SUN-316 A Case of Anaplastic Thyroid Carcinoma That Presented as Metastatic Disease of Unknown Primary

Abstract Disclosure: A.C. Rios Chen: None. Z. Arter: None. Y. Haidar: None. Q. Ho: None. A. Mohyeldin: None. J. Dai-Ju: None. Background: Anaplastic thyroid carcinoma (ATC) is a highly aggressive cancer whose diagnosis is known to be notoriously difficult, especially in cases with widespread metastases, where overlapping features with other poorly differentiated carcinomas may obscure the primary site. Clinical Case: A 78-year-old male presented with an incidental finding of multiple bilateral pulmonary nodules on chest CT. PET/CT revealed metastases in the lung, bone, as well as FDG uptake in the left thyroid lobe. A bone biopsy at an outside institution identified metastatic adenocarcinoma of unknown primary, initially suspected to be of pulmonary origin. A follow-up CT revealed a 3.2 cm left thyroid lesion with mild tracheal compression, right paratracheal and cervical lymphadenopathy. Fine needle aspiration (FNA) of the thyroid nodule was positive for anaplastic thyroid carcinoma. Based on positive staining for PAX8, pathology review of bone biopsy slides at our institution ruled out lung carcinoma and confirmed thyroid as the primary site. Molecular testing was not performed due to insufficient tissue. Brain MRI found multiple brain metastases, most less than 2 cm in size. Bloodwork showed normal thyroid function, with Thyroglobulin (Tg) 1,619.5 ng/mL (Quest LC/MS) (2.8-40.9 ng/mL), Tg antibodies 53 (< 1 IU/mL). Given the aggressive nature of the disease, a liquid biopsy identifying BRAF V600E prompted immediate initiation of dabrafenib-trametinib therapy. Follow-up imaging one month later showed substantial reductions in brain metastases sizes and perilesional edema of the right parietal lobe lesion. Stereotactic radio therapy for brain metastasis was deferred. Interval PET/CT also exhibited decrease of tumor size and FDG uptake. The patient is pending total thyroidectomy. Conclusion: ATC can be a significant diagnostic challenge and often requires thorough pathologic evaluation with targeted immunohistochemistry. Early identification of targetable somatic mutations can significantly aid selection of effective therapy. In this case, a therapy of dabrafenib and trametinib achieved a highly favorable outcome for BRAF-positive ATC. References: Bible KC, Kebebew E, et al. 2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer. Thyroid. 2021 Mar;31(3):337-386. doi: 10.1089/thy.2020.0944. Erratum in: Thyroid. 2021 Oct;31(10):1606-1607. doi: 10.1089/thy.2020.0944.correx. PMID: 33728999; PMCID: PMC8349723. Keywords: anaplastic thyroid carcinoma Presentation: Sunday, July 13, 2025