The expression of Napsin A by immunohistochemistry in colorectal adenocarcinomas: An observational study

Background: Distinguishing primary colorectal adenocarcinoma from metastatic pulmonary adenocarcinoma can be challenging in small biopsies, particularly when tumors are mucin-rich or poorly differentiated. Napsin A is widely used as a marker of pulmonary adenocarcinoma, yet scattered reports suggest it may sometimes be expressed in non-pulmonary primaries, including colorectal cancer. We set out to see how often napsin A is expressed in colorectal adenocarcinomas in our setting and to gauge how much of a diagnostic trap it may pose. Methods: We retrospectively reviewed 107 colorectal adenocarcinoma samples using formalin-fixed, paraffin-embedded tissue blocks. Napsin A immunohistochemistry was performed using polyclonal and monoclonal antibodies. Three pathologists independently reviewed the slides; napsin A was considered positive when granular cytoplasmic staining was present in at least 1% of tumor cells. For each case, we recorded tumor differentiation, histological subtype, and CDX2 status. Results: Of the 107 tumors, 83 (77.6%) were moderately differentiated, 18 (16.8%) poorly differentiated, and 6 (5.6%) well differentiated. Histological subtypes included not otherwise specified (84.1%), mucinous (6.5%), signet ring (6.5%), and a small number of other variants. All cases were CDX2 positive, supporting a colorectal origin. Napsin A staining was observed in only 1/107 cases (0.9%) of poorly differentiated signet-ring adenocarcinoma, confined to the monoclonal antibody; none showed positivity with the polyclonal antibody. Conclusion: In this series, napsin A expression in colorectal adenocarcinoma was uncommon but not absent. Thus, a napsin A-positive metastatic adenocarcinoma could still represent a colorectal primary, especially in unusual histological subtypes. Our findings support cautious use of napsin A, always alongside morphology, a broader immunohistochemical panel, clinical data, and, where possible, molecular work-up. A larger multicenter dataset would help clarify generalizability and whether specific colorectal carcinoma subtypes are more prone to napsin A expression.