Histologic transformation of lung adenocarcinoma to squamous cell carcinoma after chemotherapy: two case reports

Squamous cell carcinoma (SCC) transformation of lung adenocarcinoma has been reported to take place after target therapy resistance. The patterns and mechanisms underlying this phenomenon needs to be explored. We present two such patients here. One patient complained of cough and hemoptysis, the other experienced chest tightness. Both were diagnosed as lung adenocarcinoma. They harbored no driver gene alterations and received first-line and adjuvant chemotherapy respectively. After progression several months later, the second biopsy revealed SCC transformation and the gene test still found no gene abnormalities. The diseases stayed stable after treatment of new therapeutic regimens. Then we searched for literature related and found SCC transformation happened at resistance to target therapy or immunotherapy or spontaneously. Our cases suggested this phenomenon could also happen at resistance to cytotoxic drugs. According to the reported cases, a new target therapy or chemotherapy might be effective after SCC transformation. The mechanisms underlying transformation have not been fully elucidated and probably relate to multiple genetic alterations and cancer stem cells. Since the SCC transformation could happen under various circumstances, we recommend lung cancer patients to run the second biopsy after progression and conduct gene tests to elicit the mechanisms.