Follicular Thyroid Carcinoma

Follicular thyroid carcinoma is a differentiated malignancy of follicular cells that shows capsular or vascular invasion, with no nuclear features of papillary carcinoma. It makes up 10 to 15% of thyroid cancers, with a higher share in iodine-deficient regions. Mean age is 50 years, and women are affected about three times as often as men.

Molecular drivers are RAS mutations and the PAX8-PPARG rearrangement, with TERT promoter mutations marking poor outcome.

Subtypes by invasion

• Minimally invasive (capsular invasion only) with an excellent outlook
• Encapsulated angioinvasive: invasion of vessels in or beyond the capsule, with a risk that rises with the number of invaded vessels (4 or more is high)
• Widely invasive: infiltrates thyroid tissue and vessels

Oncocytic (Hurthle cell) carcinoma is a variant with a more frequent chance of being radioiodine-resistant.

Spread is hematogenous, to lung, bone and brain, and lymph node metastasis is uncommon (about 5%). Ten-year survival is 85 to 95% overall, falling to about 50% in widely invasive disease and with distant metastases. Poor prognostic factors are age over 45, size over 4 cm, widely invasive histology, distant disease and oncocytic type. Complications: bone metastases with fracture and cord compression, and recurrence.

• A solitary thyroid nodule, euthyroid in most
• Rapid growth, hoarseness or dysphagia in advanced tumors
• Bone pain, pathologic fracture or neurological signs from metastases
• Red flags: a large fixed nodule, bone pain and a raised thyroglobulin

1. TSH and neck ultrasound (a solid, often isoechoic or hyperechoic nodule with a halo).
2. Fine-needle aspiration: a follicular neoplasm or suspicious category, which cannot distinguish adenoma from carcinoma because the diagnosis needs histologic proof of invasion.
3. Molecular testing of indeterminate cytology can help estimate the risk.
4. Diagnostic lobectomy with full capsule sampling for histology, reporting the number of vessels invaded and the extent of capsular invasion.
5. Staging for invasive disease: CT chest, bone imaging (MRI, bone scan or fluorodeoxyglucose PET-CT), and whole-body radioiodine scan after thyroidectomy.
6. Serum thyroglobulin (a tumor marker after total thyroidectomy).

Differentials: follicular adenoma, follicular variant of papillary carcinoma, medullary carcinoma, hyperfunctioning nodule, thyroid metastasis.

1. Diagnostic lobectomy for a follicular neoplasm. If histology shows minimally invasive carcinoma without vascular invasion and the tumor is small, lobectomy may suffice.
2. Completion or total thyroidectomy for vascular invasion, widely invasive carcinoma, tumors over 4 cm, or distant disease. Cefazolin 2 g IV before incision (3 g if over 120 kg). Postoperative calcium monitoring and calcium carbonate 1 to 2 g elemental calcium daily with calcitriol 0.25 to 1 microgram daily when needed.
3. Levothyroxine 1.6 micrograms/kg orally once daily, with TSH goal by risk (0.1 to 0.5 mIU/L intermediate, under 0.1 mIU/L high risk).
4. Radioiodine for angioinvasive, widely invasive and metastatic disease: 100 to 150 millicuries (3.7 to 5.5 GBq) for ablation, and 150 to 200 millicuries (5.5 to 7.4 GBq) every 6 to 12 months for metastases while iodine-avid. Prepare with recombinant TSH 0.9 mg IM on two consecutive days or levothyroxine withdrawal, and a low-iodine diet for 1 to 2 weeks.
5. Bone metastases: surgical resection or stabilization for solitary lesions and impending fracture, external radiotherapy 8 Gy in 1 fraction or 20 Gy in 5 fractions, zoledronic acid 4 mg IV every 4 weeks, or denosumab 120 mg SC every 4 weeks with calcium and vitamin D (cholecalciferol 800 to 1000 IU daily).
6. Radioiodine-refractory progressive disease: lenvatinib 24 mg orally once daily, sorafenib 400 mg orally twice daily, or cabozantinib 60 mg orally once daily. Monitor blood pressure, proteinuria, liver tests and wound healing.
7. Oncocytic carcinoma: surgery with thyroid hormone suppression, since radioiodine rarely works, and systemic therapy.

Follow-up: thyroglobulin with anti-thyroglobulin antibodies and neck ultrasound at 6 to 12 months and yearly, with whole-body imaging for a rising marker. Counsel on lifelong levothyroxine and on bone symptoms.