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A 70-year-old woman underwent right upper lobectomy for adenocarcinoma of the lung (pT1bN2M0 stage IIIA). Five years after the surgery, lymph node recurrence was detected. Gefitinib was administered because epidermal growth factor (EGFR) exon 19 deletion mutation was detected in the previously resected surgical specimen. After a treatment of first-generation EGFR tyrosine kinase inhibitors, an FDG-PET/CT scan demonstrated abnormal FDG uptake in the pleura indicating pleural dissemination. Pleurocentesis revealed tumor cells in the pleural fluid; however, EGFR mutation testing failed due to inadequate tumor cellularity. Thoracoscopy under local anesthesia revealed multiple nodules on the parietal pleura. A biopsy specimen confirmed the diagnosis of lung adenocarcinoma with pleural dissemination and revealed EGFR exon 20-T790M mutation.

A 65-year-old woman visited our hospital due to right chest pain and dyspnea on exertion. Chest radiography revealed decreased permeability of the right lung. Computed tomography demonstrated a huge mass in the right upper lobe and right pleural effusion. Right pleural effusion cytology yielded a diagnosis of adenocarcinoma and was positive for mutation of epidermal growth factor receptor (EGFR; exon 21 L858R). Afatinib was selected for the initial treatment. Multiple tumors regressed remarkably, but then rapidly progressed 3 months later. We performed re-biopsy to detect the mechanism of resistance to afatinib. Histopathology revealed a mixture of small cell carcinoma (SCC) and adenocarcinoma harboring same EGFR mutation. To the best of our knowledge, this is the first report of transformation to SCC after treatment with afatinib.

A 73-year-old man was referred to our hospital after a 2-week history of bloody sputum and cough. Computed tomography (CT) images of the chest showed a mass grouped with mediastinal lymph nodes, and bronchoscopy showed a projecting mass in the right main bronchus. After a transbronchial biopsy, the patient was diagnosed with squamous cell carcinoma (T4N2M0 stage IIIB). The patient was treated with systemic chemotherapy, consisting of cisplatin (40 mg/m2, days 1 and 8) and docetaxel (30 mg/m2, days 1 and 8), and concurrent thoracic irradiation at a daily dose of 2 Gy. On day 35 of treatment, the patient complained of a sore throat and cough. A CT of the chest showed punctate low-attenuation foci between the esophagus and bronchus. Gastrointestinal endoscopy and bronchoscopy demonstrated a fistula in the middle intrathoracic esophagus and the left main bronchus. The patient’s symptoms gradually improved, and the fistula was closed after the suspension of chemoradiotherapy. Radiotherapy was resumed and completed on day 82. However, on day 108, he developed a fever and cough, and a tumor with fistula was revealed in the right main bronchus. He had an esophageal stent inserted, but he later died of sudden hemoptysis.