7012 Genetic Defects Involved in the Progression from Differentiated to Anaplastic Thyroid Cancer

Abstract Disclosure: S. Gill: None. L.F. Chavez: None. Although much more invasive and with a disease specific mortality approaching almost one hundred percent, anaplastic thyroid cancers (ATC) are not mutually exclusive from their differentiated counterparts. Almost one third of patients diagnosed with ATC have a coexisting synchronous differentiated thyroid carcinoma (DTC). We describe a case of a 59 year old male with a 20 pack year smoking history who presented to the hospital for dysphagia and dyspnea after a recent diagnosis of papillary thyroid carcinoma (PTC) one month earlier after workup for an enlarged thyroid. Patient was unfortunately lost to follow up after initial diagnosis. Notably, immunohistochemistry (IHC) was positive for PAX8, TTF1, and BRAF V600E at that time. On arrival to the emergency department, patient described the dysphagia as progressively worsening from solids to liquids associated with a 20 pound weight loss since initial diagnosis of PTC. He had also been experiencing hoarseness of voice, intermittent fevers, night sweats, and hemoptysis. Physical exam revealed an enlarged thyroid mass with discrete nodularity. Labs were largely unremarkable but CT imaging of the neck and chest revealed a heterogeneous mass 6.3 cm in diameter centered within the upper esophagus causing mass effect on the upper airway and scattered bilateral pulmonary nodules. The thyroid was also heterogeneous appearing and had multiple peripheral calcified masses along with a 4.2 cm hypodense nodule in the left lobe. Patient underwent tracheostomy to secure the airway along with laryngoscopy, thyroid biopsy, and esophagoscopy with biopsies. The results of the thyroid biopsy once again showed PTC while the results of the esophageal biopsies showed ATC. Given extensive metastases, the patient was deemed to have stage IVC ATC and he was started on palliative chemotherapy and radiation therapy. Treatment was switched to BRAF inhibition in the outpatient setting after documentation of BRAF V600E mutation in the ATC component. IHC also revealed expression of PAX8, p53, CAM 5.2, and vimentin within the ATC component. And so, just one month after initial diagnosis of PTC, the patient developed ATC in the surrounding thyroid. This case highlights how DTC can serve as a stepping stone for the development of ATC. The mechanism at play may be due to genetic defects such as those in BRAF V600E and PAX8 that could be seen in both the DTC and ATC possibly signifying an underlying unifying pathway. Presentation: 6/1/2024