Follicular Thyroid Carcinoma

Follicular thyroid carcinoma (FTC) is a well-differentiated thyroid cancer derived from thyroid follicular epithelial cells, accounting for 10-15% of thyroid cancers, with annual incidence of 1-3 per 100,000. FTC predominantly affects women (3:1 ratio) aged 50-60 years (older than papillary). Iodine-deficient regions have higher FTC proportion of thyroid cancers. Pathogenesis involves RAS mutations (40-50%, most common), PAX8/PPARγ rearrangements (30-35%), and PTEN alterations, with progression to poorly differentiated and anaplastic thyroid cancer in subset.

Histopathologic features distinguish FTC from follicular adenoma and papillary thyroid carcinoma. FTC requires demonstration of capsular invasion (penetration through entire fibrous capsule) or vascular invasion (tumor cells in vessels of capsule or beyond) for diagnosis. Variants include minimally invasive FTC (capsular invasion only or limited vascular invasion ≤4 vessels), encapsulated angioinvasive FTC (>4 vessels), and widely invasive FTC (extensive invasion of surrounding thyroid). Hürthle cell carcinoma (oncocytic FTC variant, 3-10% of thyroid cancers) is characterized by oxyphilic cytoplasm, more aggressive behavior, lower iodine avidity, and higher metastatic risk.

Clinical features include painless thyroid nodule (most common), bone pain (skeletal metastases), pulmonary symptoms (lung metastases), neck mass, and rarely paraneoplastic features. Lymph node involvement is uncommon (<5%) compared to PTC. Hematogenous spread predominates with metastases to bones (most common, 30-50% have skeletal metastases at presentation in widely invasive FTC), lungs, brain, liver. Diagnosis includes thyroid ultrasound, fine-needle aspiration cytology (cannot reliably distinguish from follicular adenoma — diagnosis often requires surgical excision), molecular testing for indeterminate FNA (Afirma, ThyroSeq), and staging with neck ultrasound, chest CT, bone scan, and PET-CT for advanced disease. Treatment includes total thyroidectomy for confirmed FTC (lobectomy with completion thyroidectomy if FTC found in lobectomy specimen), prophylactic central neck dissection generally not recommended, lateral neck dissection only for clinically positive nodes, postoperative radioactive iodine ablation for all but smallest minimally invasive FTC, TSH suppression with levothyroxine, and management of metastatic disease with surgery, RAI, external beam radiation, or targeted therapy. Prognosis varies: 10-year survival 75-95% for minimally invasive FTC, 50-75% for widely invasive FTC, lower in advanced or Hürthle cell carcinoma.