Pulmonary Neuroendocrine Tumors Research Articles

Orthopedia homeobox protein (OTP) is a sensitive and specific marker for primary pulmonary carcinoid tumors in cytologic and surgical specimens

Orthopedia homeobox protein (OTP) was recently demonstrated to be a pulmonary neuroendocrine marker showing specificity for pulmonary carcinoid tumors in histologic sections. Little is known of OTP performance and specificity for pulmonary neuroendocrine tumors in lung fine-needle aspiration (FNA) cell blocks (CBs), however. We evaluated OTP expression in lung non-neuroendocrine and neuroendocrine tumor CBs to determine its diagnostic utility in these specimens. Pulmonary typical carcinoid (TC) and atypical carcinoid (AC), small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC), and squamous cell carcinoma (SQ) and adenocarcinoma (ADC) CBs were retrieved along with matched surgical cases and assessed for nuclear OTP expression with immunohistochemistry. Nuclear OTP was seen in 82% TCs (9 of 11) and 83% ACs (10 of 12), but not in SCLC (0 of 9), LCNEC (0 of 9), SQ (0 of 10) or ADC (0 of 6) cytology cases. Similar to the cytologic specimens, nuclear OTP was seen in 82% TCs (9 of 11) and 80% ACs (8 of 10) but in none of the SCLC (0 of 8), LCNEC (0 of 7), SQ (0 of 8) or ADC (0 of 6) resections. Both AC and TC CBs showed a similar percentage of cells expressing nuclear OTP. By contrast, in resection specimens, 30% ACs (3 of 10) compared with 73% TC (8 of 11) cases showed >40% of cells nuclear OTP staining. Nuclear OTP demonstrated 80-83% sensitivity and 100% specificity for pulmonary carcinoid tumors in cytology and surgical specimens. In the context of pulmonary malignancies, nuclear OTP immunohistochemistry is highly sensitive and specific in distinguishing carcinoid tumors from other pulmonary neuroendocrine and non-neuroendocrine malignancies in cytologic and surgical specimens.

Tumeurs neuro-endocrines broncho-pulmonaires primitives : tumeurs carcinoïdes, carcinomes neuro-endocrines à grandes cellules

Primary pulmonary neuroendocrine tumors comprise several distinct clinical entities, corresponding to four main subtypes : typical carcinoid tumors, of low grade malignancy ; atypical carcinoids of intermediate grade ; neuro-endocrine carcinomas with either small or large cells, which are high grade, frequent malignancy.The pre-treatment workup of carcinoid tumors is based on specific recommendations. Any clinical suspicion of an associated functional syndrome must be confirmed by the appropriate blood dosages.In case of metastatic carcinoid tumor, management relies on the control of a possible secretory syndrome by somatostatin analogues, in addition to the oncological treatment, based on the evaluation of tumor progression, with several opportunities : close follow-up, local treatment of metastases, treatment with somatostatin analogues, everolimus, or chemotherapy for tumor with high aggressiveness.In case of advanced, metastatic large-cell neuroendocrine carcinoma, molecular analysis of a panel of oncogenic alterations could guide the chemotherapy strategy ; platinum and etoposide combination has historically been used. In the second line, in the absence of any therapeutic standard, the IFCT-FFCD-GERCOR NIPINEC trial is opening in France in 2018 and aims at evaluating nivolumab, with or without ipilimumab in the second- and third-line setting.

Abstract IA28: The genomic landscape of SCLC and other neuroendocrine lung tumors

Abstract Small cell lung cancer (SCLC) accounts for 15% of all lung cancers and belongs to the family of pulmonary neuroendocrine tumors. This tumor subgroup additionally includes large-cell neuroendocrine carcinomas (LCNEC) and pulmonary carcinoids (PCA), which occur in 3% and 2% of all lung cancer patients, respectively. Carcinoids are usually clinically benign, whereas SCLC and LCNEC are characterized as high-grade malignant tumors. Clinical and histologic studies have suggested similarities between SCLC and LCNECs: Both lung tumor subtypes are associated with heavy smoking and reveal an aggressive tumor growth resulting in a poor overall survival. We have performed comprehensive and multilevel genomic profiling on SCLC and LCNECs, including genome, exome, and transcriptome sequencing. SCLC and LCNEC tumors reveal high mutation rates with an average of 9.5 and 8.6 mutations per megabase, respectively. Our sequencing studies have shown that SCLC tumors are characterized by bi-allelic inactivation of TP53 and RB1 in almost 100% of the cases. LCNECs, on the other hand, are composed of two mutually exclusive subgroups, which we categorized as “type I LCNECs” and “type II LCNECs.” Type I LCNECs harbor TP53 and STK11 or KEAP1 alterations. Despite sharing genomic alterations with lung adenocarcinomas and squamous cell carcinomas, type I LCNECs exhibit a high neuroendocrine profile with close similarity to SCLC tumors. Type II LCNECs harbor loss of TP53 and RB1, thus showing genetic resemblance to SCLC. However, these tumors were revealed to be different from the majority of SCLC with reduced levels of neuroendocrine markers, an upregulated immune signaling profile, and high activity of the NOTCH pathway. Conclusively, our studies show marked biologic differences between high-grade neuroendocrine lung tumors and we emphasize the precise distinction of LCNEC subgroups from SCLC. Citation Format: Julie George. The genomic landscape of SCLC and other neuroendocrine lung tumors [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr IA28.

Solitary Pulmonary Nodule

The solitary pulmonary nodule is a common finding that is observed in more than 150,000 persons each year in the United States. Factors influencing probability of malignancy are discussed, including age and environmental factors. Investigative studies are described. Imaging includes chest radiography, computed tomography, and positron emission tomography. Biopsy can be excisional or performed via transthoracic needle or bronchoscopy. The differential diagnosis is broad and can include malignant or benign lesions. Malignant lesions include nonsmall cell lung cancer, small cell lung cancer, pulmonary neuroendocrine tumors, and metastatic malignancies. Benign lesions can include pulmonary hamartoma or inflammatory or infectious nodules. Few, if any, randomized controlled trials exist to direct management. Most clinicians rely on a combination of single-institution studies, a few prospective trials, and clinical acumen to assess a given patient's risk profile to inform decisions on invasive and noninvasive testing. In this review, the tables describe the differential diagnosis of a solitary pulmonary nodule, factors affecting malignant probability of a solitary pulmonary nodule, and the initial assessment of probability of cancer in a solitary pulmonary nodule. This review contains 5 figures, 4 tables, and 73 references. Key Words: bronchoscopy, compute tomography, lung cancer, nodule, positron emission tomography, solitary

Prospective evaluation of 68 Ga-DOTATATE PET/CT in limited disease neuroendocrine tumours and/or elevated serum neuroendocrine biomarkers.

The 68 Ga-labelled somatostatin analogues (68 Ga-DOTA-SSAs) is becoming popular as an important diagnostic tool in neuroendocrine tumours as evidenced by a growing number of reports detailing institutional experience with various DOTA peptides. However, only few prospective studies have compared 68 Ga-DOTA-SSAs and somatostatin receptor scintigraphy (SRS) in gastroenteropancreatic neuroendocrine tumours (GEP-NETs) and pulmonary neuroendocrine tumours. The aim of our prospective study was to perform head-to-head comparison between 68 Ga-DOTATATE PET/CT and standard imaging work-up (SI) that included multiphasic CT, liver MRI and SRS using single photon emission computed tomography. In this prospective study, the patients were enrolled only if they met any of the following inclusion criteria: (i) initial staging of a NETs without distant metastases on SI or neuroendocrine tumour with unknown primary on SI; (ii) restaging of NETs that could be treated by focused therapeutic interventions; (iii) elevated serum neuroendocrine hormones or peptides. The exclusion criteria was grade 3 GEP-NETs. Thirty-two patients were enrolled in the study. Eleven patients (6 pancreas, 4 ileum, 1 duodenal) were included for initial evaluation and staging of NETs, 8 patients (5 pancreas, 1 ileal, 1 lung, 1 duodenal gastrinoma) for restaging, and 13 patients for elevated serum neuroendocrine biomarkers (5 ectopic Cushing's syndrome, 5 organic hypoglycaemia, 1 patient each with elevated vasoactive inhibitory peptide, chromogranin A and neuron-specific enolase). 68 Ga-DOTATATE PET/CT detected more primary tumours than SRS (15/18 vs 10/18: P=.074). The missed tumours on 68 Ga-DOTATATE PET/CT were located in the lung in two cases and duodenum in one case. For other anatomical regions (nodal and distant metastasis), no statistical difference was observed between imaging modalities using 68 Ga-DOTATATE PET/CT and SRS. Overall, 68 Ga-DOTATATE PET/CT+CT+MRI detected 31/33 of the involved regions (including primaries) (29 and 22 for 68 Ga-DOTATATE and SRS, respectively). Our study shows that 68 Ga-DOTATATE PET/CT detected similar number of sites than combination of SRS, liver MRI and thoraco-abdominopelvic CT on region-based analysis. 68 Ga-DOTATATE PET/CT missed half of primary lung carcinoids with ectopic Cushing's syndrome.

Quality of life in multiple endocrine neoplasia type 2A compared with normative and disease populations

BackgroundPatient-reported outcomes are measured in chronic disease states to inform intervention and management decisions while minimizing negative outcomes. We hypothesized that health-related quality of life in patients with multiple endocrine neoplasia type 2A would be worse than the general US population but similar to other chronic diseases. MethodsAdults ≥18 years with multiple endocrine neoplasia type 2A were recruited to complete the Patient-Reported Outcomes Measurement Information System 29-item questionnaire (n = 45). Scores based on the Patient-Reported Outcomes Measurement Information System T-score metric were compared with the general US population and with cohorts with low back pain, cancer, congestive heart failure, chronic obstructive pulmonary disease, major depressive disorder, rheumatoid arthritis, neuroendocrine tumors, primary hyperparathyroidism, and MEN1. ResultsCompared with US normative data, multiple endocrine neoplasia type 2A patients reported worse anxiety (58.2 ± 12.0, P < .0001), depression (55.4 ± 12.0, P < .01), fatigue (61.4 ± 10.8, P < .0001), pain interference (54.0 ± 11.5, P < .05), and sleep disturbance (56.9 ± 2.7, P < .001), as well as significantly lower physical functioning (45.7 ± 9.3, P < .01) and ability to participate in social roles (46.4 ± 9.7, P < .05). Multiple endocrine neoplasia type 2A patients reported greater fatigue than patients with cancer (P < .0001), chronic obstructive pulmonary disease (P = .01), rheumatoid arthritis (P = .0002), neuroendocrine tumors (P = .0007), and primary hyperparathyroidism (P < .0001) but higher physical functioning compared with patients with rheumatoid arthritis (P = .02), low back pain, congestive heart failure, and chronic obstructive pulmonary disease (P < .0001). ConclusionsThis study is the first to use the Patient-Reported Outcomes Measurement Information System to compare patient-reported outcomes between multiple endocrine neoplasia type 2A and other chronic conditions. Individuals with multiple endocrine neoplasia type 2A reported worse health-related quality of life in all 7 domains compared with US normative data. Multiple endocrine neoplasia type 2A patients reported greater fatigue but greater physical function compared with several other conditions. Prospective longitudinal evaluation of patient-reported outcomes in multiple endocrine neoplasia type 2A should be conducted to identify treatments associated with the highest health-related quality of life.

Treatment outcomes and incidence of brain metastases in pulmonary large cell neuroendocrine carcinoma

IntroductionLarge cell neuroendocrine carcinoma (LCNEC) is a rare type of high-grade pulmonary neuroendocrine tumor. The study objective is to investigate its survival outcomes, incidence of brain metastases, and patterns of recurrence. MethodsThis is a single center study of patients with pathologic diagnosis of pulmonary LCNEC. Patient data were collected retrospectively and analyzed, including survival, incidence of brain metastases, and patterns of recurrence. ResultsOf 87 patients (stages I: 24, II: 14, III: 23, IV: 26), 52 were managed curatively and 35 palliatively. The median follow-up time was 17.3 months (range 0.6-89.5) for those treated with curative intent and 7.0 months (range 0.1-28.6) for those treated palliatively. The 2- and 5-year overall survival (OS) rates are 48.4% and 25.5% for the curative group, with a median OS of 13.5 months. In the palliative group, the OS are 30.8% at 1 year and 6.8% at 2 years, with a median OS of 7.0 months. Thirty-eight of 52 (73%) patients treated with curative intent had disease relapse, with the common sites being regional lymph nodes (20), brain (18), bones (11), and liver (9). The incidence of brain recurrence among those managed curatively are 21.4% and 41.3%, respectively at 1 and 2 years. Of 18 patients experiencing brain metastases, 14 developed them as part of a first relapse. ConclusionsLCNEC's survival outcomes are poor. The incidence of brain metastases is higher than what is observed for other types of nonsmall cell lung cancers. Prophylactic cranial irradiation should be investigated as a means of improving outcomes.

Prognostic significance of PD-L1 expression and CD8+ T cell infiltration in pulmonary neuroendocrine tumors

BackgroundRecent research supports a significant role of immune checkpoint inhibitors in the treatment of solid tumors. However, relevant reports for programmed death-ligand 1 (PD-L1) and CD8+ tumor-infiltrating lymphocytes (TILs) in pulmonary neuroendocrine tumors (PNETs) have not been fully studied. Therefore, we investigated PNETs for the expression of PD-L1 and infiltration by CD8+ TILs as well as the prognostic value of both factors.MethodsIn total, 159 specimens of PNETs (35 TC, 2 AC, 28 LCNEC, 94 SCLC) were included in this study. Immunohistochemistry (IHC) was used to detect the expression of PD-L1 in these cases. Cases demonstrating ≥5% tumor cell expression or any expression (> 1%) of PD-L1 on immune cells were considered positive. CD8+ TILs both within stroma and tumor areas of invasive carcinoma were analyzed using whole-slide digital imaging. Manual regional annotation and machine cell counts were performed for each case.ResultsPositive expression of PD-L1 was observed in 72 cases (45.3%), including 9 cases (5.7%) with expression exclusively on tumor cells, 46 cases (28.9%) with expression exclusively on immune cells, and 17 cases (10.7%) with the expression on tumor cells and immune cells. PD-L1 expression was associated with necrosis (p < 0.001), high pathologic grade (p < 0.001) and histologic type (p < 0.001). No correlation was observed with overall survival (OS) (p = 0.158) or progression-free survival (PFS) (p = 0.315). In contrast, higher CD8+ T cell density was associated with the absence of vascular invasion (p = 0.004), histologic type (p = 0.005), negative lymph node metastasis (p = 0.005) and lower clinical staging (p = 0.007). Moreover, multivariate analysis revealed that CD8+ stromal TIL was an independent prognostic factor for improved OS (p = 0.009) and PFS (p = 0.002).ConclusionPD-L1 was expressed in approximately half of the PNETs. The majority of the expression was observed in immune cells. Positive expression of PD-L1 showed no correlation with OS or PFS, while higher CD8+ TILs within stroma was proved to be an independent prognostic factor for favorable OS and PFS of PNETs.

Predictors of Survival in 211 Patients with Stage IV Pulmonary and Gastroenteropancreatic MIBG-Positive Neuroendocrine Tumors Treated with 131I-MIBG.

This retrospective analysis identifies predictors of survival in a cohort of patients with meta-iodobenzylguanidine (MIBG)-positive stage IV pulmonary and gastroenteropancreatic neuroendocrine tumor (P/GEP-NET) treated with 131I-MIBG therapy, to inform treatment selection and posttreatment monitoring. Methods: Survival, symptoms, imaging, and biochemical response were extracted via chart review from 211 P/GEP-NET patients treated with 131I-MIBG between 1991 and 2014. For patients with CT follow-up (n = 125), imaging response was assessed by RECIST 1.1 if images were available (n = 76) or by chart review of the radiology report if images could not be reviewed (n = 49). Kaplan-Meier analysis and Cox multivariate regression estimated survival and progression-free survival benefits predicted by initial imaging, biochemical response, and symptomatic response. Results: All patients had stage IV disease at the time of treatment. Median survival was 29 mo from the time of treatment. Symptomatic response was seen in 71% of patients, with the median duration of symptomatic relief being 12 mo. Symptomatic response at the first follow-up predicted a survival benefit of 30 mo (P < 0.001). Biochemical response at the first clinical follow-up was seen in 34% of patients, with stability of laboratory values in 48%; response/stability versus progression extended survival by 40 mo (P < 0.03). Imaging response (20% of patients) or stability (60%) at the initial 3-mo follow-up imaging extended survival by 32 mo (P < 0.001). Additionally, multiple 131I-MIBG treatments were associated with 24 mo of additional survival (P < 0.05). Conclusion: Therapeutic 131I-MIBG for metastatic P/GEP-NETs appears to be an effective means of symptom palliation. Imaging, biochemical, and symptomatic follow-up help prognosticate expected survival after 131I-MIBG therapy. Multiple rounds of 131I-MIBG are associated with prolonged survival.

PKM1 Confers Metabolic Advantages and Promotes Cell-Autonomous Tumor Cell Growth

Expression of PKM2, which diverts glucose-derived carbon from catabolic to biosynthetic pathways, is a hallmark of cancer. However, PKM2 function in tumorigenesis remains controversial. Here, we show that,when expressed rather than PKM2, the PKM isoform PKM1 exhibits a tumor-promoting function in KRASG12D-induced or carcinogen-initiated mouse models or in some human cancers. Analysis of Pkm mutant mouse lines expressing specific PKM isoforms established that PKM1 boosts tumor growth cellintrinsically. PKM1 activated glucose catabolism and stimulated autophagy/mitophagy, favoring malignancy. Importantly, we observed that pulmonary neuroendocrine tumors (NETs), including small-cell lung cancer (SCLC), express PKM1, and that PKM1 expression is required for SCLC cell proliferation. Our findings provide a rationale for targeting PKM1 therapeutically in certain cancer subtypes, including pulmonary NETs.

Neuroendocrine Pulmonary Tumors of Low, Intermediate and High Grade: Anatomopathological Diagnosis-Prognostic and Predictive Factors.

Neuroendocrine tumors (NETs) belong to a heterogeneous family of rare tumors with very broad and complex clinical behavior. Due to their heterogeneity, the lack of specific symptoms and the absence of sensitive methods for early detection, patients are usually diagnosed when the disease is in an advanced state for which curative treatments are scarce. In most cases, these few treatments try to prolong the survival of patients, maintaining the quality of life. The identification of biomarkers could help to improve early diagnosis and to choose the most suitable therapeutic strategy. This paper provides a review of the current histopathological diagnostic approaches for lung NET subtypes, including the predictive and prognostic factors, to help in the early diagnosis of this disease.

Telomerase reverse transcriptase promoter region mutations and the clinical characteristics of pulmonary neuroendocrine tumors

Telomerase reverse transcriptase promoter region mutations and the clinical characteristics of pulmonary neuroendocrine tumors

Inflammation and PD-L1 expression in pulmonary neuroendocrine tumors.

In the light of novel cancer immune therapies, the status of antitumor inflammatory response and its regulation has gained much attention in patients with lung cancer. Ample datasets exist for non-small-cell lung cancer, but those for pulmonary neuroendocrine tumors are scarce and controversial. Here, tumor-associated inflammation, CD8+ cell infiltration and PD-L1 status were evaluated in a cohort of 57 resected carcinoids and 185 resected neuroendocrine carcinomas of the lung (58 large cell carcinomas and 127 small cell carcinomas). Data were correlated with clinicopathological factors and survival. Moderate or high tumor-associated inflammation was detected in 4 carcinoids (7%) and in 37 neuroendocrine carcinomas (20%). PD-L1 immunoreactivity was seen in immune cells of 73 (39%) neuroendocrine carcinomas, while tumor cells were labeled in 21 (11%) cases. Inflammatory cells and tumor cells in carcinoids lacked any PD-L1 expression. In neuroendocrine carcinomas, PD-L1 positivity in immune cells, but not in tumor cells, was associated with intratumoral CD8+ cell infiltration (P < 0.001), as well as with the severity of tumor-associated inflammation (P < 0.001). In neuroendocrine carcinomas, tumor-associated inflammation and PD-L1 positivity in immune cells correlated with prolonged survival and the latter factor was also an independent prognosticator (P < 0.01, hazard ratio 0.4 for overall survival, P < 0.001 hazard ratio 0.4 for disease-free survival). Taken together, in neuroendocrine tumors, antitumor inflammatory response and PD-L1 expression are largely restricted to neuroendocrine carcinomas, and in this tumor entity, PD-L1 expression in inflammatory cells is positively correlated to patient survival.

The use of Ki-67 labeling index to grade pulmonary well-differentiated neuroendocrine neoplasms: current best evidence

Although Ki-67 labeling index (Ki-67%) is not a diagnostic or grading criterion in the World Health Organization classification of pulmonary carcinoid tumor, oncologists often request this test. A survey was administered at a North American Society for Neuroendocrine Tumors meeting to understand how Ki-67% is used in oncologic practices. A systematic literature review was performed to gather best evidence regarding the use of Ki-67%. Consecutive pulmonary carcinoids were stratified into pulmonary typical carcinoids with Ki-67% <5% (group A, n = 187), typical carcinoids with Ki-67% ≥5% (group B, n = 38) and atypical carcinoids irrespective of Ki-67% (group C, n = 31). Overall survival, progression-free survival, recurrence proportions and time to recurrence were compared, by group, using the log-rank test, chi-square statistics and ANOVA, respectively. Our survey confirmed that Ki-67% is frequently used by specialists caring for these patients. Ki-67% of 1–7% significantly correlated with overall survival in the literature but we found no information about Ki-67% cut-off values that would accurately distinguish pulmonary typical from atypical carcinoids or estimate the prognosis of patients stratified by World Health Organization diagnosis and Ki-67% cut-off. Overall survival was significantly different in our 3 patient groups (p < 0.001), with survival probabilities decreasing from groups A to C. Progression-free survival was significantly longer in group A than B (p < 0.007). Our results support the concept that by combining World Health Organization diagnosis and Ki-67%, pulmonary carcinoids can be stratified into 3 grades: G1 (typical carcinoids with Ki-67% <5), G2 (typical carcinoids with Ki-67% ≥5%) and G3 (atypical carcinoids) with different prognoses.

Processing Escape Mechanisms Through Altered Proteasomal Cleavage of Epitopes Affect Immune Response in Pulmonary Neuroendocrine Tumors

Background:Immunotherapy, especially immune checkpoint inhibition, is one of the most sophisticated approaches in cancer therapy. Immune checkpoint inhibition has already been successfully applied for treatment of non-small cell lung cancer and various other entities. Unfortunately, 60% of the cases show signs of therapy resistance. Additionally, a proportion of cases shows initial insensitivity to immune checkpoint inhibition. We consider a novel escape mechanism in association with deficient proteasomal epitope processing to be one prominent reason for initial insensitivity and therapy resistance. Therefore, we aim to identify mutations in association with these so-called processing escapes, in a highly diverse collective of pulmonary neuroendocrine lung tumors.Materials and Methods:Seventy representative tumor specimens of pulmonary neuroendocrine lung tumors were analyzed retrospectively via immunohistochemical detection of CD4, CD8, CD68, and CD20 as well as programmed cell death protein 1 and programmed cell death 1 ligand 1 for tumor immune infiltration and composition. Afterward, samples were screened for alterations in 48 genes, including 221 known mutational hotspots by massive parallel sequencing using the Illumina TruSeq Amplicon-Cancer Panel. For prediction of proteasomal cleavage probabilities, an R implementation of the machine learning tool NetChop 3.1 was utilized.Results:Immune cell infiltration of different compositions could be found in the majority of tumors. Deficient epitope processing was revealed to be a common event in those with steady distribution across all different subtypes. Despite immune infiltration, no significant antitumor response could be detected.Conclusion:Since it is widely acknowledged that tumors need to avoid the immune system to ensure their survival, processing escapes should already be present during primary tumor development. In line, processing escapes can be found in all tumors, regardless of subtype and mutational burden. Furthermore, there is solid evidence that processing escapes have a negative impact on the antitumor activity of tumor infiltrating immune cells.

Cyclical Cushing syndrome due to pulmonary neuroendocrine tumor: a case report

Cyclical Cushing syndrome due to pulmonary neuroendocrine tumor: a case report

Resection concepts for early stage neuroendocrine tumors of the lungs and bronchi

Neuroendocrine tumors of the lungs are avery inhomogeneous group of malignancies. The surgical treatment should be adapted to the anatomical localization and histological subtype and individualized according to the functional reserve. We performed aselective review of current literature, which was supplemented by personal experiences. The currently available outcome data are very inhomogeneous and depend on the histological subtype of neuroendocrine pulmonary tumors. Aradical R0 resection is the key for an improvement in long-term overall and disease-free survival. Surgical treatment of carcinoid tumors is the current standard therapy. Sleeve resection should be performed, whenever possible. More aggressive tumors, such as large cell neuroendocrine carcinoma and small cell lung cancer should be treated in amultimodal concept.

Surgical options in the treatment of endobronchial carcinoid tumor

Abstract Endobronchial carcinoid tumors (ECT) are the most common pulmonary neuroendocrine tumor in the pediatric population. We report two cases of ECT in children who presented with recurrent pneumonia and bronchial asthma-like symptoms. Rigid bronchoscopy revealed an endobronchial mass with biopsy confirming the diagnosis. Both children underwent surgical resection with an uneventful post-operative course. Neither of children required adjuvant chemotherapy nor radiotherapy and with a mean of follow-up of 8 years with no recurrence. Physicians should be aware that children with recurrent pneumonia and asthma-like symptoms may have ECT. Appropriate investigations including CT scan, bronchoscopy, and biopsy would ensure early diagnosis and surgery.

Nationwide multicenter study on the management of pulmonary neuroendocrine (carcinoid) tumors.

Background and aimTo analyze the management and outcome of patients with primary typical (TC) and atypical lung carcinoids (AC) in Switzerland.MethodsRetrospective analysis of patients selected from a neuroendocrine tumor (NET) registry. Patients were divided into TC and AC according to pathology reports, and surgical procedures were grouped as wedge/segmentectomy, lobectomy/bilobectomy and pneumectomy. Survival analysis was performed using the Kaplan–Meier method and log-rank test.ResultsOver 7 years, 113 pulmonary carcinoids (61.9% females, mean age 59.4 years) were included from 19 hospitals, with pathology data on Ki67 and necrosis incomplete in 16 cases. Eighty-three TC and 14 AC underwent surgical resection with a primary tumor size of median 14.5 (range 1–80) mm and diagnosis was established in 55.8% at surgery. Mean follow-up was 30.2 ± 23.1 months. Lobectomy was performed in 54.2% and wedge resection in 17.7% of cases. Six patients received additional systemic therapy. There was a trend for larger primary lesion size and a significantly higher rate of N2–N3 status in AC. Mean survival tended to be increased in patients with TC compared to AC (86.1 vs 48.4 months, P = 0.06) and mean disease-free interval after surgical resection was 74.1 and 48.3 months for TC and AC, respectively (P = 0.74).ConclusionAC of the lung has a more malignant behavior and a trend to a worse outcome. The results of this registry reinforce the need for standardized histological diagnosis and inter-disciplinary therapeutic decision making to improve the quality of care of patients with TC and AC.

MTE 17.02 Surgical Strategy for the Treatment of Neuroendocrine Tumors

Neuroendocrine tumors (NETs) are a distinct subgroup of neoplasms arising from the neuroendocrine cells. Due to the peculiar morphological, immunohistochemical and molecular characteristics, NETs are usually classified as a separate group of tumors among solid malignancies. Thoracic NETs include the pulmonary and the thymic NET. Pulmonary NETs (PNETs) comprise well-differentiated neuroendocrine tumors (typical carcinoid), moderately-differentiated neuroendocrine tumors (atypical carcinoid), the latter two grouped as Bronchial Carcinoids (BCs); large cell neuroendocrine carcinoma (LCNEC) and small-cell lung carcinoma (SCLC).