A 40-year-old woman with a thyroid nodule undergoes fine-needle aspiration cytology. Cytology shows ground-glass 'Orphan Annie eye' nuclei, nuclear grooves, and pseudoinclusions. BRAF V600E mutation is detected on molecular testing. What is the diagnosis and the mechanism by which BRAF V600E drives carcinogenesis?
- A Follicular thyroid carcinoma; BRAF V600E activates PI3K/AKT pathway via direct phosphorylation
- B Medullary thyroid carcinoma; BRAF V600E mimics calcitonin receptor signalling
- C Anaplastic thyroid carcinoma; BRAF V600E directly inhibits p53 nuclear export
- D Papillary thyroid carcinoma; BRAF V600E constitutively activates MEK/ERK MAPK pathway independent of upstream RAS activation ✓
Explanation
The cytological features (Orphan Annie eye nuclei, nuclear grooves, pseudoinclusions) are pathognomonic for papillary thyroid carcinoma (PTC). BRAF V600E (found in ~60% of PTCs) is a gain-of-function point mutation where valine is replaced by glutamate at codon 600, mimicking the phosphorylated activation loop conformation of BRAF and constitutively activating the RAF→MEK→ERK MAPK signalling cascade without requiring upstream RAS activation. This drives uncontrolled thyrocyte proliferation. BRAF V600E-mutant PTCs are associated with more aggressive behaviour, extrathyroidal extension, and reduced radioiodine uptake (downregulation of NIS).
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.