J Int Med Res. 2020 Jun; 48(6): doi: 10.1177/0300060520927918

A 52- year -old male nonsmoker visited our hospital because of an abnormal chest X-ray finding during routine screening. Chest computed tomography (CT) showed a mass in the right lower lung lobe. He underwent right lower lobectomy with regional lymph node dissection on December 11, 2014. The pathological diagnosis was invasive ADC with metastasis to lymph nodes in group 7 (1/1), group 9 (0/1), group 10 (0/5), and group 11 (0/1) on December 17, 2014 (Figure 1). Carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and progastrin-releasing peptide (ProGRP) were monitored after surgery on January 6, 2015 (Table 1). EGFR analysis revealed exon 19 deletion mutation. We carried out immunohistochemical examination of the lobectomy specimen and found that RB1 and TP53 were inactivated. The patient was diagnosed with T1bN2M0, stage IIIA, and received four cycles of chemotherapy combined with antiangiogenic therapy, consisting of vinorelbine, cisplatin, and endostar. Ten months later, after completing the 4th cycle, a CT scan revealed a lesion on the bronchial stump and new mediastinal lymph node metastases. CEA, NSE and ProGRP was monitored on January 12, 2016 (Table 1). The patient started treatment with erlotinib 150 mg orally once daily on January 18, 2016 and achieved a partial response within 1 month. Regular CT examinations were conducted every 2 months. However, after 1 year of erlotinib treatment, the primary lung tumor had regrown and the patient had symptoms of cough and shortness of breath. Transbronchial biopsy of a pulmonary metastatic nodule was performed to determine the pathological type and EGFR mutation status. Histopathologic examination of the biopsy sample indicated high-grade ADC on February 17, 2017 (Figure 2). We also carried out immunohistochemical examination of the metastatic nodule and found that RB1 and TP53 were inactivated. DNA extracted from the lung biopsy sample (see below) showed EGFR T790M and exon 19 deletion. The patient was prescribed osimertinib, and his cancer remained well-controlled for 15 months.

However, a CT scan then showed disease progression, and histologic analysis of a repeat transbronchial lung biopsy showed SCLC on June 23, 2018 (Figure 3). CEA, NSE and ProGRP was monitored on June 28, 2018 (Table 1). Next-generation sequencing (NGS) of peripheral blood revealed EGFR exon 19 deletion, T790M mutation, cis-C797S mutation, and a loss of RB1. Based on the transformation from NSCLC to SCLC, the patient was treated with six cycles of etoposide and cisplatin therapy. CT examination after the second and fourth cycles showed reduced pulmonary lesions, but no partial response. The patient’s disease progressed quickly after the sixth cycle, and he was administered two cycles of paclitaxel plus cisplatin chemotherapy. CT examination then showed partial response. The patient received further treatment and was followed-up.