Rare transformation from small cell lung cancer to lung squamous cell carcinoma: a case report

Despite the evolution of treatment for extensive-stage small cell lung cancer (ES-SCLC) and advanced non-small cell lung cancer (NSCLC), drug resistance remains a major clinical challenge. Histological transformation is one of the key mechanisms. Previous studies mostly reported transformation from NSCLC to SCLC. Here we reported a patient with lung squamous cell carcinoma transformation from SCLC after multiple lines of treatment. A 60-year-old male patient was diagnosed with ES-SCLC (cT4N3M1a) in October 2022. In addition to first-line chemotherapy, immunochemotherapy with or without anti-angiogenic agent was used in the subsequent treatment lines. Given the elevation of squamous cell carcinoma markers during third-line treatment, the patient underwent the second biopsy. The pathological examination showed transformation from SCLC to lung squamous cell carcinoma, which was confirmed by the third biopsy. Finally, the patient died due to ‌acute massive cerebral infarction on November 30, 2025, which was unrelated to treatment or cancer. This rare case highlights the importance of re-biopsy during the disease course, especially for patients with poor response. We hope that this case can provide reference for physicians in clinical practice.