MON-412 - Hidden Malignancy: Metastatic Follicular Thyroid Cancer Presenting with Initial False-Negative Biopsy

Follicular thyroid carcinoma (FTC) accounts for 10–15% of thyroid cancers and spreads in 20% of cases. Diagnosis is challenging as malignancy may be missed on fine-needle aspiration (FNA) or thyroidectomy. We present a case of a 50-year-old woman who developed metastatic disease years after a benign thyroidectomy.

A 50-year-old woman with history of subclinical hyperthyroidism and thalassemia trait, was found to have bilateral thyroid nodules on ultrasound. FNA showed a Bethesda IV 7-mm microfollicular lesion, prompting a total thyroidectomy in 2019. Pathology revealed follicular adenomas, adenomatous nodules, and lymphocytic thyroiditis without malignancy. She was started on levothyroxine.

Three years after initial thyroidectomy, she presented with acute chest, neck, back pain, and progressive exertional dyspnea. Chest CT angiography revealed bilateral pulmonary nodules up to 7 mm. Wedge resection of the left lower lobe and biopsy showed thyroid tissue suspicious for metastatic carcinoma. External review of the original thyroidectomy slides again showed no malignancy. Bronchoalveolar lavage was negative. Thyroid US showed no residual tissue and an enlarged right level 2A lymph node, with FNA negative for malignancy.

Whole-body iodine scintigraphy revealed iodine-avid lesions in the lungs, head, and abdomen consistent with metastatic spread. After Thyrogen stimulation, she received 195 mCi of Radioactive Iodine (RAI). Labs showed TSH 66.86 µIU/L (0.39-4.08 µIU/L) and thyroglobulin (Tg) of 73.9ng/mL (1.60-59.90 ng/mL) with undetectable Tg antibodies. Post-therapy uptake scan demonstrated uptake in the neck, lungs and abdomen without new lesions. Six months later, repeat whole-body scan showed persistent prior iodine-avid areas with otherwise physiological uptake. She was followed with serial tg measurements and cross-sectional imaging, showing progressive resolution of the pulmonary metastases and no metastatic foci on CT neck/chest/abdomen/pelvis, brain MRI, or thyroid US. Patient remains asymptomatic without recurrence 2.5 years post-RAI.

This case highlights the diagnostic challenges of FTC, which can spread despite reassuring cytology and negative histology. FTC is more prone than papillary thyroid carcinoma to hematogenous dissemination, potentially leading to delayed recognition. It underscores the importance of long-term surveillance in patients with indeterminate nodules or risk features.

Patient’s progression reinforces the key role of RAI as first-line therapy in iodine-avid disease. She showed excellent biochemical and radiologic response, achieving durable remission over two years, demonstrating RAI’s therapeutic potential in metastatic FTC with preserved iodine uptake. Clinicians should monitor delayed systemic involvement in FTC and utilize RAI judiciously, as it can achieve durable remission even in late-presenting disease.

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