A 74-year-old man has a rapidly enlarging, fixed thyroid mass with hoarseness and stridor. Biopsy shows sheets of highly pleomorphic giant cells and spindle cells with numerous mitoses; immunostains are negative for thyroglobulin. Which molecular alterations best characterize this tumor?

• A RET/PTC rearrangement alone
• B RAS mutation alone
• C TP53 mutation frequently combined with TERT promoter mutation ✓
• D BRAF V600E mutation alone

Explanation

Anaplastic thyroid carcinoma arises through dedifferentiation of pre-existing well-differentiated carcinoma and characteristically accumulates TP53 mutations, often together with TERT promoter mutations, which drive its aggressive behavior. BRAF V600E or RAS mutations may be retained from the precursor tumor but are insufficient alone to explain anaplastic transformation. Negative thyroglobulin staining confirms loss of differentiation and excludes poorly differentiated follicular-derived tumors that retain marker expression.

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.