follicular thyroid carcinoma

Follicular thyroid carcinoma accounts for ~10-15% of thyroid cancers and is more common in iodine-deficient regions. It typically presents as a solitary, painless thyroid nodule, often in middle-aged women. Unlike papillary carcinoma, FTC cannot be diagnosed by FNA cytology alone because the key diagnostic feature—capsular and/or vascular invasion—requires evaluation of the tumor's architectural relationship with surrounding tissue, only assessable on histologic examination of the entire excised specimen (i.e., after lobectomy or thyroidectomy). FNA typically shows a 'follicular neoplasm,' which is indeterminate and cannot distinguish benign follicular adenoma from malignant follicular carcinoma.

Pathophysiology: FTC arises from follicular cells and is associated with RAS mutations and PAX8-PPARG rearrangements, in contrast to papillary carcinoma's association with RET/PTC rearrangements and BRAF mutations. Grossly, follicular carcinomas often appear as encapsulated, well-differentiated lesions grossly resembling adenomas, but microscopically show invasion through the capsule or into blood vessels—hence the need for full histologic assessment rather than cytology.

Metastatic spread is hematogenous rather than lymphatic, commonly to bone and lung, which can sometimes be the presenting sign (e.g., pathologic fracture). This is a key board-relevant distinguishing feature from papillary thyroid carcinoma, which spreads primarily via lymphatics to cervical lymph nodes.

Progostically, FTC generally has a good prognosis if treated appropriately (surgery ± radioactive iodine ablation), though it's more aggressive than papillary carcinoma when there is extensive vascular invasion or distant metastasis. Hurthle cell (oncocytic) variant is a subtype with oxyphilic cells packed with mitochondria, which behaves more aggressively and is less iodine-avid, making radioactive iodine therapy less effective.

Treatment: total or near-total thyroidectomy followed by radioactive iodine ablation for high-risk cases, and levothyroxine for TSH suppression thereafter. Serum thyroglobulin serves as a tumor marker to monitor for recurrence.