Which two immunohistochemical markers would indicate a primary lung adenocarcinoma?

• A. Napsin A and p63
• B. Synaptophysin and chromogranin
• C. p63 and TTF-1
• D. TTF-1 and Napsin A

Answer: (D)

Immunohistochemical markers help reveal where a tumor started. TTF-1 is a nuclear protein expressed in lung and thyroid epithelium, and in lung cancers it is most commonly positive in adenocarcinoma, signaling a pulmonary origin. Napsin A is a cytoplasmic enzyme present in type II pneumocytes and is positive in most lung adenocarcinomas while being negative in squamous cell carcinomas. When both TTF-1 and Napsin A are positive, it strongly supports a primary lung adenocarcinoma rather than a metastasis from another site or a different histology.

Neuroendocrine markers like synaptophysin and chromogranin point toward neuroendocrine tumors, not adenocarcinoma. p63 highlights squamous differentiation, which argues against adenocarcinoma. So the combination of TTF-1 and Napsin A is the most specific for primary lung adenocarcinoma.