A Subtype of Papillary Thyroid Carcinoma Bone Metastasis With Excellent Response to RAI-Therapy

Introduction: Bone metastases from differentiated thyroid cancer are generally resistant to radioactive iodine (RAI) therapy and are associated with poor prognosis, except for RAI-avid bone metastases with no structural correlate on imaging studies. Case: A 59 y/o woman presented for the evaluation of non-toxic multinodular goiter. Thyroid US showed a 2.7 cm nodule meeting FNAB criteria and no suspicious cervical lymph nodes. Cytology reported a Bethesda IV category with ThyroSeq V3 positive for chromosomal copy number alterations and a high Na+/I− symporter (NIS) expression (27%) with an ~ 60% probability of cancer. The patient underwent left lobectomy with isthmusectomy without neck dissection. Surgical pathology showed a 3.5 cm papillary thyroid carcinoma with extensive angioinvasion (≥4 vessels), negative margins, no ETE, and did not contain a BRAF V600E mutation. Completion thyroidectomy, in anticipation of RAI treatment, showed no additional tumor. Post-operative Tg after 6 weeks was unexpectedly high at 69 ng/mL (negative Tg Ab, TSH 5.7 uIU/ml) which prompted a rhTSH I-123 RAI WBS with SPECT/ CT and a diagnostic chest CT to uncover possible distant metastases. There was RAI uptake in the thyroid bed and right anterolateral 9(th)rib without a CT correlate (no osteolytic lesion) but with a signal abnormality on MRI. She was categorized as T2NxM1, 8(th) Edition AJCC Stage IVB, and ATA high risk. She was treated with 148.3 mCi I-131. Unfortunately, 6 months later the Tg was elevated and rising (Tg 38.4 ng/mL, negative Tg Ab, TSH 0.05 uIU/ml). A second diagnostic I-123 WBS with SPECT/ CT showed a new recurrence in the neck but no uptake in the rib lesion on planar images or other distant sites. Because of the unusually high Tg without any RAI-avid metastatic disease, an 18-FDG PET/CT was ordered to search for non-RAI avid disease. This showed disease confined to the neck and increased sclerosis of the rib lesion without increased FDG-uptake consistent with treated disease status post-RAI. There were no other distant hypermetabolic lesions. The left thyroid bed lesion was biopsied and consistent with Bethesda VI cytology and she will soon undergo left central neck dissection with tumor resection. Discussion: RAI-avid bone metastases without structural correlate on high-resolution imaging are a subtype of bone metastases located in the marrow. They do not present as the typical lytic lesions from cortical destruction. They often resolve following RAI treatment, do not cause skeletal-related complications, and do not significantly affect prognosis. The combination of high NIS expression and increased vascularity in the bone marrow (as opposed to the protected microenvironment in the bone cortex) makes them vulnerable to RAI treatment. Recognition of this subset of bone lesions may prevent overtreatment with high doses of RAI treatment and avoid the use of bisphosphonates or external beam radiation.