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      Lung Large Cell Neuroendocrine Carcinoma: An Analysis of Patients from the Surveillance, Epidemiology, and End-Results (SEER) Database

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          Abstract

          Background

          The aim of this study was to assess the incidence, clinicopathologic characteristics, prognostic factors, and treatment outcomes in lung large cell neuroendocrine carcinoma (LCNEC).

          Material/Methods

          Patients diagnosed with lung LCNEC between 2000 and 2013 were identified using the Surveillance, Epidemiology, and End-Results database. Kaplan–Meier methods and univariate and multivariate analyses were used for statistical analysis.

          Results

          A total of 2097 patients were identified. The total age-adjusted incidence rate of lung LCNEC was 0.3/100 000, with a rise in incidence over the study period. The 5-year lung cancer-specific survival (LCSS) and overall survival (OS) were 20.7% and 16.7%, respectively. Multivariate analysis indicated that age ≥65 years, male sex, advanced tumor stage, advanced nodal stage, not undergoing surgery. and not undergoing chemotherapy were independent adverse indicators for survival outcomes. After stratification by tumor stage, undergoing surgery was associated with more favorable LCSS and OS compared with those without surgery, regardless of tumor stage.

          Conclusions

          LCNEC is a rare lung cancer subtype with a dismal prognosis. Primary surgical treatment has significant survival benefits, even for stage IV patients. The optimal treatment strategies for lung LCNEC require further investigation.

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          Most cited references31

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          Pulmonary Large-Cell Neuroendocrine Carcinoma

          Lung neuroendocrine tumors are a heterogeneous subtype 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 resectable 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.
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            Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma. An ultrastructural, immunohistochemical, and flow cytometric study of 35 cases.

            Based on our review of 35 cases and the literature, we found the spectrum of pulmonary neuroendocrine (NE) tumors to be too broad to fit into the traditional three-category classification scheme of typical carcinoid (TC), atypical carcinoid (AC), and small-cell lung carcinoma (SCLC). We found that a spectrum of high- and low-grade tumors exist between TC and SCLC and that in the past many of these tumors have been called AC. We chose to adhere to Arrigoni's definition of AC, as his original criteria characterized a low-grade tumor. For the higher grade non-small-cell tumors (NSCLC), we propose a fourth category of large-cell neuroendocrine carcinoma (LCNEC), which is characterized by: (a) light microscopic NE appearance; (b) cells of large size, polygonal shape, low nuclear-cytoplasmic ratio (N:C), coarse nuclear chromatin, and frequent nucleoli; (c) high mitotic rate [greater than 10/10 high-power fields (HPF)] and frequent necrosis; and (d) NE features by immunohistochemistry (IHC) or electron microscopy (EM). Thus, after deciding that a pulmonary NE tumor is high grade, the major diagnostic issue is separation of LCNEC from SCLC. This distinction is based not only on cell size, but on a variety of morphologic features. We studied 20 TC, six AC, five LCNEC, and four SCLC and characterized the clinical, light microscopic, EM, IHC, and flow cytometric features of each type of tumor. We did not find any advantage to IHC, EM, or flow cytometry over light microscopy in the subclassification or prediction of prognosis; however, these methods were useful in characterizing these four types of pulmonary NE tumors and in demonstrating their NE properties. LCNEC must be distinguished from a fifth category pulmonary NE tumor: NSCLC with NE features in which NE differentiation is not evident by light microscopy and must be demonstrated by EM or IHC. Although the prognosis of LCNEC appears to be intermediate between AC and SCLC, larger numbers of patients will be needed to demonstrate significant differences in survival.
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              Large Cell Neuroendocrine Carcinoma of the Lung: Clinico-Pathologic Features, Treatment, and Outcomes.

              Large cell neuroendocrine carcinoma (LCNEC) accounts for approximately 3% of lung cancers. Pathologic classification and optimal therapies are debated. We report the clinicopathologic features, treatment and survival of a series of patients with stage IV LCNEC.
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                Author and article information

                Journal
                Med Sci Monit
                Med. Sci. Monit
                Medical Science Monitor
                Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
                International Scientific Literature, Inc.
                1234-1010
                1643-3750
                2019
                16 May 2019
                : 25
                : 3636-3646
                Affiliations
                [1 ]Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Institute of Radiotherapy and Oncology, Soochow University, Suzhou, Jiangsu, P.R. China
                [2 ]Department of Radiation Oncology, Cancer Hospital, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, Fujian, P.R. China
                Author notes
                Corresponding Authors: San-Gang Wu, e-mail: unowu12345@ 123456hotmail.com , Ye Tian, e-mail: dryetian@ 123456126.com
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                Article
                914541
                10.12659/MSM.914541
                6537662
                31095532
                91e2ea13-aa8b-457c-a1ff-2d8eb2ed6c6a
                © Med Sci Monit, 2019

                This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International ( CC BY-NC-ND 4.0)

                History
                : 10 December 2018
                : 29 January 2019
                Categories
                Clinical Research

                carcinoma, non-small-cell lung,epidemiologic study characteristics as topic,survival analysis

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