Circulating Cell-Free DNA in Neuroendocrine Lung Tumors: Preliminary Data from a Prospective Surgical Series

P1.07-051 Incidence and Clinical Characteristics of Pulmonary Large-Cell Neuroendocrine Carcinoma: An Overview of Our Own Data

Neuroendocrine lung neoplasms are a heterogeneous group of tumors with different clinical behavior and prognosis. To evaluate the expression of p53, KLF4, and p21 in neuroendocrine lung neoplasms and to analyze the influence that expression has on the prognosis of those tumors. All neuroendocrine lung neoplasms (N = 109) resected in our institution were reviewed, with the collection of histologic slides and paraffin blocks of 47 typical carcinoids (43%), 9 atypical carcinoids (8%), 35 large cell neuroendocrine carcinomas (32%), and 18 small cell lung carcinomas (17%), as well as 10 tumorlets (100%). Four tissue microarrays were performed. Follow-up was assessed in all cases (119 of 119; 100%). p53 protein immunostaining results were negative in both the tumorlets and typical carcinoids and were overexpressed in 11% (1 of 9) of the atypical carcinoids and in 68% (36 of 53) of the carcinomas. KLF4 results were positive in all tumorlets (10 of 10; 100%), 32% (15 of 47) of the typical carcinoids, 44% (4 of 9) of the atypical carcinoids, and 62% (33 of 53) of the carcinomas. p21 expression did not differ among the groups. The lack of KLF4 and p21 expression was associated with an accumulation of aggressive features in typical carcinoids (P = .04 and P = .004, respectively, Fisher exact test). p53, KLF4, and p21 showed altered expression patterns in pulmonary neuroendocrine neoplasms. Lack of KLF4 and p21 expression was associated with accumulation of aggressive features in typical carcinoids.

Independent value of fascin immunoreactivity for predicting lymph node metastases in typical and atypical pulmonary carcinoids

Molecular biology of neuroendocrine lung tumors

Different micro-RNA expression profiles distinguish subtypes of neuroendocrine tumors of the lung: results of a profiling study

ED04.01 Surgery in Bronchopulmonary Typical and Atypical Carcinoids

Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids.

Knowledge of Pulmonary Neuroendocrine Tumors: Where Are We Now?

Lung cancer is leading cause of cancer death in many advanced countries and one of the challenging malignancies because of poor prognosis. Lung cancer is traditionally divided into two major categories, so called small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) because of distinctive prognostic and treatment strategies between them. On the other hand, there is a spectrum of tumors called pulmonary neuroendocrine (NE) tumors that are thought to originate from neuroendocrine cells in the pulmonary and bronchial epithelium. Until recently, pulmonary NE tumors were classified into three categories, i.e., typical carcinoid (TC), atypical carcinoid (AC), and SCLC. Large cell neuroendocrine carcinoma (LCNEC) of the lung was officially identified by Travis et al. in 1991 as a fourth category, a unique higher grade NSCLC existing between TC and SCLC (Travis et al., 1991). It is often difficult to diagnose LCNEC with small biopsy specimens because accurate diagnosis needs morphological and immunohistochemical information. Although earlier reports mainly focused on prognosis after surgical procedures, several recent studies reported on the efficacy of chemotherapy for advanced LCNEC. Because of the limited numbers of cases (in surgical series, LCNEC represents ~3% of lung cancers), large scale prospective studies have not been reported. Standard treatment for LCNEC, especially if advanced, is not established although LCNEC is included in NSCLC in the treatment algorithm in many guidelines. However, accumulating data including recent retrospective studies have suggested that there is similarity in the prognosis and treatment response between LCNEC and SCLC. In this review, we will focus on the treatment of advanced LCNEC for the better selection of chemotherapeutic regimens for the patients with this relatively rare lung cancer.

Pulmonary neuroendocrine tumors: Incidence and prognosis of histological subtypes. A population-based study in Denmark

Molecular and cellular biology of neuroendocrine lung tumors: Evidence for separate biological entities

Prognostic factors in neuroendocrine lung tumors: a Spanish multicenter study

MTP22-01: Neuroendocrine tumors

Neuroendocrine tumors may develop throughout the human body with the majority being found in the gastrointestinal tract and bronchopulmonary system. Neuroendocrine tumors are classified according to the grade of biological aggressiveness (G1–G3) and the extent of differentiation (well-differentiated/poorly-differentiated). The well-differentiated neoplasms comprise typical (G1) and atypical (G2) carcinoids. Large cell neuroendocrine carcinomas as well as small cell carcinomas (G3) are poorly-differentiated. The identification and differentiation of atypical from typical carcinoids or large cell neuroendocrine carcinomas and small cell carcinomas is essential for treatment options and prognosis. Pulmonary neuroendocrine tumors are characterized according to the proportion of necrosis, the mitotic activity, palisading, rosette-like structure, trabecular pattern and organoid nesting. The given information about the histopathological assessment, classification, prognosis, genetic aberration as well as treatment options of pulmonary neuroendocrine tumors are based on own experiences and reviewing the current literature available. Most disagreements among the classification of neuroendocrine tumor entities exist in the identification of typical versus atypical carcinoids, atypical versus large cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas versus small cell carcinomas. Additionally, the classification is restricted in terms of limited specificity of immunohistochemical markers and possible artifacts in small biopsies which can be compressed in cytological specimens. Until now, pulmonary neuroendocrine tumors have been increasing in incidence. As compared to NSCLCs, only little research has been done with respect to new molecular targets as well as improving the classification and differential diagnosis of neuroendocrine tumors of the lung.

e19120 Background: The incidence and prevalence of Neuroendocrine Neoplasms (NENs) are rapidly rising. Epidemiologic trends have been reported for common NENs, but specific data for lung NENs has been lacking. Methods: We conducted a retrospective population-based analysis utilizing the Surveillance, Epidemiology, and End Results (SEER) database, and studied lung NENs patients from 1988 to 2015. Associated population data was utilized to report the annual age-adjusted incidence and overall survival trends. Trends in the incidence and survival of large-cell lung cancer (LCLC) and atypical carcinoid (AC) were reported from 2000-2015, while that for typical carcinoid (TC) and small cell lung cancer (SCLC) were reported from 1988-2015. Results: We examined a total of 115,995 lung NENs [103,980 – SCLC; 3,303 – LCLC; 8,146 – TC; 656 – AC]. The age-adjusted incidence rate revealed decline in SCLC from 8.6 in 1988 to 5.3 in 2015 per 100,000; while other NENs showed an increase: TC increased from 0.57 in 1988 to 0.77 in 2015 per 100,000, AC increased from 0.17 in 2001 to 0.22 in 2015 per 100,000, and lastly, LCLC increased from 0.35 in 2001 to 0.41 in 2015 per 100,000. On multivariable analyses, the median overall survival (OS) and disease-specific survival (DSS) rate varied significantly by stage, grade, age at diagnosis, histological type, insurance type, marital status, and race. The 5-year OS rate among SCLC and LCLC patients was 5% and 17%, respectively, consistent with their high-grade nature. On the other hand, TC and AC, representing low-grade neuroendocrine tumors, had good 5-year OS: 84% and 64%, respectively. Conclusions: The incidence of lung NENs is rising, possibly because of advanced radiological techniques. However, we have seen a downtrend in the incidence of SCLCs likely because of declining smoking habits. Such population-based studies are essential for resource allocation and to prioritize future research directions.