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.
Yanina Nikolaus (Mon,) studied this question.