MON-396 - Aggressive Metastatic Papillary Thyroid Carcinoma with Brain Involvement Associated with BRAFV600E and TERF1 Mutations: A Case Report

Background:
Papillary thyroid carcinoma (PTC) is typically associated with an excellent prognosis; however, a subset of patients develop aggressive disease with early distant metastases and poor outcomes. Molecular alterations such as BRAFV600E are associated with aggressive tumor behavior, radioiodine (RAI) refractoriness, and increased mortality. The clinical significance of TERF1 (telomeric repeat binding factor 1) mutations in thyroid cancer remains poorly defined. We report a case of widely metastatic PTC associated with concurrent BRAFV600E and TERF1 mutations.

Case Presentation:
A 54-year-old man presented to the ED in September 2024 with acute chest pain after minimal trauma and a two-year history of voice changes. CT imaging revealed multiple pulmonary nodules and widespread osseous lesions. Biopsy of a rib lesion confirmed metastatic thyroid carcinoma, and genomic profiling identified BRAFV600E and TERF1 mutations. Thyroid ultrasound demonstrated a 1.5 cm TI-RADS 5 nodule. He underwent total thyroidectomy with central and right lateral neck dissection, revealing bilateral multifocal PTC (0.2–1.6 cm) without extrathyroidal extension but with lymphovascular invasion and nodal metastases (10/60 nodes; largest 2.3 cm).

The patient received palliative radiation to the spine and sacrum. In May 2025, he developed an intracranial hemorrhage due to brain metastasis, requiring craniotomy, followed by partial brain radiation. He had not yet received RAI and was maintained on liothyronine by his previous endocrinologist, resulting in markedly elevated TSH level at 54 and a thyroglobulin level >3200 ng/mL. He was clinically neurologically intact on evaluation.

The case was discussed at a multidisciplinary tumor board. RAI with dexamethasone pretreatment due to central nervous system metastases is planned; however, given the extent of disease, RAI is not expected to be curative, and systemic therapy is anticipated. Aggressive TSH suppression with levothyroxine, in place of liothyronine, and PET/CT imaging are also planned.

Discussion

This case illustrates an unusually aggressive course of PTC with early and widespread metastases, including bone and brain involvement, despite small primary tumors. These findings highlight the potential synergistic role of BRAFV600E and TERF1 mutations in promoting metastatic behavior. Further studies are needed to clarify the prognostic and therapeutic implications of TERF1 mutations in differentiated thyroid carcinoma.

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