Transformation of ALK-translocated lung adenocarcinoma to LCNEC under alectinib treatment - a case report and mini-review.

The histologic transformation of non-small-cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) alterations remains a rare phenomenon and a challenge for treatment with ALK tyrosine kinase inhibitors (TKI). We present a seldom-reported case of transformation of lung adenocarcinoma into large-cell neuroendocrine carcinoma (LCNEC) during treatment with alectinib, a second-generation ALK inhibitor, aiming to evaluate diagnostic and therapeutic approaches. The underlying mechanisms driving this transformation-likely due to a secondary resistance mechanism acquired during treatment-remain poorly understood but may involve genetic alterations, changes in the tumor microenvironment, and the emergence of additional oncogenic mutations. This case adds to the limited body of evidence and underscores the importance of recognizing neuroendocrine differentiation in ALK-positive lung cancer cases that show clinical progression. Further studies are needed to elucidate the molecular drivers of this transformation and to optimize treatment strategies for affected patients.