A mediastinal lymph node sample from a patient with a history of breast cancer is tested to determine origin. Which panel would be most valuable?

• A. Napsin A +, GATA3 -
• B. GATA3 +, ER/PR/HER2(-/+)
• C. Napsin A +, TTF-1 +
• D. GATA 3+, Napsin A-

Answer: (B)

The key idea is using immunohistochemical profiles to identify where a metastatic tumor came from, especially distinguishing breast cancer from lung cancer in a lymph node sample. GATA3 is a sensitive marker for breast (and urothelial) carcinomas, so its positivity strongly supports a breast origin when metastasis is in doubt. Pairing GATA3 positivity with the breast-specific hormone receptor and HER2 status (ER/PR/HER2) gives a fingerprint that aligns with a patient’s known breast cancer and helps confirm that the mediastinal node metastasis is breast-derived rather than a primary lung tumor.

Markers like Napsin A and TTF-1 are more typical of lung adenocarcinoma; if those were positive, it would argue for a lung origin. In this case, the panel that shows GATA3 positivity with breast-related ER/PR/HER2 status is the most informative combination, since it both supports breast origin and helps rule out a lung source.