Differentiating squamous cell carcinoma from adenocarcinoma (ACA) in cytology specimens can be challenging. Recent literature showed p40 had higher specificity than p63 for this purpose.
We identified 190 cytology cases with p40 (polyclonal) and p63 (monoclonal clone 4A4) immunohistochemistry, including specimens from fine-needle aspirations (FNAs) and effusions.
ACAs of lung origin stained for p40 and p63 in 21% and 20% of cases, respectively, regardless of specimen site. Among lung FNAs of primary pulmonary ACAs (n = 42), 14% were positive for p40 and 24% were positive for p63. Of the 20 pulmonary ACAs in effusions, more cases showed p40 positivity (40%) compared with FNAs, whereas p63 were positive in 15%. Among metastatic ACAs from other sites (n = 14), more cases were positive for p40 than p63.
Polyclonal p40 yields a level of false positivity in ACAs similar to p63, which is highest in effusions and is not limited to lung origin.