Follicular Thyroid Cancer

Background

• Follicular thyroid cancer (FTC) is a carcinoma that arises from thyroid follicular cells, is classified as a differentiated thyroid cancer, and accounts for about 10%-20% of all thyroid cancers.
  • FTC may be sporadic or genetic, and can be subtyped as invasive or minimally invasive.
  • FTC must be differentiated from other thyroid carcinomas, including:
    • papillary thyroid cancer, which also arises from follicular cells and is classified as 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
    • Hürthle cell carcinoma, which was historically classified as a variant of follicular thyroid cancer, but is now recognized as a separate type of differentiated thyroid cancer
• Risk factors for malignancy in patients with thyroid nodules include age < 14 years or > 70 years, a history of head or neck radiation therapy, or a family history of thyroid cancer.
• FTC is often asymptomatic and presents as a thyroid nodule palpated on a physical exam or as an incidental finding on imaging.

Evaluation

• Suspect malignancy in patients with thyroid nodules that are firm, fixed, growing, or associated with cervical adenopathy, dysphonia, dysphagia, or dyspnea.
• Perform a thyroid ultrasound in patients with known or suspected thyroid nodules (Strong recommendation).
• Measure serum thyroid-stimulating hormone (TSH) in all patients with thyroid nodules (Strong recommendation).
• Perform scintigraphy (radionuclide scanning) if TSH is low (Strong recommendation). Pregnant women should avoid the use of radioactive agents for diagnostic purposes (Strong recommendation).
• Perform an FNA biopsy of nodules seen on ultrasound if the nodule is ≥ 1 cm in diameter and has ultrasound features suspicious for malignancy (Strong recommendation). Recommendations vary regarding use of FNA biopsy in other circumstances.
• An FNA biopsy is insufficient for the definitive diagnosis of follicular thyroid cancer, and lesions with follicular cytology on an FNA biopsy need further evaluation to confirm a diagnosis.
  • FNA cannot distinguish between follicular adenoma and carcinoma.
  • Surgical excision with diagnostic histopathology is the gold standard for definitive diagnosis of follicular thyroid cancer. However, for FNA cytology results showing follicular neoplasms and follicular lesions of undetermined significance (FLUS), further evaluation with molecular testing of FNA aspirates may be used in combination with clinical and ultrasound features to help determine likelihood of malignancy instead of proceeding directly to surgical excision (Weak recommendation).
  • If molecular testing is not performed or is inconclusive, surgical excision with diagnostic histopathology is recommended for definitive diagnosis of follicular thyroid cancer (Strong recommendation).
• An FNA biopsy is generally not recommended for nodules classified as hyperfunctioning ("hot") on scintigraphy (Weak recommendation). Patients with hyperfunctioning nodules have a low risk for malignancy and should be evaluated for hyperthyroidism.
• Perform a neck ultrasound of the contralateral thyroid lobe and cervical lymph nodes for preoperative staging in any patient having a thyroidectomy for malignant cytologic findings on biopsy (Strong recommendation).

Management

• Surgery is recommended for diagnostic confirmation and primary tumor resection.
  • 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 (including follicular 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 indeterminate nodules, the extent of surgery depends on risk factors for malignancy and patient preference (a total or near-total thyroidectomy is recommended if the nodule is high-risk, a lobectomy if it is lower risk) (Strong recommendation).
  • 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 or lateral lymph nodes (Strong recommendation).
    • Include a lateral compartment neck dissection if there are biopsy-proven lateral lymph node metastases (Strong recommendation).
  • Completion thyroidectomy is suggested in patients for whom a total or near-total thyroidectomy would have been recommended if the diagnosis had been available before surgery (Strong recommendation).
• Thyroid-stimulating hormone (TSH) suppression therapy
  • Use TSH suppression therapy to reduce recurrence risk following thyroid surgery and radioactive iodine remnant ablation (Strong recommendation).
  • Consider TSH suppression therapy to treat slowly progressive pulmonary metastatic disease (Weak recommendation).
• Radioactive iodine (RAI) therapy
  • Consider RAI 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.
  • Perform a posttreatment whole body scan in patients who have had RAI remnant ablation (Strong recommendation).
  • Use RAI to treat pulmonary micrometastases (Strong recommendation), and consider RAI to treat other metastases that concentrate radioiodine (Weak recommendation).
• Provide follow-up with periodic blood tests (including thyroid-stimulating hormone, stimulated serum thyroglobulin, and thyroglobulin antibody measurements), as well as cervical ultrasound and other possible imaging.
• 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).