SMARCA4-deficient Anaplastic Thyroid Carcinoma: A Hitherto Unreported Case

Loss of expression of TTF1 and PAX8 in primary thyroid malignancies raises concerns for metastatic disease in addition to a high-grade primary tumor. Precise distinction is critical, as treatment strategies differ. Herein, we present the case of a 74-year-old man with a right-sided neck swelling, and change in voice for 2 months. Clinically, a 6 cm restricted mobility mass involving thyroid was detected, which on CT scan showed abutment of trachea and esophagus, along with right cervical and upper-mediastinal lymphadenopathy.Biopsies from right thyroid lobe and right supraclavicular node showed an infiltrative carcinoma in nests and cords, a distinct squamoid appearance, focal rhabdoid morphology, extensive necrosis, and a desmoplastic stroma. Overt anaplasia was absent. Immunohistochemically, the tumor was positive for cytokeratins; negative for PAX8, TTF1, CK20, p63, p40, CDX2, SOX10, AR and synaptophysin; p53 showed wild-type staining. Further evaluation revealed retained SMARCB1 and complete loss of SMARCA4 (BRG1) expression in tumor cells. Lack of thyroid lineage markers prompted molecular profiling, and NGS revealed Pathogenic mutations in exon 3 of NRAS gene and exon 11 of BRAF gene (non BRAF v600E), consistent with a follicular thyroid carcinoma profile. Thus, a diagnosis of anaplastic thyroid carcinoma with SMARCA4 loss; likely arising from dedifferentiation of a follicular thyroid carcinoma, was made. The patient is on palliative chemotherapy, with progressive disease.SMARCA4-deficient carcinomas occur at various sites, de novo or as dedifferentiated carcinomas; hitherto unreported in thyroid. This case highlights the importance of integrating morphology, immunohistochemistry, and molecular testing in aggressive thyroid-associated carcinomas, with implications for diagnosis, prognostication, and targeted therapy.