SAT-360 - RET Fusion-Positive Poorly Differentiated Thyroid Cancer in A 92-Year-Old Patient Treated with Targeted Therapy using Selpercatinib: A Case Report.

Background: 
Poorly differentiated thyroid carcinoma (PDTC) is a rare, aggressive follicular cell–derived malignancy accounting for approximately 1.8% of thyroid cancers in the United States. It demonstrates high metastatic potential and frequent resistance to radioactive iodine (RAI). As an oncogenic driver, RET fusion activates constitutive RET kinase signaling and promotes tumor growth. Selpercatinib is a selective RET inhibitor that blocks aberrant RET signaling and is FDA-approved for RET fusion–positive thyroid cancers. However, data in PDTC for elderly patients remain limited.

Case Presentation: 
A 92-year-old woman with long-standing metastatic papillary thyroid carcinoma (PTC) presented with progressive cough and dyspnea. Chest CT revealed bilateral pleural effusions. Her history included left thyroid lobectomy for a reportedly benign lesion complicated by permanent left recurrent laryngeal nerve paralysis in the 1960s. In 2010, she underwent complete thyroidectomy with left neck dissection and RAI for metastatic PTC. Over the next decade, she experienced multiple regional and distant recurrences managed with repeat neck dissections, radiotherapy, and liver ablation. In 2019, fine-needle aspiration of a supraclavicular lymph node confirmed metastatic PTC, and molecular profiling identified an in-frame CCDC6–RET fusion. Despite TSH suppression, disease progressed to RAI-refractory metastases. In 2020, PET/CT showed pulmonary, hepatic, and mediastinal involvement. By October 2025, FDG PET/CT demonstrated enlarging pulmonary and hepatic metastases, new bone lesions, progressive lymphadenopathy and bilateral pleural effusions suspicious for pleural carcinomatosis, with rising thyroglobulin and thyroglobulin antibody blood levels.
Management and Outcome:
Given RET fusion positivity, progressive RAI-refractory disease, and limited systemic options, selpercatinib was initiated at a reduced dose of 40 mg daily. The patient is undergoing close monitoring for clinical response, tolerability, and disease control.

Conclusion: 
This case highlights an exceptionally rare RET fusion–positive PDTC in a nonagenarian and demonstrates the clinical value of molecular profiling in guiding targeted therapy. Although real-world evidence remains limited, this case suggests the feasibility and tolerability of selective RET inhibition in elderly patients with aggressive thyroid cancer.

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