Which pattern most strongly indicates a lung origin due to TTF-1 positivity?

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

Answer: (A)

TTF-1 positivity points to a pulmonary origin. TTF-1 is a nuclear transcription factor that is strongly associated with lung adenocarcinomas (and thyroid tumors), so when a tumor expresses TTF-1, it raises suspicion for a lung primary rather than a metastasis from many other sites. Napsin A supports this inference because it is commonly expressed in lung type II pneumocytes and is frequently positive in lung adenocarcinomas. Seeing both markers positive creates a pattern that is highly characteristic of a lung-origin tumor.

In contrast, GATA3 is a marker more typical of breast and urothelial carcinomas, so its positivity would steer away from a lung source even if TTF-1 is present in some contexts. ER/PR/HER2 status is used to characterize breast tumors, not lung tumors, so that pattern provides different directional information.

Thus, the combination of Napsin A positive and TTF-1 positive most strongly indicates a lung primary.