A Case of EGFR Mutation-positive Non-small Cell Lung Cancer Diagnosed as Combined Small Cell Lung Cancer in a Surgical Specimen After Osimertinib Treatment

Background. The most common mechanism of resistance to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is the emergence of the T790M mutation. Osimertinib is initially effective after the appearance of this mutation, but the efficacy wanes over time. We report a case of EGFR mutation-positive non-small cell lung cancer that was pathologically diagnosed, based on the examination of a surgical specimen, as combined small cell lung cancer, which progressed during treatment with osimertinib. Case. A 46-year-old man presented with EGFR mutation-positive non-small cell lung cancer, with multiple brain metastases. Erlotinib treatment was initiated, and the primary lesion and brain metastases decreased in size. However, after 11 months, the primary lesion size increased and new brain metastases appeared. Re-biopsy revealed that the primary lesion was T790M-positive, and osimertinib therapy was initiated. Although the primary lesion increased, the other lesions were controlled, and the primary lesion was subsequently resected. The surgical specimen was subsequently diagnosed as combined small cell carcinoma, including adenocarcinoma and squamous cell carcinoma. Conclusion. We report a rare case in which a surgical specimen was diagnosed as combined small cell lung cancer following treatment with osimertinib. If the disease progressed during EGFR-TKI treatment, it was considered that the majority of the tumor histology might have changed. Aggressive re-biopsy was considered necessary to obtain a larger specimen.