Pulmonary Large-Cell Neuroendocrine Carcinoma

Lung neuroendocrine tumors are a heterogeneous sub-type of pulmonary cancers representing approximately 20% of all lung cancers, including small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC). The frequency appears to be approximately 3% for LCNEC. Diagnosis of LCNEC requires attention to neuroendocrine features by light microscopy and confirmation by immunohistochemical staining for neuroendocrine markers. Both SCLC and pulmonary LCNEC are high-grade and poor-prognosis tumors, with higher incidence in males and smokers and peripheral localization. LCNEC is very rare, and the precise diagnosis on small specimens is very difficult, so we have still too few data to define a standard of treatment for pulmonary LCNECs. Data of literature, most based on retrospective analysis, indicated a poor 5-year overall survival, with a high incidence of recurrence after surgery, even in stage I disease. Primary surgery should be the first option in all operable patients because there is no validate therapeutic approach for LCNEC due to lack of clinical trials in this setting. Neoadjuvant platinum based regimens remain only an option for potentially resect-able tumors. In advanced stages, SCLC-like chemotherapy seems the best option of treatment, with a good response rate but a poor overall survival (from 8 to 16 months in different case series). New agents are under clinical investigation to improve LCNEC patients' outcome. We reviewed all data on treatment options feasible for pulmonary LCNEC, both for localized and extensive disease. L ung neuroendocrine tumors are a heterogeneous group of cancers originating from neuroendocrine cells in the pulmonary and bronchial epithelium and represent 20% of all lung cancers. 1 In the 1970s, pulmonary neuroendocrine tumors were classified into three histologically defined categories: typical carcinoids (TC), atypical carcinoids (AC), usually defined as carcinoids, and the more undifferentiated entity represented by small-cell lung cancer (SCLC). 2 In 1991, Travis et al. introduced a new distinct category of lung cancer, defined as large-cell neuroendocrine carcinoma (LCNEC), which showed large cells with abundant cytoplasm, necrotic areas, a high mitotic rate, and neuroendocrine features. It shared some characteristics with SCLC, while differing because this latter presents smaller cells, with low nuclear/cytoplasm ratio and a different pattern of tissue invasiveness. Organization recognizes LCNEC as a variant of large cell carci-noma (LCC), a type of non–small-cell lung cancer (NSCLC) and one of the four major types of lung neuroendocrine tumors. 4–6 Currently, LCNECs are considered as a separate entity for clinical characteristics, histology, prognosis, and survival. Pulmonary …