p53-Mutant Biphenotypic Non-Small Cell Lung Carcinoma with Coexpression of TTF-1 and p40: A Distinct Histopathologic Entity? A Case Report and Literature Review

In non-small cell lung carcinoma (NSCLC), TTF-1 and p40 are well-established immunohistochemical markers for the separation of adenocarcinoma from squamous cell carcinoma. These markers typically occur in distinct and separate tumor types; however, TTF-1 and p40 coexpression has been increasingly documented in recent years. Such tumors usually exhibit a basaloid cellular architecture, with the same neoplastic cells showing diffuse nuclear positivity for both markers. Molecular studies often detect mutations in TP53 as the main alteration in these tumors. Several reported cases have demonstrated aggressive behavior and have been associated with poor outcomes. The coexpression of TTF-1 and p40 may reflect a dual cell differentiation process driven by alterations in the p53 signaling pathway. Recent studies suggest that these tumors represent a distinct subtype of NSCLC within the current WHO and IASLC classification systems. Here, we present a rare case of TP53-mutant NSCLC exhibiting coexpression of TTF-1 and p40.