Clinicopathological features of sarcomatoid transformation in non-small cell lung cancer

In patients with driver gene-positive advanced non-small cell lung cancer (NSCLC), acquired resistance following targeted therapy remains a major clinical challenge. This resistance can arise through various mechanisms, such as point mutations, activation of bypass pathways, and transformation of cancer cells. Among these mechanisms, neuroendocrine differentiation is relatively common, whereas epithelial–mesenchymal transition (EMT) is also involved, though to a lesser extent. In contrast, sarcomatoid transformation is comparatively rare. In this study, we retrospectively analyzed eight patients with advanced NSCLC harboring driver gene mutations who developed sarcomatoid transformation after tyrosine kinase inhibitor (TKI) therapy at our hospital. We comprehensively examined their clinical characteristics, genomic profiles, and changes in the tumor immune microenvironment. Notably, paired PD-L1 testing revealed that all three evaluable cases showed increased PD-L1 expression after transformation, along with enhanced intratumoral lymphocyte infiltration in most patients. These findings provide valuable insights into the resistance mechanisms and potential therapeutic strategies for this challenging patient population.