiated thyroid cancer
    • Hurthle cell carcinoma - historically classified as a variant of follicular thyroid cancer, but is now recognized as a separate type of differentiated thyroid cancer
    • medullary thyroid cancer - a neuroendocrine tumor arising from parafollicular C cells
    • anaplastic thyroid cancer - the least common and most aggressive thyroid carcinoma, arising de novo or from differentiated thyroid cancer
• Risk factors for PTC include prior exposure to radiation in childhood or adolescence, history of iodine deficiency, excess intake of iodine, and family history of thyroid cancer.
• PTC is usually associated with an excellent prognosis in both adults and children, especially for patients with papillary microcarcinomas (diameter < 1 cm).

Evaluation

• PTC may present as a palpable thyroid nodule noticed by the patient, as a palpable thyroid nodule discovered on a routine physical exam, or as a nonpalpable nodule detected incidentally on imaging.
• Characteristics suggesting malignancy include:
  • thyroid nodules that are firm, fixed, growing, or associated with cervical adenopathy
  • presence of dysphonia
  • suspicious ultrasound findings, such as hypoechogenicity, microcalcification, irregular margins, increased vascularity, being solid, and evidence of pathologic adenopathy
• Fine needle aspiration biopsy and cytology are the preferred methods of diagnosing papillary thyroid cancer.
  • Thyroid biopsy specimens are diagnosed as PTC based on typical nuclear characteristics that appear on a biopsy smear.
  • Typical nuclear characteristics of PTC include:
    • nuclear pseudoinclusions (due to cytoplasmic invaginations)
    • nuclear grooves (folds in the nuclear membrane)
    • psammoma bodies (calcium salt deposits)
    • papillary structure
• Postoperative histological evaluation of a surgical specimen can help distinguish characteristics of aggressive variants of papillary thyroid cancer.
  • This more specific diagnosis, along with postoperative staging, can help guide risk stratification and further management.
  • Aggressive variants may warrant changes to the management plan as they are associated with worse prognosis than nonaggressive variants.

Management

• Surgery for primary tumor resection is the first-line treatment for most patients with papillary thyroid cancer.
  • For follicular cell-derived malignancies, the extent of surgery depends on size of cancer, degree of extrathyroidal extension, and presence of nodal metastases (Strong recommendation).
  • Most cases of differentiated thyroid cancer are treated with a total or near-total thyroidectomy.
    • A thyroidectomy eliminates the need for additional surgery to remove the contralateral lobe should recurrence happen.
    • Experienced thyroid surgeons can safely perform a thyroidectomy with minimal complications.
    • Total removal of the thyroid facilitates postoperative procedures, including:
      • radioactive iodine (RAI) therapy for ablating microscopic disease remnants
      • thyroglobulin measurement and RAI whole body scans to detect recurrence or metastases
  • For malignancies treated with a near-total or total thyroidectomy, central or lateral neck dissection may be indicated.
    • Include a central compartment neck dissection if there are any clinically involved central lymph nodes (Strong recommendation).
    • Include a lateral compartment neck dissection if there are biopsy-proven lateral lymph node metastases (Strong recommendation).
  • Treat follicular cell-derived malignancies with a lobectomy if any of the following (Strong recommendation):
    • thyroid cancer < 1 cm with no extrathyroidal extension or evidence of lymph node metastases
    • small, unifocal, intrathyroidal carcinomas in absence of familial thyroid carcinoma, prior head or neck radiation therapy, or detected cervical nodal metastases
  • Perform a postoperative evaluation that includes measurement of serum thyroglobulin to confirm disease status and conduct postoperative staging to provide information for risk stratification and postoperative patient management (Strong recommendation).
• Active surveillance (patient observation with serial cervical ultrasound examinations typically performed every 6-12 months) can be used as an alternative to surgery in patients with papillary thyroid carcinoma and any of the following:
  • very low risk tumors, such as those with papillary microcarcinomas without clinically evident metastases or local invasion and no cytologic evidence of aggressive disease
  • high surgical risk due to comorbidities
  • a relatively limited remaining life span (for example, due to serious cardiopulmonary disease, other malignancies, or very advanced age)
  • medical or surgical issues that need to be addressed before thyroid surgery
• Use thyroid-stimulating hormone (TSH) suppression therapy to reduce recurrence risk following thyroid surgery and RAI remnant ablation (Strong recommendation).
  • Suppress TSH to < 0.1 milliunits/L initially in patients with high-risk thyroid cancer (Strong recommendation).
  • Consider maintaining TSH at lower end of reference range (0.5-2 milliunits/L) in patients with low-risk thyroid cancer who received lobectomy or who received remnant ablation and have undetectable serum thyroglobulin (Tg) levels (Weak recommendation).
  • Consider maintaining TSH slightly below lower end of reference range (0.1-0.5 milliunits/L) in patients with low-risk thyroid cancer who received remnant ablation and have low serum Tg levels (Weak recommendation).
• Consider RAI therapy for postoperative remnant ablation to destroy residual thyroid tissue, and to eliminate persistent disease and suspected micrometastases in most patients with stage II-IV disease, and in some patients with stage I disease.
  • Either recombinant human TSH (rhTSH) or thyroid hormone withdrawal may be considered in preparation for RAI therapy (depending on the patient), although rhTSH stimulation should be considered as alternative to thyroid hormone withdrawal in patients at any American Thyroid Association (ATA) risk category with significant comorbidity that might preclude thyroid hormone withdrawal (Strong recommendation).
  • RAI dosing:
    • RAI dose of 30 millicuries (mCi) generally favored over higher dose for remnant ablation in patients in low-risk category or in intermediate-risk ATA category with lower risk features, such as low volume central neck nodal metastases with no other known gross residual disease or other adverse features (Strong recommendation)
    • Higher RAI doses (> 30 mCi) may be needed for some patients.
  • Use RAI to treat pulmonary micrometastases (Strong recommendation), and consider RAI to treat other metastases that concentrate radioiodine (Weak recommendation).
• Provide follow-up.
  • Periodically perform (for example, every 6-12 months) serum TSH, thyroglobulin, and thyroglobulin antibody measurements, neck ultrasounds, and clinical exams.
  • Perform posttreatment whole body scan in patients who have had RAI remnant ablation (Strong recommendation).
• Consider kinase inhibitors for patients with RAI-refractory, metastatic, symptomatic, rapidly progressive, and/or imminently threatening differentiated thyroid cancer (DTC) that is not amenable to other therapies (Weak recommendation).
• Consider cytotoxic chemotherapy for patients with RAI-refractory, metastatic, symptomatic, rapidly progressive, and/or imminently threatening DTC that is not amenable to other therapies, including kinase inhibitors (Weak recommendation).