Histologic transformation of ALK-rearranged adenocarcinoma to squamous cell carcinoma after treatment with ALK inhibitor.

Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) treated with ALK tyrosine kinase inhibitor (TKI) eventually acquires resistance to the treatment. However, our current knowledge regarding the resistance mechanisms is based on non-synonymous mutation and amplification in ALK, with the reasons still unknown for nearly half of all such cases. Other than genomic alteration as a resistance mechanism, up to 10% of NSCLC with activating epithelial growth factor receptor (EGFR) mutation showed resistance to EGFR TKI through histologic transformation. Although limited in number, there are cases showing transformed samples retaining the initial genomic alteration, which support lineage transition as a novel resistance mechanism. In this report, we described the first case of squamous cell carcinoma (SCC) transformation from adenocarcinoma (ADC) in NSCLC with ALK rearrangement after treatment with ALK TKI.