Which panel would be most informative to confirm breast origin if analyzing mediastinal lymph node metastasis?

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

Answer: (B)

When determining the origin of a mediastinal metastasis, immunohistochemical panels guide you by highlighting markers typical for each tissue. GATA3 is a strong indicator of breast origin, as it is frequently expressed in breast carcinomas and is less common in primary lung cancers. On the other hand, Napsin A and TTF-1 are markers that more commonly point to lung adenocarcinoma when they are positive.

So a panel that shows GATA3 positivity along with estrogen receptor, progesterone receptor, and/or HER2 status (even if some of those receptors are negative) provides a clearer link to breast carcinoma. The presence of GATA3 plus a breast-receptor phenotype makes breast origin more likely than lung origin, because lung markers would be expected to be positive if the metastasis were from the lung.

In contrast, panels that emphasize lung markers—such as Napsin A or TTF-1 positivity—would steer you toward a pulmonary source, which is less consistent with a breast-derived metastasis. A panel with GATA3 positive but lacking additional breast-receptor information still supports breast origin, but combining GATA3 with the receptor profile provides stronger, more specific confirmation.