SUN-337 Aggressive Papillary Thyroid Carcinoma with Miliary Pulmonary Metastases and Unconventional Treatment Adaptations

Abstract Disclosure: J.B. Ding: None. R. Pristoop: None. M.L. Pierce: None. A. Holley: None. O.O. Tannous: None. I.G. Veytsman: None. A. Omogbehin: None. D. Moreno Watashi: None. K.D. Burman: None. Introduction or Background: Papillary thyroid carcinoma (PTC) is typically an indolent, localized disease. This report details a highly aggressive case of PTC presenting with extensive lung and skeletal metastases in a 48-year-old male, delineating its unusual progression and therapeutic responses. Clinical Case: A 48-year-old male with hypertension and obstructive sleep apnea presented with a five-week history of a non-productive cough and a rapidly enlarging left cervical mass. Laboratory tests showed suppressed TSH (<0.008 U/L, normal range: 0.450 to 4.500 U/L), elevated free T3 (9.59 pg/mL, normal range: 2.30 to 4.20 pg/mL), and free T4 levels (2.17 ng/dL, normal range: 0.82 to 1.77 ng/dL). Imaging revealed diffuse miliary and nodular pulmonary disease, extensive lymphadenopathy, and skeletal metastases. Fine needle aspiration of a cervical lymph node confirmed PTC.He was started on methimazole (20mg daily) and propranolol (40mg three times daily) before undergoing total thyroidectomy with bilateral neck dissection. Pathology revealed extensive vascular and esophageal invasion, with 33 out of 88 lymph nodes positive for metastatic disease. Postoperatively, he received palliative radiation (3000 cGy over 10 sessions) targeting T8-T10 for pain control and structural stabilization. However, two weeks later, worsening spinal constriction at the radiation site necessitated urgent T7-T11 laminectomy. He then received radioiodine ablation with 300 mCi of I-131. Molecular profiling identified aggressive BRAF (G4668/V, G4698/R/V in exon 11) and TP53 (pN235Y) mutations. This genetic profile led to an unconventional treatment protocol aimed at redifferentiation therapy to enhance iodine uptake in metastatic sites. Notably, trametinib was first started, which was later switched to lenvatinib due to nephrotoxicity. Post-ablation imaging indicated increased iodine uptake, and his urine iodine levels decreased from 395 mcg/L to 106 mcg/L, indicating partial restoration of iodine-absorbing ability in metastatic sites. Despite extensive pulmonary involvement, pulmonary function tests remained stable, showing mild obstruction attributed to childhood asthma rather than thyroid cancer.Seven months post-discharge, TSH stabilized at 3.0 U/L, thyroglobulin antibody levels were < 1.0 U/mL, and free T4 remained at(0.7 ng/dL. The patient continues home-based supportive care with no significant symptoms. Clinical Lessons or Conclusions: This case highlights the potential for highly aggressive PTC, particularly with BRAF and TP53 mutations. Molecular profiling guided redifferentiation therapy and targeted interventions, underscoring the importance of genetic insights in managing atypical thyroid cancer. Personalized medicine, adapting treatments based on genetic insights and patient tolerance, plays a crucial role in optimizing outcomes in advanced PTC. Presentation: Sunday, July 13, 2025