Adenocarcinoma Of Lung Accompanied EGFR Gene Mutation Transformed Into Large Cell Neuroendocrine Cancer—Case Report And Review Of The Literature

[Background and objective]In most countries of the world, lung cancer remains one of the leading causes of cancer-related morbidity and mortality. The incidence of non-small cell lung cancer (NSCLC) accounts for about 85% of all of lung cancers, and NSCLC is composed of adenocarcinoma, squamous cell carcinoma and large cell cancer. The 2016 NCCN guideline suggested that the first-line therapy of adenocarcinoma accompanied EGFR wild-type mutated gene is targeted treatment of EGFR-TKI, which including erlotinib, gefitinib, and icotinib. Large cell neuroendocrine carcinoma (LCNEC) of lung is an important composition of non-small cell carcinoma. LCNEC also belongs to neuroendocrine tumors which including typical carcinoid, atypical carcinoid, and small cell carcinoma. LCNEC is a rare tumor and account of about 1.6-3.1% among all lung cancers. Since the poor incidence, LCNEC is often mistake as adenocarcinoma of lung and the primary treatment is usually disappointing. We reported a case in which adenocarcinoma was transformed into LCNEC, and searched large quantity of documents to considered the mechanism of adenocarcinoma transformed into LCNEC.[Methods]Here we share a case that adenocarcinoma of lung with EGFR mutation of exon 19 and 21 accompanied intracranial metastasis. After 3 cycles of PP chemotherapy, the disease was progressed. Then, we used erlotinib and brain tumor radiation, and again got a progressed disease. Afterwards, we conducted a puncture biopsy of lung, The pathological diagnosis showed as large call neuroendocrine cancer accompanied with adenocarcinoma composition. According to this diagnosis, we stopped the administration of erlotinib and use another chemotherapy regimen consisted of cisplatin and etoposide. We reviewed related literature to discuss the disease of LCNEC and the relationship of EGFR mutation and targeted therapy in LCNEC.[Conclusions]According to treatment experiment from this patient and reviewed large quantity of articles, large cell neuroendocrine carcinoma (LCNEC) of lung is highly invasive and progress rapidly. After adenocarcinoma transformed into SCLC, low expression of EGFR and Rbl was observed. The same phenomenon was also observed in a case of adenocarcinoma transformed into LCNEC patient. Considering similarities between SCLC and LCNEC of clinical features, response rate to chemotherapy, common pathway maybe exist between adenocarcinoma transformed into SCLC and LCNEC. However, more retrospective and prospective experiment still needs to be down to draw a conclusion.