To the Editor.—I read with great interest the 2 articles authored by Whithaus et al1 and Turner et al.2 In our department, a large number of lung tumors are diagnosed annually. Most of the tumors are adenocarcinoma, and an accurate diagnosis is critical because we routinely perform EGFR mutation analysis on these cases. We rely on TTF1 (thyroid transcription factor 1) primarily as a diagnostic marker and have been using napsin A when TTF1 results are negative, weak, or inconclusive, for example, with poorly differentiated adenocarcinoma. Napsin A has also been useful in cases where the tumor is diffusely positive for both TTF1 and p63.
Interpretation of napsin A is relatively difficult because it is a cytoplasmic stain, and weak staining of macrophages within the tumor may cause difficulties in interpretation. One pitfall in the immunohistochemistry of lung tumors is the nonspecific staining of entrapped, nonneoplastic lung epithelium within tumor, which can be stained by both TTF1 and napsin A.3
The role of napsin A as a diagnostic marker for metastatic lung tumors is complicated by contradictory reports on its sensitivity or specificity compared with TTF1. However, those studies were performed with much smaller series.2,4 We had one case where the metastatic tumor was TTF1− but expressed napsin A. Finally, the workup led to the diagnosis of metastatic renal cell carcinoma. Therefore, napsin A should be used as part of a larger panel of immunohistochemical stains in such cases.