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Funda İncekara, Koray Aydoğdu, Ebru Sayılır, Selim Şakir Erkmen Gülhan, Funda Demirağ, Sadi Kaya, Göktürk Fındık
BACKGROUND/AIM: Large-cell neuroendocrine carcinoma (LCNEC) of the lung is a relatively uncommon and aggressive subset of pulmonary neuroendocrine tumors, which include typical and atypical carcinoid, and small-cell lung cancer. LCNEC of the lung accounts for no more than 1% of all lung cancers. LCNECs show features of high-grade neuroendocrine tumors and patients with LCNEC have a very poor prognosis. MATERIALS AND METHODS: Twenty-five patients (22 males and 3 females; mean years 60...
December 20, 2016: Turkish Journal of Medical Sciences
Hirokazu Kurohama, Yumi Mihara, Yasumori Izumi, Masatsugu Kamata, Seiji Nagashima, Atsumasa Komori, Yojiro Matsuoka, Nozomi Ueki, Masahiro Nakashima, Masahiro Ito
A 78-year-old man was admitted to our hospital for multiple lung and liver tumors. Initial clinical diagnosis was hepatocellular carcinoma (HCC) with lung metastases because of a high value of serum protein induced by vitamin K absence or antagonist II (PIVKA-II) (6,705 mAU/mL). However, a review of a prior CT showed the lung tumor had existed 6 months before liver tumors were detected. The tumors progressed rapidly and the patient died 37 days after admission. Autopsy revealed that both lung and liver tumors exhibited the histology of large cell neuroendocrine carcinoma (LCNEC)...
January 11, 2017: Pathology International
Alessandra Fabbri, Mara Cossa, Angelica Sonzogni, Mauro Papotti, Luisella Righi, Gaia Gatti, Patrick Maisonneuve, Barbara Valeri, Ugo Pastorino, Giuseppe Pelosi
Optimal histopathological analysis of biopsies from metastases of neuroendocrine tumor (NET) of the lung requires more than morphology only. Additional parameters such as Ki-67 labeling index are required for adequate diagnosis, but few studies have compared reproducibility of different counting protocols and modalities of reporting on biopsies of lung NET. We compared the results of four different manual counting techniques to establish Ki-67 LI. On 47 paired biopsies and surgical specimens from 22 typical carcinoids (TCs), 14 atypical carcinoids (ACs), six large cell neuroendocrine carcinomas (LCNECs), and five small cell carcinomas (SCCs) immunohistochemical staining of Ki-67 antigen was performed...
January 4, 2017: Virchows Archiv: An International Journal of Pathology
Erik Thunnissen, Alain C Borczuk, Douglas B Flieder, Birgit Witte, Mary Beth B Beasley, Jin-Haeng Chung, Sanja Dacic, Sylvie Lantuejoul, Prudence A Russell, Michael den Bakker, Johan Botling, Elisabeth Brambilla, Erienne de Cuba, Kim Geisinger, Kenzo Hiroshima, Alberto Marchevsky, Yuko Minami, Andre Moreira, Andrew G Nicholson, Akihiko Yoshida, Ming-Sound Tsao, Arne Warth, Edwina Duhig, Gang Chen, Yoshihiro Matsuno, William D Travis, Kelly Butnor, Wendy Cooper, Mari Mino-Kenudson, Noriko Motoi, Claudia Poleri, Giuseppe Pelosi, Keith Kerr, Seena C Aisner, Yuichi Ishikawa, Reinhard H Buettner, Naoto Keino, Yasushi Yatabe, Masayuki Noguchi
INTRODUCTION: The current World Health Organization (WHO) classification of lung cancer states that a diagnosis of small cell lung carcinoma (SCLC) can be reliably made on routine histological and cytological grounds, but immunohistochemistry may be required, particularly i) in cases where histologic features are equivocal and ii) in cases where the pathologist wants to increase confidence in diagnosis.. However, reproducibility studies on hematoxylin and eosin-stained slides (H&E) alone for SCLC versus large cell neuroendocrine carcinoma (LCNEC) have shown pairwise kappa scores ranging from 0...
December 17, 2016: Journal of Thoracic Oncology
Takuya Kawabe, Masaaki Yamamoto, Yasunori Sato, Shoji Yomo, Takeshi Kondoh, Osamu Nagano, Toru Serizawa, Takahiko Tsugawa, Hisayo Okamoto, Atsuya Akabane, Kazuyasu Aita, Manabu Sato, Hidefumi Jokura, Jun Kawagishi, Takashi Shuto, Hideya Kawai, Akihito Moriki, Hiroyuki Kenai, Yoshiyasu Iwai, Masazumi Gondo, Toshinori Hasegawa, Soichiro Yasuda, Yasuhiro Kikuchi, Yasushi Nagatomo, Shinya Watanabe, Naoya Hashimoto
OBJECTIVE In 1999, the World Health Organization categorized large cell neuroendocrine carcinoma (LCNEC) of the lung as a variant of large cell carcinoma, and LCNEC now accounts for 3% of all lung cancers. Although LCNEC is categorized among the non-small cell lung cancers, its biological behavior has recently been suggested to be very similar to that of a small cell pulmonary malignancy. The clinical outcome for patients with LCNEC is generally poor, and the optimal treatment for this malignancy has not yet been established...
December 2016: Journal of Neurosurgery
Makoto Murakami, Kanji Katayama, Shigeru Kato, Daisuke Fujimoto, Mitsuhiro Morikawa, Kenji Koneri, Yasuo Hirono, Takanori Goi
BACKGROUND: Large-cell neuroendocrine carcinoma (LCNEC) of the bile duct is extremely rare and is a high-grade type of neuroendocrine tumor with an aggressive clinical course. Here, we report a case of LCNEC of the extrahepatic bile duct. CASE PRESENTATION: An 80-year-old man presented with severe jaundice. Endoscopic retrograde cholangiography and enhanced computed tomography revealed complete obstruction of the common bile duct (CBD) by a dense tumor measuring 1...
December 2016: Surgical Case Reports
Michele Simbolo, Andrea Mafficini, Katarzyna O Sikora, Matteo Fassan, Stefano Barbi, Vincenzo Corbo, Luca Mastracci, Borislav Rusev, Federica Grillo, Caterina Vicentini, Roberto Ferrara, Sara Pilotto, Federico Davini, Giuseppe Pelosi, Rita T Lawlor, Marco Chilosi, Giampaolo Tortora, Emilio Bria, Gabriella Fontanini, Marco Volante, Aldo Scarpa
Next-generation sequencing (NGS) was applied to 148 lung neuroendocrine tumours (LNETs) comprising the four World Health Organization classification categories: 53 typical carcinoid (TCs), 35 atypical carcinoid (ACs), 27 large-cell neuroendocrine carcinomas, and 33 small-cell lung carcinomas. A discovery screen was conducted on 46 samples by the use of whole-exome sequencing and high-coverage targeted sequencing of 418 genes. Eighty-eight recurrently mutated genes from both the discovery screen and current literature were verified in the 46 cases of the discovery screen, and validated on additional 102 LNETs by targeted NGS; their prevalence was then evaluated on the whole series...
November 22, 2016: Journal of Pathology
S Rajkumar, R Iyer, G Culora, G Lane
Large cell neuroendocrine cervical carcinoma (LCNEC) is a rare and aggressive cancer that tends to spread and recur early despite intensive multimodal treatment. Conventional treatment strategies for early stage neuroendocrine tumour (NET) include radical hysterectomy followed by adjuvant chemotherapy. There are only 2 reported cases of fertility sparing treatment for NET. We report on the first case of successful conception and delivery at term following radical trachelectomy for early stage LCNEC.
November 2016: Gynecologic Oncology Reports
Lakshmi Agarwal, Bhawna Gupta, Ayushi Jain
Ovarian Large Cell Neuroendocrine Carcinoma (LCNEC) is a recently described rare entity, which even more rarely occurs in a 'pure' form without any associated surface epithelial-stromal or germ cell component. Cervix metastasis of ovarian LCNEC has not been reported previously. We report here a case of ovarian LCNEC in a 35-year-old female who presented with abdominal pain and amenorrhea. Grossly the left ovary showed a solid cystic tumour measuring 6 cm in diameter. Histological examination showed a pure LCNEC without any associated component, confirmed by immunohistochemistry...
September 2016: Journal of Clinical and Diagnostic Research: JCDR
Kotaro Nagase, Hiromi Kimura, Naomi Yonekura, Shinichi Koba, Takuya Inoue, Yutaka Narisawa
Large-cell neuroendocrine carcinoma (LCNEC) is an uncommon and aggressive neuroendocrine tumor, found mainly in the lung. Although LCNEC has been reported in various organs, LCNEC of the skin is extremely rare, poorly recognized and probably underestimated. Here we report a case of LCNEC of the skin, focusing on the histopathological and ultrastructural findings in detail. The patient was an 85-year-old Japanese woman presented with a mass on her right upper eyelid. Biopsy specimen showed an infiltrative mass with extension into the subcutis...
August 12, 2016: Journal of Cutaneous Pathology
Tomohiro Miyoshi, Shigeki Umemura, Yuki Matsumura, Sachiyo Mimaki, Satoshi Tada, Hideki Makinoshima, Genichiro Ishii, Hibiki Udagawa, Shingo Matsumoto, Kiyotaka Yoh, Seiji Niho, Hironobu Ohmatsu, Keiju Aokage, Tomoyuki Hishida, Junji Yoshida, Kanji Nagai, Koichi Goto, Masahiro Tsuboi, Katsuya Tsuchihara
PURPOSE: Although large-cell neuroendocrine carcinoma (LCNEC) of the lung shares many clinical characteristics with small-cell lung cancer (SCLC), little is known about its molecular features. We analyzed lung LCNECs to identify biologically relevant genomic alterations. EXPERIMENTAL DESIGN: We performed targeted capture sequencing of all the coding exons of 244 cancer-related genes on 78 LCNEC samples [65 surgically resected cases, including 10 LCNECs combined with non-small cell lung cancer (NSCLC) types analyzed separately, and biopsies of 13 advanced cases]...
August 9, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Takeshi Ito, Daisuke Matsubara, Ichidai Tanaka, Kanae Makiya, Zen-Ichi Tanei, Yuki Kumagai, Shu-Jen Shiu, Hiroki J Nakaoka, Shumpei Ishikawa, Takayuki Isagawa, Teppei Morikawa, Aya Shinozaki-Ushiku, Yasushi Goto, Tomoyuki Nakano, Takehiro Tsuchiya, Hiroyoshi Tsubochi, Daisuke Komura, Hiroyuki Aburatani, Yoh Dobashi, Jun Nakajima, Shunsuke Endo, Masashi Fukayama, Yoshitaka Sekido, Toshiro Niki, Yoshinori Murakami
YAP1, the main Hippo pathway effector, is a potent oncogene and is overexpressed in non-small-cell lung cancer (NSCLC); however, the YAP1 expression pattern in small-cell lung cancer (SCLC) has not yet been elucidated in detail. We report that the loss of YAP1 is a special feature of high-grade neuroendocrine lung tumors. A hierarchical cluster analysis of 15 high-grade neuroendocrine tumor cell lines containing 14 SCLC cell lines that depended on the genes of Hippo pathway molecules and neuroendocrine markers clearly classified these lines into two groups: the YAP1-negative and neuroendocrine marker-positive group (n = 11), and the YAP1-positive and neuroendocrine marker-negative group (n = 4)...
October 2016: Cancer Science
Umberto Malapelle, Francesco Morra, Gennaro Ilardi, Roberta Visconti, Francesco Merolla, Aniello Cerrato, Virginia Napolitano, Roberto Monaco, Gianluca Guggino, Guglielmo Monaco, Stefania Staibano, Giancarlo Troncone, Angela Celetti
OBJECTIVES: CCDC6 gene product is a tumor-suppressor pro-apoptotic protein, substrate of ATM, involved in DNA damage response and repair. Altered levels of CCDC6 expression are dependent on post-translational modifications, being the de-ubiquitinating enzyme USP7 responsible of the fine tuning of the CCDC6 stability. Thus, our aim was to investigate CCDC6 and USP7 expression levels in Lung-Neuroendocrine Tumors (L-NETs) to verify if they correlate and may be exploited as novel predictive therapeutic markers...
June 17, 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Takashi Makino, Tetuo Mikami, Yoshinobu Hata, Hajime Otsuka, Satoshi Koezuka, Kazutoshi Isobe, Naobumi Tochigi, Kazutoshi Shibuya, Sakae Homma, Akira Iyoda
BACKGROUND: The prognosis for patients with large cell neuroendocrine carcinoma (LCNEC) of the lung is extremely poor, and optimal treatment strategies have not yet been established. To improve prognoses in patients with LCNEC, this study analyzed immunohistochemical expression and gene mutations of several known molecular targets in LCNECs and compared the expression levels of these targets with those in lung adenocarcinomas. METHODS: Twenty-six patients with primary LCNEC and 40 patients with adenocarcinoma were analyzed...
June 28, 2016: Annals of Thoracic Surgery
Elisa Neubauer, Ralph M Wirtz, Daniel Kaemmerer, Maria Athelogou, Lydia Schmidt, Jörg Sänger, Amelie Lupp
The classification of bronchopulmonary neuroendocrine neoplasms (BP-NEN) into four tumor entities (typical carcinoids (TC), atypical carcinoids (AC), small cell lung cancers (SCLC), large cell neuroendocrine lung carcinomas (LCNEC)) is difficult to perform accurately, but important for prognostic statements and therapeutic management decisions. In this regard, we compared the expression of three proliferation markers, Ki-67, Topoisomerase II alpha (TOP2A), and RacGAP1, in a series of tumor samples from 104 BP-NEN patients (24 TC, 21 AC, 52 SCLC, 7 LCNEC) using different evaluation methods (immunohistochemistry (IHC): Average evaluation, Hotspot evaluation, digital image analysis; RT-qPCR)...
July 5, 2016: Oncotarget
Kyoko Ono, Naho Ruiz Yokota, Emi Yoshioka, Akira Noguchi, Kota Washimi, Kae Kawachi, Yohei Miyagi, Hisamori Kato, Tomoyuki Yokose
A 41-year-old female smoker presented with a vaginal mass. Gynecological examination showed a mass filling the uterine corpus, cervix, and vagina. A total abdominal hysterectomy was performed. Macroscopic findings included a large fragile mass involving the uterine cavity, cervix, and vagina. Histology revealed atypical ducts admixed with solid components consisting of large atypical cells. The initial pathological diagnosis was grade 3 endometrioid adenocarcinoma. The patient was designated as stage II according to the 2008 International Federation of Gynecology and Obstetrics (FIGO) staging...
July 2016: Pathology, Research and Practice
Robert Fred Henry Walter, Fabian Dominik Mairinger, Robert Werner, Claudia Vollbrecht, Thomas Hager, Kurt Werner Schmid, Jeremias Wohlschlaeger, Daniel Christian Christoph
PURPOSE: 25% of all lung cancer cases are neuroendocrine (NELC) including typical (TC) and atypical carcinoid (AC), large-cell neuroendocrine (LCNEC) and small cell lung cancer (SCLC). Prognostic and predictive biomarkers are lacking. EXPERIMENTAL DESIGN: Sixty patients were used for nCounter mRNA expression analysis of the folic-acid metabolism (ATIC, DHFR, FOLR1, FPGS, GART, GGT1, SLC19A1, TYMS) and DNA-repair (ERCC1, MLH1, MSH2, MSH6, XRCC1). Phenotypic classification classified tumors (either below or above the median expression level) with respect to the folic acid metabolism or DNA repair...
April 12, 2016: Oncotarget
Alessandro Tanca, Maria Filippa Addis, Salvatore Pisanu, Marcello Abbondio, Daniela Pagnozzi, Albino Eccher, Guido Rindi, Paolo Cossu-Rocca, Sergio Uzzau, Giuseppe Fanciulli
Here we present a dataset generated using formalin-fixed paraffin-embedded archival samples from two rare lung neuroendocrine tumor subtypes (namely, two atypical carcinoids, ACs, and two large-cell neuroendocrine carcinomas, LCNECs). Samples were subjected to a shotgun proteomics pipeline, comprising full-length protein extraction, SDS removal through spin columns, in solution trypsin digestion, long gradient liquid chromatography peptide separation and LTQ-Orbitrap mass spectrometry analysis. A total of 1260 and 2436 proteins were identified in the AC and LCNEC samples, respectively, with FDR <1%...
June 2016: Data in Brief
Giulio Metro, Biagio Ricciuti, Rita Chiari, Marina Baretti, Lorenzo Falcinelli, Diana Giannarelli, Angelo Sidoni, Giannis Mountzios, Lucio Crinò, Guido Bellezza, Alberto Rebonato, Piero Ferolla, Luca Toschi
BACKGROUND: Among patients with advanced high-grade neuroendocrine carcinoma (HGNEC) of the lung, the optimal therapeutic management is much less established for large cell neuroendocrine carcinomas (LCNECs) than for small cell lung cancers (SCLCs). We evaluated the survival outcomes and incidence of brain recurrence of advanced LCNECs, and compared them with those of a population of SCLCs matched by stage. MATERIALS AND METHODS: Forty-eight unresected stage III HGNECs (16 LCNECs and 32 SCLCs) and 113 stage IV HGNECs (37 LCNECs and 76 SCLCs) were eligible for the analysis...
May 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Natasha Rekhtman, Maria C Pietanza, Matthew D Hellmann, Jarushka Naidoo, Arshi Arora, Helen Won, Darragh F Halpenny, Hangjun Wang, Shaozhou K Tian, Anya M Litvak, Paul K Paik, Alexander E Drilon, Nicholas Socci, John T Poirier, Ronglai Shen, Michael F Berger, Andre L Moreira, William D Travis, Charles M Rudin, Marc Ladanyi
PURPOSE: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a highly aggressive neoplasm, whose biologic relationship to small cell lung carcinoma (SCLC) versus non-SCLC (NSCLC) remains unclear, contributing to uncertainty regarding optimal clinical management. To clarify these relationships, we analyzed genomic alterations in LCNEC compared with other major lung carcinoma types. EXPERIMENTAL DESIGN: LCNEC (n = 45) tumor/normal pairs underwent targeted next-generation sequencing of 241 cancer genes by Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) platform and comprehensive histologic, immunohistochemical, and clinical analysis...
July 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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