The Role of Napsin A, Caveolin-1, Type III Collagen and Tenascin-X Immunohistochemical Markers in the Differential Diagnosis of Primary Lung Adenocarcinomas and Pleural Epithelioid Mesotheliomas

The differential diagnosis between pleural epithelioid mesothelioma and peripheral lung adenocarcinoma remains a significant diagnostic challenge for pathologists. This study aimed to evaluate the diagnostic efficacy of a multi-antibody immunohistochemical (IHC) panel comprising Napsin A, Caveolin-1, Type III Collagen, and Tenascin-X. While Napsin A and Caveolin-1 are established markers, the diagnostic utility of Tenascin-X and Type III Collagen remains less explored in the current literature. A retrospective IHC analysis was performed on 70 paraffin-embedded tissue blocks, comprising 35 lung adenocarcinomas and 35 epithelioid mesotheliomas, diagnosed between 2005 and 2014. The expression patterns of Napsin A, Caveolin-1, Type III Collagen, and Tenascin-X were evaluated and compared between the two groups. Napsin A showed high sensitivity for adenocarcinoma (94.3%) with minimal expression in mesothelioma (2.9%). Conversely, Caveolin-1 and Tenascin-X emerged as strong markers for mesothelioma, with positivity rates of 97.2% and 88.6%, respectively (p < 0.001). Although Type III Collagen was exclusively expressed in mesothelioma (17.1%) and absent in all adenocarcinoma cases, its low sensitivity limits its standalone utility. Significant statistical differences were observed between the two tumor types for all markers evaluated. Our findings suggest that a panel including Napsin A, Caveolin-1, and Tenascin-X significantly aids in the differential diagnosis of lung adenocarcinoma and epithelioid mesothelioma. While Tenascin-X provides valuable supplementary data, the clinical application of Type III Collagen is constrained by its low sensitivity. Integrating these markers into diagnostic protocols can enhance diagnostic accuracy, though further validation in larger cohorts is recommended.