p40-positive metastatic urothelial carcinoma mimicking primary pulmonary squamous cell carcinoma on limited lung biopsy

A man in his early 70s with a prior history of high-grade urothelial carcinoma presented with a large left upper lobe lung mass detected on imaging. Endobronchial biopsy demonstrated non-small cell carcinoma with squamoid morphology and diffuse p40 positivity, supporting an initial diagnosis of primary pulmonary squamous cell carcinoma. The patient received neoadjuvant platinum-based chemotherapy and immunotherapy without a significant radiographic response. Subsequent lobectomy revealed a carcinoma with prominent papillary architecture and an immunophenotype characterised by cytokeratin 7, cytokeratin 20, GATA binding protein 3 (GATA3) and p40 positivity, supporting metastatic urothelial carcinoma. Review of the original biopsy confirmed limited tissue with overlapping squamoid features. This case highlights a potential diagnostic pitfall: metastatic urothelial carcinoma may demonstrate diffuse p40 expression and mimic primary pulmonary squamous cell carcinoma on limited lung biopsy, emphasising the importance of expanded immunohistochemical panels and clinicopathologic correlation.