SUN-478 Poorly Differentiated Thyroid Cancer Arising from a Hyperfunctioning Nodule Treated with I-131

Thyroid nodules are a common clinical problem with an incidence of up to 1% in men and 7–15% of cases representing thyroid cancer. Current American Thyroid Association guidelines do not recommend cytologic evaluation of hyperfunctioning nodules as they rarely harbor malignancy. We present a case of a hyperfunctioning nodule which years after ablation was diagnosed as a poorly differentiated thyroid cancer. A 38 year old male had a 4cm thyroid nodule discovered in 1994. Nuclear Medicine (NM) imaging revealed a warm nodule though patient was euthyroid. Biopsy was benign with good sample. Nodule was followed with serial ultrasound (US) and TSH. In 2008 he became hyperthyroid. Scan showed hot nodule and he was given 27.3 mCi I-131 with normalization of the TSH. In 2013 patient again developed hyperthyroidism. NM imaging showed a hot nodule. After 29.5 mCi I-131 he became hypothyroid requiring levothyroxine. Intermittent US showed stability. In early 2019 nodule was 3.7cm, solid and hypoechoic but more heterogeneous. Despite TIRADS recommendation that nodule no longer be followed by US, FNA was performed and revealed Bathesda IV cytology. Gene classification with Thyroseq revealed a TERT mutation. On total thyroidectomy pathology demonstrated a 4.5cm poorly differentiated carcinoma thought to be of follicular origin. Tumor was partially encapsulated with multiple areas of vascular invasion and extensive tumor necrosis. Tumor was present at inked margin but no extrathyroidal extension was noted. There was a <1mm metastasis noted in 1 peri-isthmus lymph node. One month post operatively thyroglobulin was 123.5 ng/mL. I-123 whole body scan demonstrated bilateral uptake in the region of the thyroid suggesting adenopathy; there were similar findings on FDG-PET scan but no adenopathy was identified on US or the CT portion of the PET. Patient was treated with 129mCI of I-131 with focally intense activity in the lower neck on post treatment scan but nothing elsewhere. Follow up lab testing is pending. Though thyroid nodules are a common clinical problem, there are only isolated case reports of hyperfunctioning nodules being later found to have thyroid cancer. One retrospective series of over 6000 patients found a thyroid cancer prevalence of 0.15% in hyperthyroid patients treated with I-131.(i) Poorly differentiated thyroid cancer is thought to occur as a mutation from a differentiated cancer. Here, we present a novel case of the 25 year course of a benign, hyperfunctioning nodule later mutating into an aggressive poorly differentiated cancer. We hypothesize that this nodule mutated late in the course as it was clearly benign on initial biopsy and had a benign course until recent events. This case supports periodic screening of hyperfunctioning nodules after ablation, especially if the nodule does not shrink significantly after I-131. Endnotes (i) Angusti T et al. The Journal of Nuclear Medicine 41(6):1006–1009.