Napsin-A Immunohistochemistry in the Diagnosis of Pulmonary Alveolar Proteinosis

The diagnosis of pulmonary alveolar proteinosis (PAP) relies on a limited set of stains, namely hematoxylin-eosin and periodic acid-Schiff-diastase (PAS-D), demonstrating abundant alveolar material representing mostly surfactant. As cells harboring surfactant also express Napsin-A (pneumocytes and macrophages), we hypothesized that it would also be expressed within alveoli in PAP.

To evaluate the sensitivity and specificity of Napsin-A in the diagnosis of PAP.

A 12-year retrospective case control study was designed to identify cases of PAP and potential histologic mimics (intra-alveolar fibrin, pulmonary edema, diffuse alveolar damage, and alveolar mucinosis). PAS-D staining and Napsin-A immunohistochemistry were performed. Distribution and intensity were evaluated by using a semiquantitative 3-point scale. Positivity was defined as 2+ intensity score, regardless of distribution.

Eleven cases of PAP and 46 control cases were identified. Napsin-A showed positivity in all PAP cases and 3 of 12 cases of edema. Among positive cases, all those with a 2+ distribution were PAP cases, with heterogeneous (1+) staining in all cases of edema. PAS-D showed positivity in all cases of PAP and most controls, except cases of edema. Sensitivity and specificity of Napsin-A for PAP were 100% and 94%, respectively, and of PAS-D for PAP, 100% and 21%, respectively. Double positivity for Napsin-A and PAS-D was 100% specific and sensitive for PAP.

This study is the first to demonstrate that Napsin-A is highly specific for the diagnosis of PAP, more so than PAS-D. It also shows that the combined positivity of Napsin-A and PAS-D is 100% specific and sensitive for PAP.