Papillary thyroid carcinoma (PTC) has the characteristic nuclear features known as 'Orphan Annie eye' nuclei. At the molecular level, the most common oncogenic driver event in PTC is:

• A RAS mutation causing follicular pattern PTC
• B PAX8-PPARG rearrangement
• C BRAF V600E point mutation (~60%) or RET/PTC rearrangements (~20%) ✓
• D TERT promoter mutation as initiating event

Explanation

BRAF V600E is the most common single molecular event in PTC (~60% of cases), constitutively activating MAPK/ERK signaling. RET/PTC chromosomal rearrangements (RET/PTC1 = t(10;10), inv; RET/PTC3 = t(10;17)) are found in ~20% and are especially prevalent in radiation-induced PTC. Both activate the same MAPK pathway. BRAF V600E correlates with classical PTC, extrathyroidal extension, lymph node metastasis, and higher recurrence risk. RAS mutations are more common in follicular thyroid carcinoma. PAX8-PPARG rearrangement characterizes follicular thyroid carcinoma. TERT promoter mutations are secondary events associated with dedifferentiation and poor prognosis.

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

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Written and medically reviewed by the StethoPrep medical team.