A 68-year-old woman reports a rapidly enlarging anterior neck mass over six weeks, with hoarseness, dysphagia and stridor. The mass is hard and fixed. FNA shows sheets of highly pleomorphic giant cells and spindle cells with numerous mitoses; immunostains are negative for thyroglobulin. The most frequent molecular alteration in this tumour is:

• A TP53 mutation ✓
• B RET/PTC rearrangement
• C RAS point mutation as the sole driver
• D MEN1 gene mutation

Explanation

Anaplastic thyroid carcinoma occurs in the elderly, grows explosively with local invasion causing hoarseness and stridor, and is composed of undifferentiated pleomorphic giant and spindle cells that lose thyroglobulin expression. Inactivation of TP53 is the most frequent alteration and is thought to underlie progression from a pre-existing differentiated carcinoma. RET/PTC and RAS are drivers of papillary and follicular tumours respectively, while MEN1 mutation is unrelated.

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.