An 82-year-old woman presents with a rapidly enlarging fixed anterior neck mass compressing the trachea, present for six weeks. Biopsy shows pleomorphic giant cells and spindle cells forming sarcoma-like sheets; residual well differentiated papillary carcinoma is identified adjacent to the lesion. Which molecular alteration is found in the majority of these tumors?

• A RET/PTC rearrangement
• B BRAF V600E mutation alone
• C RAS point mutation alone
• D TP53 mutation ✓

Explanation

Anaplastic carcinoma arises almost always from transformation of a pre-existing well differentiated thyroid cancer, as shown here by the adjacent papillary focus. Inactivating mutations of TP53 are present in the majority of anaplastic carcinomas and are thought to underlie the dedifferentiation step. BRAF V600E may coexist as the initiating lesion inherited from the papillary precursor, but BRAF or RAS alteration alone does not explain the anaplastic phenotype, making TP53 the answer asked for.

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.