A 45-year-old man with MEN2A syndrome undergoes prophylactic thyroidectomy. Histology reveals medullary thyroid carcinoma (MTC). Immunohistochemistry would be POSITIVE for which combination of markers, confirming the diagnosis?
- A Thyroglobulin, TTF-1, and PAX8 — confirming follicular cell origin
- B CD56 and synaptophysin with CK20 positivity — confirming Merkel cell carcinoma pattern
- C EBER (ISH), CD20, and BCL-6 — confirming lymphoma in the thyroid
- D Calcitonin, CEA, chromogranin A, and synaptophysin — confirming parafollicular C-cell origin ✓
Explanation
Medullary thyroid carcinoma arises from calcitonin-secreting parafollicular C-cells. Its IHC profile includes: calcitonin (highly specific, diagnostic), CEA (carcinoembryonic antigen — elevated serum CEA is a prognostic marker), and neuroendocrine markers (chromogranin A, synaptophysin, CD56). TTF-1 is often positive (shared with lung and thyroid) but thyroglobulin and PAX8 are NEGATIVE (C-cells do not synthesize thyroglobulin). Congo red staining of the stroma may show amyloid (from misfolded calcitonin). In MEN2A, activating RET proto-oncogene mutations (codon 634 most common) drive MTC.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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