SUN-365 - Very Late Distant Metastasis from Papillary Thyroid Carcinoma Following Prolonged Biochemical Indeterminate Response

Background: Papillary thyroid carcinoma (PTC) is typically associated with excellent long-term outcomes. However, patients with persistent low-level thyroglobulin (Tg) and no identifiable structural disease represent a diagnostic and surveillance challenge. Very late development of distant metastasis in this setting is uncommon and not well characterized.

Clinical

Case: A 67-year-old woman with PTC diagnosed in 2009 underwent total thyroidectomy followed by two radioactive iodine treatments (150 mCi and 200 mCi). Surgical pathology revealed an encapsulated minimally invasive carcinoma with follicular variant papillary features measuring 5.8 × 4.6 cm, with focal capsular and vascular invasion and no extrathyroidal extension. Post-ablation whole-body scan in 2010 was negative, and stimulated Tg in 2014 was negative (0.9 ng/mL). Over the subsequent decade, she demonstrated a prolonged biochemical indeterminate response, with persistently detectable basal Tg ranging from 0.8 to 4.9 ng/mL and intermittently elevated stimulated Tg, peaking at 10.5 ng/mL in 2018. Serial neck ultrasounds with benign lymph node biopsies, CT imaging, and FDG-PET scans failed to identify structural disease. Levels of Tg fluctuated but generally remained low until 2022, when Tg increased to 8.9 ng/mL before spontaneously declining to 6.7 ng/mL with stable imaging. The patient subsequently lost follow-up. She re-presented in 2025 with a marked Tg elevation (326 ng/mL). Multimodal imaging identified a destructive left frontal calvarial lesion. Surgical resection of the lesion with cranioplasty confirmed metastatic well-differentiated thyroid carcinoma consistent with follicular variant PTC. Notably, solitary skull metastasis from differentiated thyroid carcinoma is rare and may delay diagnosis due to its atypical presentation. Given the isolated nature of disease and indolent behavior, multidisciplinary consensus favored close observation.

Conclusion: This case highlights that patients with prolonged biochemical indeterminate response may develop clinically significant distant metastases more than 15 years after initial treatment. Persistent or rising Tg levels, even after extended periods of negative multimodal imaging, should prompt renewed evaluation and reinforce the importance of long-term, risk-adapted surveillance, particularly in patients who fail to achieve an excellent response to therapy.

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