A 55-year-old woman presents with a firm, painless thyroid mass and recent onset of watery diarrhea exceeding 1 liter per day. Serum calcitonin is 850 pg/mL. CEA is elevated. FNAC shows sheets of cells with amyloid staining on Congo red. Which genetic mutation is most likely to be found in this patient?
- A BRAF V600E point mutation
- B RET proto-oncogene mutation ✓
- C RAS point mutation
- D PAX8-PPAR gamma rearrangement
Explanation
This presentation is classic for medullary thyroid carcinoma: elevated calcitonin, watery diarrhea, amyloid on Congo red stain, and elevated CEA. MTC arises from parafollicular C cells. Approximately 25% of MTC cases are hereditary, associated with germline RET proto-oncogene mutations in the context of MEN2A, MEN2B or familial MTC. Even sporadic MTC frequently harbors somatic RET mutations. BRAF V600E is seen in papillary carcinoma. RAS mutations are seen in follicular carcinoma and some PTC variants. PAX8-PPAR gamma rearrangement is characteristic of follicular thyroid carcinoma.
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.