MON-411 - Rapid Dedifferentiation of Papillary Thyroid Carcinoma to Anaplastic Thyroid Carcinoma Despite Reassuring Molecular Testing: A Case Highlighting Diagnostic and Therapeutic Challenges.

Background
Papillary thyroid carcinoma (PTC) follows an indolent course. Rarely, PTC may dedifferentiate into anaplastic thyroid carcinoma (ATC), an aggressive malignancy with rapid progression and poor outcomes. Diagnostic delay may occur when cytology and molecular classifiers appear reassuring despite high-risk clinical and radiographic features.

Case Presentation
A 67-year-old man initially presented in September 2024, when a left posterior thyroid lesion was incidentally identified on chest computed tomography. Dedicated neck imaging demonstrated an infiltrative left thyroid mass measuring 3.5 × 2.1 cm, a suspicious left level IV lymph node measuring 2.6 × 1.9 × 2.0 cm, and left vocal cord paralysis.

Fine-needle aspiration demonstrated an indeterminate follicular neoplasm (Bethesda IV). Molecular testing using a genomic classifier was reported as benign. About 2 months from initial presentation, the patient underwent total thyroidectomy, with surgical pathology confirming papillary thyroid carcinoma.

Approximately 11 months from initial presentation, follow-up imaging demonstrated persistent cervical disease, and a modified left neck dissection was performed. Pathology demonstrated metastatic papillary thyroid carcinoma with extensive necrotic adenopathy and vascular invasion.

Approximately 14 months from initial presentation, the patient developed rapidly progressive neck swelling and left upper extremity pain. Imaging revealed a large infiltrative left supraclavicular mass encasing the common carotid artery, extensive mediastinal lymphadenopathy, lytic lesions of the cervical and thoracic spine, and bilateral pulmonary consolidations and micronodules, concerning for metastatic disease.

Biopsy of the supraclavicular mass and tracheal debridement demonstrated poorly differentiated carcinoma with extensive lymphatic invasion. Immunohistochemistry showed tumor cells positive for CK-Oscar and focal PAX8 and negative for thyroglobulin and TTF-1. Comparison with prior specimens confirmed identical malignant cells, consistent with dedifferentiation of papillary thyroid carcinoma into anaplastic thyroid carcinoma.
Next-generation sequencing identified a BRAF p.(V600E) c.1799T>A mutation, and targeted therapy with dabrafenib and trametinib was initiated.

Conclusion
This case demonstrates rapid dedifferentiation of papillary thyroid carcinoma into anaplastic thyroid carcinoma within approximately 14 months of initial presentation. Despite indeterminate cytology and benign molecular classifier results, high-risk features including infiltrative imaging, vocal cord paralysis, and aggressive lymphadenopathy should prompt early aggressive evaluation. Comprehensive molecular profiling remains critical, as identification of actionable mutations such as BRAF V600E may guide therapy, although prognosis remains poor.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*