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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
January 23, 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
#8
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...
January 3, 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
#9
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
#10
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
#11
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
#12
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
#13
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...
December 8, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29201450/the-role-of-surgery-in-high-grade-neuroendocrine-tumours-of-the-lung
#14
Stefan Welter, Clemens Aigner, Christian Roesel
High grade lung neuroendocrine tumours are a heterogeneous subtype of pulmonary cancers including small cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC). LCNEC represents approximately 2-3% of lung cancers, whereas SCLC represents 15-20% of lung cancers. Patients with SCLC and LCNEC have a poor prognosis compared with patients with non-small cell lung cancer (NSCLC). LCNEC is treated with primary surgical resection in stages I-II, which is similar to other NSCLCs. Neo-adjuvant treatment in stage III is similar to NSCLC but has not been well studied...
November 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29201447/lung-neuroendocrine-tumors-pathological-characteristics
#15
REVIEW
Luisella Righi, Gaia Gatti, Marco Volante, Mauro Papotti
Lung neuroendocrine tumors (NETs) are a heterogeneous family of neoplasms comprising four histologic types, namely typical and atypical carcinoid (TC and AC), large-cell neuroendocrine and small cell carcinoma (SCC). Classification criteria include the number of mitoses per 2 mm2, the occurrence and extent of necrosis, cytological and histological features and immunohistochemistry for neuroendocrine markers. The classification system and the diagnostic workflow of lung NETs are apparently easy to apply and well established...
November 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29194700/metastatic-laryngeal-large-cell-neuroendocrine-carcinoma-a-rare-case-of-presentation-and-extreme-tumor-burden
#16
Andrew Dunn, Brannon G Broadfoot, Jennifer Hunt, Jennifer R Kaley, Omar Atiq, Narendra B Gutta, Xiaofei Wang, Jerad M Gardner, Sara C Shalin
Large cell neuroendocrine carcinoma (LCNEC) of the larynx is an aggressive form of neuroendocrine carcinoma that affects smokers at an average age of 60 years. LCNEC is characterized by large cells with round to ovoid nuclei distributed in a trabecular or nested growth pattern. Previously, laryngeal LCNEC and atypical carcinoid tumors were considered identical; however, laryngeal LCNEC has been shown to have higher mitotic rates and worse prognosis, which has led to laryngeal LCNEC's being separated from atypical carcinoid and classified as a poorly differentiated neuroendocrine carcinoma in the most recent World Health Organization classification...
December 1, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/29151522/a-case-of-large-cell-neuroendocrine-carcinoma-harboring-an-alk-rearrangement-with-response-to-alectinib
#17
Nobuyoshi Hayashi, Akihisa Fujita, Toyohiro Saikai, Hirotugu Takabatake, Mie Sotoshiro, Kyuutarou Sekine, Akihiko Kawana
Anaplastic lymphoma kinase (ALK) rearrangement is most commonly observed in lung adenocarcinoma in a subset of lung cancer. Large-cell neuroendocrine carcinoma (LCNEC) harboring an ALK rearrangement is very rare. Based on the findings from a transbronchial lung biopsy, a 75-year-old non-smoking woman was diagnosed with LCNEC with multiple liver and bone metastases. After seven cycles of cytotoxic chemotherapy, her genotype testing demonstrated ALK rearrangement. Subsequently, she was administered alectinib and exhibited a partial response...
November 20, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29114469/update-on-large-cell-neuroendocrine-carcinoma
#18
REVIEW
Kenzo Hiroshima, Mari Mino-Kenudson
High-grade neuroendocrine carcinomas of the lung are classified into two categories: large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). While typical cases of LCNEC are morphologically distinct from SCLC, the differentiation between LCNEC and SCLC can be challenging in some cases. In fact, there are borderline high-grade neuroendocrine carcinomas that morphologically fall between LCNEC and SCLC. Growing evidence suggests that LCNEC is a histologically and biologically heterogeneous group of tumors...
October 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29114468/classification-of-pulmonary-neuroendocrine-tumors-new-insights
#19
REVIEW
Giuseppe Pelosi, Angelica Sonzogni, Sergio Harari, Adriana Albini, Enrica Bresaola, Caterina Marchiò, Federica Massa, Luisella Righi, Gaia Gatti, Nikolaos Papanikolaou, Namrata Vijayvergia, Fiorella Calabrese, Mauro Papotti
Neuroendocrine tumors of the lung (Lu-NETs) embrace a heterogeneous family of neoplasms classified into four histological variants, namely typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). Defining criteria on resection specimens include mitotic count in 2 mm2 and the presence or absence of necrosis, alongside a constellation of cytological and histological traits including cell size and shape, nuclear features and overall architecture...
October 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29066508/molecular-subtypes-of-pulmonary-large-cell-neuroendocrine-carcinoma-predict-chemotherapy-treatment-outcome
#20
Jules L Derks, Noémie Leblay, Erik Thunnissen, Robert Jan van Suylen, Michael den Bakker, Harry J M Groen, Egbert F Smit, Ronald Damhuis, Esther C van den Broek, Amélie Charbrier, Matthieu Foll, James D McKay, Lynnette Fernandez-Cuesta, Ernst-Jan M Speel, Anne-Marie C Dingemans
Purpose: Previous genomic studies have identified two mutually exclusive molecular subtypes of large-cell neuroendocrine carcinoma (LCNEC): the RB1 mutated (mostly comutated with TP53) and the RB1 wild-type groups. We assessed whether these subtypes have a predictive value on chemotherapy outcome.Experimental Design: Clinical data and tumor specimens were retrospectively obtained from the Netherlands Cancer Registry and Pathology Registry. Panel-consensus pathology revision confirmed the diagnosis of LCNEC in 148 of 232 cases...
January 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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