Histological transformation of ALK rearranged adenocarcinoma into small cell lung cancer: A new mechanism of resistance to ALK inhibitors

- Resistance to ALK tyrosine kinase inhibitors is common.
- Main resistances: gatekeeper mutation, bypass signaling, ALK amplification.
- ALK translocation is exceptional in primitive SCLC.
- SCLC transformation is a known resistance mechanism to EGFR TKI.
- SCLC transformation is uncommon in ALK rearranged adenocarcinoma.

Various mechanisms of resistance to ALK inhibitors in ALK rearranged adenocarcinomas are reported including secondary gatekeeper mutations, bypass signaling or ALK amplifications as the commonest ones. We report a new mechanism of resistance with transformation of adenocarcinoma into small cell lung cancer. A 53-year-old non-smoker woman, experienced cancer progression after two lines of ALK inhibitors. A new biopsy showed a small cell lung cancer. FISH revealed persistent ALK rearrangement with an atypical pattern and complete loss of the 5′ region of the ALK gene.