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https://www.readbyqxmd.com/read/29656752/large-cell-neuroendocrine-lung-carcinoma-induces-peripheral-t-cell-repertoire-alterations-with-predictive-and-prognostic-significance
#1
Petros Christopoulos, Marc A Schneider, Farastuk Bozorgmehr, Jonas Kuon, Walburga Engel-Riedel, Jens Kollmeier, Volker Baum, Thomas Muley, Philipp A Schnabel, Helge Bischoff, Christian Grohé, Monika Serke, Michael Thomas, Paul Fisch, Michael Meister
OBJECTIVES: This study was performed to evaluate for a potentially important role of T cells in the pathophysiology and treatment sensitivity of large cell neuroendocrine lung carcinoma (LCNEC), an orphan disease with poor prognosis and scarce data to guide novel therapeutic strategies. MATERIALS AND METHODS: We performed T-cell receptor (TCR) β-chain spectratyping on blood samples of patients treated within the CRAD001KDE37 trial (n = 35) using age-matched current or former (n = 11) and never smokers (n = 10) as controls...
May 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29581877/immune-checkpoint-inhibitors-in-large-cell-neuroendocrine-carcinoma-current-status
#2
Aman Chauhan, Susanne M Arnold, Jill Kolesar, Hala Elnakat Thomas, Mark Evers, Lowell Anthony
Introduction: Large cell neuroendocrine carcinomas (LCNEC) are a group of rare high grade neuroendocrine tumors that often behave clinically like small cell carcinoma (SCLC) and are treated as such. No major advancement in the management of these tumors has occurred in the last 30 years. Methods: We present a case series of three cases from Markey Cancer center along with a review of 13 published cases in the literature wherein immune-checkpoint inhibitors were utilized in the management of LCNEC...
March 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29572007/pd-l1-expression-in-large-cell-neuroendocrine-carcinoma-of-the-lung
#3
F Eichhorn, A Harms, A Warth, T Muley, H Winter, M E Eichhorn
OBJECTIVES: Large cell neuroendocrine carcinoma of the lung (LCNEC) is associated with an unfavorable prognosis and only few patients are eligible for surgery. In most patients, chemotherapy is recommended alone or in addition to resection. Novel immunotherapies blocking the PD-L1 pathway have been introduced into therapeutic regimens for NSCLC with great success. In order to evaluate a possible efficacy of an anti-PD-L1 therapy, we analyzed the frequency of PD-L1 expression in LCNEC...
April 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29564132/large-cell-neuroendocrine-carcinoma-arising-in-the-endometrium-a-case-report
#4
Jumpei Ogura, Yasushi Adachi, Koji Yasumoto, Akiharu Okamura, Hirofumi Nonogaki, Kazuyo Kakui, Koji Yamanoi, Koh Suginami, Takashi Koyama, Susumu Ikehara
Large-cell neuroendocrine carcinoma (LCNEC) of the endometrium is an extremely rare, high-grade malignant tumor. We herein report a case of a rapidly growing LCNEC arising in the endometrium. A 52-year-old woman was referred to Toyooka Hospital (Tooyoka, Japan) due to genital bleeding in February 2016. There had been no abnormalities on a regular gynecological and physical examination 3 months prior to the consultation. Imaging (computed tomography and magnetic resonance imaging) and a pelvic examination revealed a tumor sized 16...
April 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29556964/human-papillomavirus-related-neuroendocrine-carcinomas-of-the-head-and-neck
#5
William H Westra
Human papillomavirus (HPV)-related head and neck carcinoma (HNC) represents an important subgroup of head and neck cancer that is characterized by a consistent microscopic appearance and a favorable prognosis. A growing experience with HPV testing, however, has uncovered variants that deviate from the prototypic HPV-HNC with respect to morphology. While these HPV-HNCs may deviate morphologically from the prototype, they do not appear to stray far from the favorable clinical outcome assigned to HPV-positive status...
March 20, 2018: Head and Neck Pathology
https://www.readbyqxmd.com/read/29535388/integrative-genomic-profiling-of-large-cell-neuroendocrine-carcinomas-reveals-distinct-subtypes-of-high-grade-neuroendocrine-lung-tumors
#6
Julie George, Vonn Walter, Martin Peifer, Ludmil B Alexandrov, Danila Seidel, Frauke Leenders, Lukas Maas, Christian Müller, Ilona Dahmen, Tiffany M Delhomme, Maude Ardin, Noemie Leblay, Graham Byrnes, Ruping Sun, Aurélien De Reynies, Anne McLeer-Florin, Graziella Bosco, Florian Malchers, Roopika Menon, Janine Altmüller, Christian Becker, Peter Nürnberg, Viktor Achter, Ulrich Lang, Peter M Schneider, Magdalena Bogus, Matthew G Soloway, Matthew D Wilkerson, Yupeng Cun, James D McKay, Denis Moro-Sibilot, Christian G Brambilla, Sylvie Lantuejoul, Nicolas Lemaitre, Alex Soltermann, Walter Weder, Verena Tischler, Odd Terje Brustugun, Marius Lund-Iversen, Åslaug Helland, Steinar Solberg, Sascha Ansén, Gavin Wright, Benjamin Solomon, Luca Roz, Ugo Pastorino, Iver Petersen, Joachim H Clement, Jörg Sänger, Jürgen Wolf, Martin Vingron, Thomas Zander, Sven Perner, William D Travis, Stefan A Haas, Magali Olivier, Matthieu Foll, Reinhard Büttner, David Neil Hayes, Elisabeth Brambilla, Lynnette Fernandez-Cuesta, Roman K Thomas
Pulmonary large-cell neuroendocrine carcinomas (LCNECs) have similarities with other lung cancers, but their precise relationship has remained unclear. Here we perform a comprehensive genomic (n = 60) and transcriptomic (n = 69) analysis of 75 LCNECs and identify two molecular subgroups: "type I LCNECs" with bi-allelic TP53 and STK11/KEAP1 alterations (37%), and "type II LCNECs" enriched for bi-allelic inactivation of TP53 and RB1 (42%). Despite sharing genomic alterations with adenocarcinomas and squamous cell carcinomas, no transcriptional relationship was found; instead LCNECs form distinct transcriptional subgroups with closest similarity to SCLC...
March 13, 2018: Nature Communications
https://www.readbyqxmd.com/read/29458887/large-cell-neuroendocrine-carcinoma-of-the-endometrium-a-case-report-and-literature-review
#7
Yi-An Tu, Yu-Li Chen, Ming-Chieh Lin, Chi-An Chen, Wen-Fang Cheng
OBJECTIVE: To report a case and review published cases of large cell neuroendocrine carcinoma (LCNEC) of the endometrium. CASE REPORT: A 51-year-old female presented with postmenopausal bleeding and a palpable pelvic mass. An endometrial biopsy showed a malignant mixed Mullerian tumor (MMMT). Suboptimal debulking surgery was performed. The final pathology revealed stage IVB endometrial LCNEC. Post-operative adjuvant chemotherapy with cisplatin and etoposide was administered...
February 2018: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/29454048/new-insights-into-the-molecular-characteristics-of-pulmonary-carcinoids-and-large-cell-neuroendocrine-carcinomas-and-the-impact-on-their-clinical-management
#8
REVIEW
J L Derks, N Leblay, S Lantuejoul, A M Dingemans, E J M Speel, L Fernandez-Cuesta
Carcinoids and large-cell neuroendocrine carcinomas (LCNEC) are rare neuroendocrine lung tumors. Here we provide an overview of the most updated data on the molecular characteristics of these diseases. Recent genomic studies showed that carcinoids generally contain a low mutational burden and few recurrently mutated genes. Most of the reported mutations occur in chromatin-remodeling genes (e.g. MEN1), and few affect genes of the PI3K-AKT-mTOR pathway. Aggressive disease has been related to chromothripsis, DNA-repair gene mutations, loss of OTP/CD44, and upregulation of RET gene expression...
February 14, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29453600/argininosuccinate-synthetase-1-ass1-loss-in-high-grade-neuroendocrine-carcinomas-of-the-urinary-bladder-implications-for-targeted-therapy-with-adi-peg-20
#9
Sounak Gupta, Divya Sahu, John S Bomalaski, Igor Frank, Stephen A Boorjian, Prabin Thapa, John C Cheville, Donna E Hansel
High-grade neuroendocrine carcinomas (HGNECs) of the urinary bladder encompass small cell (SCNEC) and large cell neuroendocrine carcinomas (LCNEC). Currently, recommended initial management is with systemic chemotherapy, followed by consolidative therapy with either radical cystectomy or radiotherapy in patients with localized disease. Nevertheless, survival in this setting remains poor. We therefore evaluated the potential to modify arginine metabolism as an alternative, targeted therapy approach in these carcinomas...
February 16, 2018: Endocrine Pathology
https://www.readbyqxmd.com/read/29413048/distinct-clinicopathologic-features-genomic-characteristics-and-survival-of-central-and-peripheral-pulmonary-large-cell-neuroendocrine-carcinoma-from-different-origin-cells
#10
Fei Zhou, Likun Hou, Ting Ding, Quanming Song, Xiaoxia Chen, Chunxia Su, Wei Li, Guanghui Gao, Shengxiang Ren, Fengying Wu, Jiang Fan, Chunyan Wu, Jie Zhang, Caicun Zhou
BACKGROUND: Pulmonary large cell neuroendocrine carcinoma (LCNEC) represents a rare entity in lung cancer with dismal prognosis. In the present study, we investigated whether there are significant differences between central and peripheral tumors of LCNEC, in terms of clinicopathologic features, genomic profiles, and survival. METHODS AND MATERIALS: A total of 126 cases of LCNEC were included. The tumors with invasion of the segmental and/or lobar bronchus were classified as central LCNEC and those without as peripheral LCNEC...
February 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29391287/the-role-of-systemic-therapy-in-the-management-of-stage-i-large-cell-neuroendocrine-carcinoma-of-the-lung
#11
Lara Kujtan, Varsha Muthukumar, Kevin F Kennedy, John Russell Davis, Ashiq Masood, Janakiraman Subramanian
INTRODUCTION: The optimal treatment strategy for resected stage I large cell neuroendocrine carcinoma of the lung (LCNEC) remains unknown. In this analysis, we evaluate the impact of systemic chemotherapy on patients with stage I LCNEC who have undergone surgical resection. METHODS: The study population included patients who underwent surgical resection for LCNEC and had pathologic stage I disease. We compared overall survival between patients who underwent surgical resection alone, and those who underwent surgical resection plus chemotherapy...
January 29, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29388013/most-high-grade-neuroendocrine-tumours-of-the-lung-are-likely-to-secondarily-develop-from-pre-existing-carcinoids-innovative-findings-skipping-the-current-pathogenesis-paradigm
#12
Giuseppe Pelosi, Fabrizio Bianchi, Elisa Dama, Michele Simbolo, Andrea Mafficini, Angelica Sonzogni, Sara Pilotto, Sergio Harari, Mauro Papotti, Marco Volante, Gabriella Fontanini, Luca Mastracci, Adriana Albini, Emilio Bria, Fiorella Calabrese, Aldo Scarpa
Among lung neuroendocrine tumours (Lung-NETs), typical carcinoid (TC) and atypical carcinoid (AC) are considered separate entities as opposed to large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). By means of two-way clustering analysis of previously reported next-generation sequencing data on 148 surgically resected Lung-NETs, six histology-independent clusters (C1 → C6) accounting for 68% of tumours were identified. Low-grade Lung-NETs were likely to evolve into high-grade tumours following two smoke-related paths...
February 1, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29378266/association-of-pd-l1-expression-with-tumor-infiltrating-immune-cells-and-mutation-burden-in-high-grade-neuroendocrine-carcinoma-of-the-lung
#13
Hye Sook Kim, Jeong Hyeon Lee, Soo Jeong Nam, Chan-Young Ock, Jae-Woo Moon, Chong Woo Yoo, Geon Kook Lee, Ji-Youn Han
BACKGROUND: The immune microenvironment of high-grade neuroendocrine carcinoma (HGNEC) of the lung, including programmed death-ligand 1 (PD-L1) expression, has not been well characterized. METHODS: Based on immunohistochemistry (IHC) results, PD-L1 expression on tumor cells (TC) and tumor-infiltrating immune cells (IC) were scored as follows: TC0 and IC0 were defined as PD-L1 expression <1%, TC1 and IC1 as ≥1% but <10%, TC2 and IC2 as ≥10% but <50%, and TC3 and IC3 as ≥50%...
January 26, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29360191/insulinoma-associated-protein-1-is-a-sensitive-and-specific-marker-of-neuroendocrine-lung-neoplasms-in-cytology-specimens
#14
Erika E Doxtader, Sanjay Mukhopadhyay
BACKGROUND: Recent studies suggest that insulinoma-associated protein 1 (INSM1) is a sensitive and specific marker of neuroendocrine neoplasms. The aims of this study were to determine whether INSM1 can be reliably used in cytology (Cellient) cell blocks, to ascertain whether staining correlates with paired surgical pathology specimens, and to compare its sensitivity and specificity with those of synaptophysin (SYN), chromogranin (CHR), and CD56 for neuroendocrine lung tumors. METHODS: Seventy-four primary lung neoplasms diagnosed on cytology were stained with INSM1, SYN, CHR, and CD56: 41 small cell lung carcinomas (SCLCs), 1 large cell neuroendocrine carcinoma (LCNEC), 10 carcinoid tumors, 11 adenocarcinomas, 9 squamous cell carcinomas, 1 mesothelioma and 1 poorly differentiated non-small cell lung carcinoma, not otherwise specified...
April 2018: Cancer Cytopathology
https://www.readbyqxmd.com/read/29328464/inhibition-of-gli-leads-to-antitumor-growth-and-enhancement-of-cisplatin-induced-cytotoxicity-in-large-cell-neuroendocrine-carcinoma-of-the-lung
#15
Tsukasa Ishiwata, Shunichiro Iwasawa, Takahiro Ebata, Mengmeng Fan, Yuji Tada, Koichiro Tatsumi, Yuichi Takiguchi
Large cell neuroendocrine carcinoma (LCNEC) of the lung is a highly aggressive tumor without established standard treatment. The Hedgehog (Hh) signal, which is critical in embryogenesis, is known to play important roles in maintaining a malignant phenotype in various cancers. The present study explored the possibility of targeting the Hh signal in the treatment of LCNEC by suppressing Hh downstream molecules, Smoothened (Smo) and GLI family zinc finger 1/2 (Gli1/2), in 3 human LCNEC cell lines. Smo inhibitor, BMS-833923, and Gli inhibitor, GANT61, downregulated Gli1 and 2, resulting in the suppression of the cell viability of the 3 cell lines as assessed using an MTT assay...
March 2018: Oncology Reports
https://www.readbyqxmd.com/read/29312580/therapeutic-strategies-and-genetic-profile-comparisons-in-small-cell-carcinoma-and-large-cell-neuroendocrine-carcinoma-of-the-lung-using-next-generation-sequencing
#16
Masaoki Ito, Yoshihiro Miyata, Shoko Hirano, Shingo Kimura, Fumiko Irisuna, Kyoko Ikeda, Kei Kushitani, Yasuhiro Tsutani, Daisuke Ueda, Norifumi Tsubokawa, Yukio Takeshima, Morihito Okada
Small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung are classified as variants of endocrine carcinoma and subdivided into pure or combined type. Clinical benefit of target therapy has not been established in these tumors. This study aimed to compare genetic and clinicopathological features between SCLC and LCNEC or pure and combined types, and explore the possibility of target therapy using next-generation sequencing. In 13 SCLC and 22 LCNEC cases, 72 point mutations, 19 deletions, and 3 insertions were detected...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29302900/epstein-barr-virus-positive-large-cell-neuroendocrine-carcinoma-of-the-nasopharynx-report-of-a-case-with-complete-clinical-and-radiological-response-after-combined-chemoradiotherapy
#17
Jason K Wasserman, Sylvia Papp, Andrew J Hope, Bayardo Perez-Ordóñez
Neuroendocrine carcinomas of the head and neck are rare and are classified as well differentiated, moderately differentiated, and poorly differentiated carcinomas with the latter category being subdivided into small cell and large cell neuroendocrine carcinoma (LCNEC). While most carcinomas in the nasopharynx are associated with Epstein-Barr virus (EBV), there has been only one previous report demonstrating a link between EBV and LCNEC of the nasopharynx. In this report we describe a second case of EBV-positive LCNEC arising in the nasopharynx with bilateral cervical metastases...
January 4, 2018: Head and Neck Pathology
https://www.readbyqxmd.com/read/29259654/a-case-of-large-cell-neuroendocrine-carcinoma-of-the-uterine-cervix-misdiagnosed-as-adenocarcinoma-in-thinprep-cytology-test
#18
Jong-Hee Nam, Jongin Na, Nah-Ihm Kim, Ga-Eon Kim, Chang-Soo Park, Yoo-Duk Choi
Large cell neuroendocrine carcinoma (LCNEC) of uterine cervix is a rare malignancy with aggressive behavior and poor clinical outcome even in its early stage. Few cytopathologic features of cervical LCNEC have been reported previously. A 57-year-old postmenopausal African American female, presented to the local health department with a chief complaint of heavy vaginal bleeding. A 45-year-old female presented with 20 months of vaginal pruritus and foul odor. Cervical malignancy was suspected by pelvis magnetic resonance imaging...
2017: CytoJournal
https://www.readbyqxmd.com/read/29239031/molecular-alterations-of-neuroendocrine-tumours-of-the-lung
#19
REVIEW
Giulio Rossi, Luca Bertero, Caterina Marchiò, Mauro Papotti
Neuroendocrine tumours of the lung comprise low [typical carcinoid (TC)], intermediate [atypical carcinoid (AC)] and high-grade [small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC)] malignancies, while a pre-invasive lesion [diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH)] may generate a subset of peripheral carcinoid tumours. These neoplasms are differentiated conventionally based on mitotic rate, presence of necrosis and cytological details, according to the 2015 World Health Organisation (WHO) classification...
January 2018: Histopathology
https://www.readbyqxmd.com/read/29219616/next-generation-sequencing-approach-to-non-small-cell-lung-carcinoma-yields-more-actionable-alterations
#20
Mitra Mehrad, Somak Roy, Humberto Trejo Bittar, Sanja Dacic
CONTEXT: - Different testing algorithms and platforms for EGFR mutations and ALK rearrangements in advanced-stage lung adenocarcinoma exist. The multistep approach with single-gene assays has been challenged by more efficient next-generation sequencing (NGS) of a large number of gene alterations. The main criticism of the NGS approach is the detection of genomic alterations of uncertain significance. OBJECTIVE: - To determine the best testing algorithm for patients with lung cancer in our clinical practice...
March 2018: Archives of Pathology & Laboratory Medicine
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