Deceptive Thyroid Pathologies: Anaplastic Thyroid Carcinoma Mimics and Clinical Implications

Beyond follicular-derived thyroid carcinomas, lymphomas, and metastatic disease, there are rare pathologies of the thyroid gland that represent a challenge. We report patients with unusual malignancies that mimic similar aggressive cancers.

Retrospective case series.

Eight patients with aggressive thyroid tumors presented with clinical and radiographic features concerning for anaplastic thyroid cancer (ATC). Three patients presumed to be diagnosed with Adamantinoma-like Ewing sarcoma (ALES), each harboring an EWSR1-FLI1 rearrangement. One patient with an enlarging neck mass was found to have osteoid-producing osteosarcoma. Another patient with a bulky neck mass and metastases demonstrated neolumen and ERG/CD31 positivity, confirming thyroid angiosarcoma. A separate patient was diagnosed with a high-grade sarcoma harboring a PRMT8-NTRK fusion, representing the first reported case. Two patients had mucoepidermoid carcinoma (MEC) variants-one classic MEC and one sclerosing MEC with eosinophilia (SMECE).

Multiple rare thyroid malignancies may present indistinguishably from ATC, emphasizing the need for meticulous histopathologic and molecular evaluation.