EP964 - ECE_3035 - SMARCA4-Mutated Anaplastic Thyroid Carcinoma in a Young Adult: First Reported Case.

Abstract

Anaplastic thyroid carcinoma (ATC) is a rare and highly aggressive thyroid malignancy,affecting elderly patients. Although molecular profiling has become increasingly important in ATC, alterations of the SWI/SNF chromatin-remodelling complex, including SMARCA4 mutations, have not previously been reported in this tumour type. A 31-year-old male with no significant medical history presented with a rapidly enlarging neck mass, progressive dyspnoea and reduced exercise tolerance over approximately six weeks. Neck ultrasound revealed a large, heterogeneous, infiltrative tumour of the left thyroid lobe causing significant tracheal compression and associated cervical lymphadenopathy. Fine-needle aspiration biopsy showed malignant cells (Bethesda category VI) with suspicion of ATC; however, given the patient's young age, thyroid lymphoma was also considered. Core-needle biopsy with extensive immunohistochemical and molecular analyses excluded lymphoma, melanoma, sarcoma and NUT carcinoma, establishing the diagnosis of anaplastic thyroid carcinoma with a SMARCA4 mutation. Staging computed tomography demonstrated stage IVB disease with extensive locoregional invasion and massive venous thrombosis extending from the right atrium to both internal jugular veins. The patient was not eligible for surgical or radiotherapeutic treatment. Therapeutic anticoagulation and systemic glucocorticoids resulted in transient clinical improvement. Rapid disease progression led to airway compromise requiring tracheal stenting, followed by initiation of palliative chemotherapy with carboplatin and paclitaxel. SMARCA4 alternations is a recognised drivers of several aggressive undifferentiated malignancies and is associated with rapid progression and poor prognosis. Its identification in ATC expands the molecular spectrum of this disease and may explain the unusually young age at presentation and aggressive clinical course. To our knowledge, this is the first reported case of SMARCA4-mutated anaplastic thyroid carcinoma. The case highlights the importance of comprehensive molecular profiling in ATC, particularly in young patients or those with atypical clinical features, to improve diagnostic accuracy and inform future therapeutic strategies.