A 60-year-old man with a peripheral lung adenocarcinoma is found to have an EGFR exon 19 deletion by molecular testing. Which IHC marker is most useful to confirm the diagnosis of lung adenocarcinoma (as opposed to squamous cell carcinoma) and direct targeted therapy selection?

• A p40 and CK5/6 positivity
• B CD56 and synaptophysin positivity
• C Calretinin and WT-1 positivity
• D TTF-1 and Napsin A positivity ✓

Explanation

TTF-1 (thyroid transcription factor-1) and Napsin A are the key IHC markers for lung adenocarcinoma — TTF-1 is expressed in ~75-80% of lung adenocarcinomas and is required for EGFR mutation testing interpretation in clinical practice. p40 (best squamous marker, superior to p63) and CK5/6 mark squamous cell carcinoma. CD56 and synaptophysin mark neuroendocrine tumors. Calretinin/WT-1 are used for mesothelioma. Correct subtype assignment is essential because EGFR/ALK/ROS1 targeted therapies apply specifically to adenocarcinoma.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.