Neuroendocrine phenotype as an acquired resistance mechanism in ALK-rearranged lung adenocarcinoma

A 63-year-old caucasian woman, presenting with metastatic primitive lung adenocarcinoma was treated with ALK inhibitor crizotinib treatment for six month. After rapid regression of all known lesions, tumor progression appeared six month later on all the already known lesions. A biopsy of subclavicular lymphadenopathy revealed a carcinoma with neuroendocrine phenotype with both immunohistochemical expression of ALK protein and ALK-rearrangement. It was associated with acquired resistance to crizotinib with ALK-rearrangement but without point mutation or amplification of the ALK gene.We herein report the first case of histological neuroendocrine transformation after ALK inhibitor crizotinib treatment, associated with acquired resistance to crizotinib.