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Tiina Vesterinen HUSLAB, Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland

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Teijo Kuopio Department of Biological and Environmental Science, University of Jyväskylä and Department of Pathology, Central Finland Health Care District, Jyväskylä, Finland

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Maarit Ahtiainen Department of Education and Research, Central Finland Central Hospital, Jyväskylä, Finland

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Aija Knuuttila Department of Pulmonary Medicine, Heart and Lung Center, and Cancer Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

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Harri Mustonen Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

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Kaisa Salmenkivi HUSLAB, Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

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Johanna Arola HUSLAB, Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

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Caj Haglund Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Translational Cancer Medicine Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland

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Introduction Pulmonary carcinoid (PC) tumors are low- and intermediate-grade neoplasms that are subdivided into typical carcinoid (TC) and atypical carcinoid (AC) based on the mitotic count and presence of necrosis ( 1 ). PCs belong to

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Samira M Sadowski Thoracic and Endocrine Surgery, University Hospitals of Geneva, Geneva, Switzerland

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Emanuel Christ Department of Endocrinology, Diabetes and Metabolism, University Hospital of Basel, Basel, Switzerland

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Benoit Bédat Thoracic and Endocrine Surgery, University Hospitals of Geneva, Geneva, Switzerland

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Attila Kollár Department of Medical Oncology, Inselspital, University of Bern, Bern, Switzerland

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Wolfram Karenovics Thoracic and Endocrine Surgery, University Hospitals of Geneva, Geneva, Switzerland

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Aurel Perren Institute of Pathology, University of Bern, Bern, Switzerland

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Frédéric Triponez Thoracic and Endocrine Surgery, University Hospitals of Geneva, Geneva, Switzerland

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on behalf of the SwissNET registry
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metastasizes locally to hilar lymph nodes, and also distally to other organs ( 5 ). Regarding the management of pulmonary carcinoids, Caplin and coworkers ( 6 ) have published a recent European Neuroendocrine Tumor Society expert consensus with

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Filippo Ceccato Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, Padova, Italy
Department of Neuroscience DNS, University of Padova, Padova, Italy

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Diego Cecchin Department of Neuroscience DNS, University of Padova, Padova, Italy
Nuclear Medicine Unit, Department of Medicine – DIMED, University-Hospital of Padova, Padova, Italy
Padova Neuroscience Center PNC, University of Padova, Padova, Italy

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Michele Gregianin Nuclear Medicine Unit, Castelfranco Veneto, Italy

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Giacomo Ricci Department of Neuroscience DNS, University of Padova, Padova, Italy

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Cristina Campi Padova Neuroscience Center PNC, University of Padova, Padova, Italy
Department of Mathematics ‘Tullio Levi-Civita’ DM, University of Padova, Padova, Italy

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Filippo Crimì Radiology Unit, Department of Medicine DIMED, University-Hospital of Padova, Padova, Italy

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Marta Bergamo Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, Padova, Italy

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Annibale Versari Nuclear Medicine Unit, Reggio Emilia, Italy

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Carmelo Lacognata Radiology Department, University-Hospital of Padova, Padova, Italy

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Federico Rea Thoracic Surgery Unit, Department of Cardiac, Thoracic and Vascular Sciences, University Hospital of Padova, Padova, Italy

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Mattia Barbot Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, Padova, Italy

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Carla Scaroni Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, Padova, Italy

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Introduction and aim

Ectopic ACTH secretion (EAS) is mostly secondary to thoracic/abdominal neuroendocrine tumours (NETs) or small cell-lung carcinoma (SCLC). We studied the diagnostic accuracy of CT with 68Ga-Dota derivatives (68Ga-SSTR) PET in localizing ACTH-secreting tumor in patients with EAS.

Materials and methods

68Ga-SSTR-PET/CT was performed and compared with the nearest enhanced CT in 18 cases (16 primary and 2 recurrent neoplasms). Unspecific, indeterminate and false-positive uptakes were assessed using conventional imaging, follow-up or histology.

Results

We diagnosed 13 thoracic (9 primary and 2 recurrent bronchial carcinoids, 2 SCLCs) and 1 abdominal (pancreatic NET) tumors. Eight ACTH-secreting tumors were promptly identified at EAS diagnosis (’overt’, four pulmonary carcinoids with two recurrences and two SCLC); six EAS have been discovered during the subsequent follow-up (’covert’, five bronchial carcinoids and one pancreatic NET). At the time of EAS diagnosis, imaging was able to correctly detect the ACTH-secreting tumour in 8/18 cases (6 new diagnosis and 2 recurrences). During the follow-up, six out of initially ten ‘occult’ cases became ‘covert’. At last available follow-up, CT and 68Ga-SSTR-PET/CT were able to diagnose 11/18 and 12/18 ACTH-secreting tumours, respectively (11/14 and 12/14 considering only overt and covert cases, respectively). Four cases have never been localized by conventional or nuclear imaging (’occult EAS’), despite an average follow-up of 5 years.

Conclusion

The 68Ga-SSTR-PET/CT is useful in localizing EAS, especially to enhance positive prediction of the suggestive CT lesions and to detect occult neoplasms.

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Sara Storvall Department of Endocrinology, Abdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

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Helena Leijon Department of Pathology and Huslab, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

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Eeva Ryhänen Department of Endocrinology, Abdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

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Johanna Louhimo Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

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Caj Haglund Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

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Camilla Schalin-Jäntti Department of Endocrinology, Abdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

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Johanna Arola Department of Pathology and Huslab, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

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previously used and verified ( 25 , 26 , 27 , 28 , 33 ) with Western blotting and/or in vitro somatostatin receptor autoradiography. The same antibodies have previously been used by our research group for a study on pulmonary carcinoid tumors ( 23 ) as

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B C M Hermans Department of Pulmonary Diseases, GROW School for Oncology & Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands

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J L Derks Department of Pulmonary Diseases, GROW School for Oncology & Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands

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H J M Groen Department of Pulmonary Diseases, University of Groningen and University Medical Centre, Groningen, The Netherlands

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J A Stigt Department of Pulmonary Diseases, Isala Hospital, Zwolle, The Netherlands

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R J van Suylen Pathology-DNA, Jeroen Bosch Hospital, ‘s Hertogenbosch, The Netherlands

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L M Hillen Department of Pathology, GROW School for Oncology & Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands

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E C van den Broek PALGA Foundation, Utrecht, The Netherlands

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E J M Speel Department of Pathology, GROW School for Oncology & Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands

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A-M C Dingemans Department of Pulmonary Diseases, GROW School for Oncology & Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands

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L Fisseler-Eckhoff A Jonigk D Keller M Ott G Rieker RJ Sinn P Soder S Soltermann A , Interobserver agreement of proliferation index (Ki-67) outperforms mitotic count in pulmonary carcinoids . Virchows Archiv 2013 507 – 513

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Erik Rösner Institute of Pharmacology and Toxicology, Jena University Hospital, Jena, Germany

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Daniel Kaemmerer Department of General and Visceral Surgery, Zentralklinik Bad Berka, Bad Berka, Germany

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Elisa Neubauer Institute of Pharmacology and Toxicology, Jena University Hospital, Jena, Germany

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Jörg Sänger Laboratory of Pathology and Cytology Bad Berka, Bad Berka, Germany

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Amelie Lupp Institute of Pharmacology and Toxicology, Jena University Hospital, Jena, Germany

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H Salmenkivi K Arola J Haglund C PD-1 and PD-L1 expression in pulmonary carcinoid tumors and their association to tumor spread . Endocrine Connections 2019 8 1168 – 1175 . ( https://doi.org/10.1530/EC-19-0308 ) 31 Tsao MS Kerr KM

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Kjell Oberg Uppsala University, Uppsala, Sweden

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Eric Krenning Erasmus Medical Center, Rotterdam, Netherlands

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Anders Sundin Uppsala University, Uppsala, Sweden

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Lisa Bodei Memorial Sloan Kettering Cancer Center, New York, New York, USA

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Mark Kidd Wren Laboratories, Branford, Connecticut, USA

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Margot Tesselaar Netherlands Cancer Institute, Amsterdam, Netherlands

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Valentina Ambrosini University of Bologna, Bologna, Italy

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Richard P Baum Zentralklinik Bad Berka, Bad Berka, Germany

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Matthew Kulke Dana Farber Cancer Institute, Boston, Massachusetts, USA

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Marianne Pavel Charite Hospital, Berlin, Germany

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Jaroslaw Cwikla University of Warmia and Mazury, Olsztyn, Poland

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Ignat Drozdov Wren Laboratories, Branford, Connecticut, USA

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Massimo Falconi Ospedale San Raffaele, Milan, Italy

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Nicola Fazio IEO (European Institute of Oncology), Milan, Italy

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Andrea Frilling Imperial College London, London, UK

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Robert Jensen National Institutes of Health, Bethesda, Maryland, USA

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Klaus Koopmans Martini Ziekenhuis, Groningen, Netherlands

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Tiny Korse Netherlands Cancer Institute, Amsterdam, Netherlands

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Dik Kwekkeboom Erasmus Medical Center, Rotterdam, Netherlands

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Helmut Maecke University Hospital Freiburg, Freiburg, Germany

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Giovanni Paganelli Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy

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Ramon Salazar Instituto Catala d’Oncologia, Barcelona, Spain

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Stefano Severi Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy

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Jonathan Strosberg H. Lee Moffitt Cancer Center, Tampa, Florida, USA

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Vikas Prasad Charite Hospital, Berlin, Germany

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Aldo Scarpa University of Verona, Verona, Italy

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Ashley Grossman Univeristy of Oxford, Oxford, UK

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Annemeik Walenkamp University of Groningen, Groningen, Netherlands

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Mauro Cives H. Lee Moffitt Cancer Center, Tampa, Florida, USA

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Irene Virgolini Medical University Innsbruck, Innsbruck, Austria

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Andreas Kjaer Copenhagen University, Copenhagen, Denmark

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Irvin M Modlin Yale University, New Haven, Connecticut, USA

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neuroendocrine tumors and pulmonary carcinoids . Frontiers of Hormone Research 2015 44 115 – 138 . ( doi:10.1159/000382138 ) 39 Banck MS Kanwar R Kulkarni AA Boora GK Metge F Kipp BR Zhang L Thorland EC Minn KT Tentu

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E T Aristizabal Prada Department of Internal Medicine IV, Campus Grosshadern, University-Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany

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C J Auernhammer Department of Internal Medicine IV, Campus Grosshadern, University-Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany

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expression, suppressed cell growth and caused cell cycle arrest because of a p21 and p27 increase and a cyclin D1 degradation in neuroendocrine gastrointestinal and pulmonary carcinoid cells in vitro ( 172 ). In addition, VPA also suppressed growth of

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