Dr. Nelson Ordonez (MD Anderson Cancer Center, Houston) published a brief and very helpful article in the March 2012 American Journal of Surgical Pathology (abstract) that addresses a very practical issue of using IHC staining for Napsin A in evaluating primary lung NSCLC for confirmation of adenocarcinoma type.
Napsin A is normally expressed in type II alveolar pneumocytes but may also be localized immunohistochemically in intraalveolar macrophages presumably from phagocytosis. The expression of both Napsin A and pro-surfactant protein B (ProSP-B) are regulated by thyroid transcription factor-1 (TTF-1), which is one of the common IHC stains initially performed on NSCLC not diagnostic for adenocarcinoma on routine H&E. Napsin A is localized to lamellar bodies with ProSP-B and is thought to be involved in post-translational processing of ProSP-B.
This paper must be understood in the context of new IASLC lung adenocarcinoma classification and the algorithm recommended to histological type NSCLC. Napsin A has emerged as a useful adjunct IHC stain, such as, in those cases in which a tumor is negative or equivocal for initial screening markers for both adenocarcinoma (ADC) and squamous cell carcinoma (SQC). Until recently, Napsin A was found to be highly specific for lung ADC. But, as Dr. Ordonez points out, several recent publications have found Napsin A positivity in lung squamous cell carcinomas and, thus, cast doubt over the high degree of specificity of Napsin A for lung adenocarcinoma and utility of this marker in this context.
Dr. Ordonez studied Napsin A expression by IHC in 90 primary lung SQC, including whole section and biopsy specimens, and 64 non-pulmonary SQC. None of the primary lung SQC or the non-pulmonary SQC showed Napsin A positive staining in the malignant cells.
The key observation is the identification of entrapped type 2 pneumocytes and/or intraalveolar macrophages in desmoplastic areas adjacent to the tumor and in small clusters within the tumor--which could be a source of false-positive interpretation in SQC. Dr. Ordonez found 5 biopsies in which these entrapped cells were difficult to distinguish from malignant cells and CK 5/6 was used in 2 of these cases to rule out the possibility that these were Napsin A-positive malignant squamous cells.
This is a critical distinction and very welcome contribution to the lung cancer pathology literature. The reader should keep point this in mind, especially when evaluating biopsy material. The illustrations are excellent in demonstrating these points and should also be kept close at hand. Congratulations to Dr. Nelson Ordonez for an excellent paper.