A 68-year-old woman reports rapid enlargement of a long-standing neck swelling over three months, now causing stridor and hoarseness. Examination shows a hard, fixed thyroid mass with cervical lymphadenopathy. Biopsy reveals sheets of highly pleomorphic giant cells and spindle cells with numerous atypical mitotic figures; immunostains are negative for thyroglobulin and calcitonin, and positive for pancytokeratin focally. The most likely diagnosis is:
- A Medullary thyroid carcinoma, small cell variant
- B Primary thyroid lymphoma arising in Hashimoto thyroiditis
- C Metastatic renal cell carcinoma to the thyroid
- D Anaplastic (undifferentiated) thyroid carcinoma arising from a pre-existing differentiated carcinoma ✓
Explanation
Rapidly growing fixed thyroid mass in an elderly patient with pleomorphic giant and spindle cells is anaplastic carcinoma, one of the most aggressive human malignancies. It frequently arises by dedifferentiation of a pre-existing papillary or follicular carcinoma, often with TP53 mutations alongside retained BRAF or RAS alterations. Calcitonin negativity excludes medullary carcinoma, whose cells are also neuroendocrine marker positive. Thyroid lymphoma occurs in Hashimoto disease but consists of monotonous lymphoid cells, not pleomorphic giant cells, and is CD20 positive.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.