A 35-year-old woman undergoes thyroidectomy for papillary thyroid carcinoma showing Orphan Annie eye nuclei, nuclear grooves, pseudoinclusions, and psammoma bodies. The most common molecular alteration in sporadic PTC is:

• A RAS mutation leading to follicular variant exclusively
• B PTEN mutation causing Cowden syndrome
• C RET/PTC rearrangement or BRAF V600E point mutation ✓
• D TP53 mutation characterizing undifferentiated (anaplastic) carcinoma

Explanation

Sporadic papillary thyroid carcinoma most commonly harbors BRAF V600E mutation (~60%) or RET/PTC rearrangements (especially post-radiation), both constitutively activating MAPK signaling. RAS mutations are more characteristic of follicular carcinoma and follicular variant PTC. PTEN mutations cause Cowden syndrome (follicular thyroid carcinoma). TP53 mutations are late events in anaplastic (undifferentiated) carcinoma progression.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.