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Yasuhiro Miki Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan

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Erina Iwabuchi Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan

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Chihiro Inoue Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan

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Yuto Yamazaki Department of Pathology, Tohoku University Hospital, Sendai, Japan

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Takashi Suzuki Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan
Department of Pathology, Tohoku University Hospital, Sendai, Japan

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cancer is estrogen dependent, ER immunohistochemistry is performed on pathological specimens. The results of this ER immunohistochemical analysis are considered when determining the indications for the endocrine therapies described above. As a type of

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Nele F Lenders Department of Endocrinology, St Vincent’s Hospital, Sydney, NSW, Australia
Garvan Institute of Medical Research, Sydney, NSW, Australia
St Vincent’s Clinical School, University of New South Wales, Sydney, NSW, Australia

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Peter E Earls Department of Anatomical Pathology and Cytopathology, St Vincent’s Pathology, Sydney, NSW, Australia

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Warrick J Inder Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, QLD, Australia
Faculty of Medicine, the University of Queensland, Brisbane, QLD, Australia

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Ann I McCormack Department of Endocrinology, St Vincent’s Hospital, Sydney, NSW, Australia
Garvan Institute of Medical Research, Sydney, NSW, Australia
St Vincent’s Clinical School, University of New South Wales, Sydney, NSW, Australia

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on cell lineage rather than hormonal expression. This followed the WHO 2017 classification recommending the incorporation of transcription factor immunohistochemistry (IHC) into the routine pathological analysis of pituitary tumours ( Lloyd 2017

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Erina Iwabuchi Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan

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Yasuhiro Miki Department of Disaster Obstetrics and Gynecology, International Research Institute of Disaster Science (IRIDes), Tohoku University, Sendai, Japan

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Takashi Suzuki Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan

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Hironobu Sasano Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan

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receptors are usually visualized using immunohistochemistry in formalin-fixed paraffin-embedded (FFPE) tissues. For breast cancers, immunohistochemistry of steroid hormone receptors has been used in clinical practice for the selection of specific therapies

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Stéphanie Larose Division of Endocrinology, Department of Medicine, Centre hospitalier de l’Université de Montréal (CHUM), Université de Montréal, Montréal, QC, Canada

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Dany Rioux Division of Endocrinology, Department of Medicine, Centre hospitalier universitaire régional, Trois-Rivières, QC, Canada

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Roula Albadine Department of Pathology, Centre hospitalier de l’Université de Montréal, Université de Montréal (CHUM), Université de Montréal, Montréal, QC, Canada, Montréal, QC, Canada

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André Lacroix Division of Endocrinology, Department of Medicine, Centre hospitalier de l’Université de Montréal (CHUM), Université de Montréal, Montréal, QC, Canada

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Ectopic adrenocorticotrophic hormone (ACTH) secretion (EAS) is a rare cause of ACTH-dependent Cushing’s syndrome (CS), most often caused by a thoracic neuroendocrine tumor (NET). Large-cell neuroendocrine carcinomas (LCNEC) with EAS are rare and usually present a more severe ACTH secretion and hypercortisolism. We report a 44-year-old non-smoker man, who presented clinical and biochemical evidence of ACTH-dependent CS. Desmopressin 10 μg i.v. produced a 157% increase in ACTH and a 25% increase in cortisol from baseline; there was no stimulation of ACTH or cortisol during the corticotropin-releasing hormone (CRH) test and no suppression with high dose dexamethasone. Pituitary MRI identified a 5 mm lesion, but inferior petrosal venous sinus sampling under desmopressin did not identify a central ACTH source. Thorax and abdominal imaging identified a left lung micronodule. Surgery confirmed a lung LCNEC with strongly positive ACTH immunohistochemistry (IHC) in the primary and lymph node metastasis. The patient was in CS remission after surgery and adjuvant chemotherapy but developed a recurrence 9.5 years later, with LCNEC pulmonary left hilar metastases, ectopic CS, and positive ACTH IHC. This is the first report of LCNEC, with morphologic feature of carcinoid tumor of the lung with ectopic ACTH stimulated by desmopressin. Long delay prior to metastatic recurrence indicates relatively indolent NET. This case report indicates that response to desmopressin, which usually occurs in Cushing’s disease or benign NETs, can occur in malignant LCNEC.

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Erika Peverelli Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

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Donatella Treppiedi Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

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Giovanna Mantovani Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Endocrinology Unit, Milan, Italy

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related to cell-cell adhesion, cadherin signaling, Wnt signaling, and cell proliferation ( Bujko et al. 2019 ). By immunohistochemistry analysis, the cell-cycle inhibitor p27 was found to be significantly reduced, whereas the chaperone HSP90 and the

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Sofia Maria Lider Burciulescu CI Parhon National Institute of Endocrinology, Bucharest, Romania

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Caren Randon Department of Thoracic and Vascular Surgery, Ghent University Hospital & Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, UGent, Ghent, Belgium

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Frederic Duprez Department of Radiotherapy-Oncology, Ghent University Hospital, Ghent Belgium & Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, UGent, Ghent, Belgium

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Wouter Huvenne Department of Head and Neck Surgery, Ghent University Hospital & Department of Head & Skin, Faculty of Medicine and Health Sciences, UGent, Ghent, Belgium

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David Creytens Department of Pathology, Ghent University Hospital, Ghent University & Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, UGent, Ghent, Belgium

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Kathleen B M Claes Center for Medical Genetics, Ghent University Hospital & Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, UGent, Ghent, Belgium

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Robin de Putter Center for Medical Genetics, Ghent University Hospital & Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, UGent, Ghent, Belgium

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Guy T’Sjoen Department of Endocrinology, Ghent University Hospital & Department of Internal Medicine & Pediatrics, Faculty of Medicine and Health Sciences, UGent , Ghent, Belgium

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Corin Badiu CI Parhon National Institute of Endocrinology, Bucharest, Romania
Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

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Bruno Lapauw Department of Endocrinology, Ghent University Hospital & Department of Internal Medicine & Pediatrics, Faculty of Medicine and Health Sciences, UGent , Ghent, Belgium

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SDHB immunohistochemistry results. This study was approved by the Ethical Review Board of Ghent University Hospital (BC-10125) and conducted in accordance with the Declaration of Helsinki. All statistical procedures were performed using Statistical

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Eleanor Fewings Academic Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK

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Serena Khoo Sert Kim Department of Endocrinology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK

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Alexey Larionov Academic Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK

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Alison Marker Department of Histopathology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK

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Olivier Giger Department of Pathology, University of Cambridge, Cambridge, UK

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Ashley Shaw Department of Radiology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK

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Graeme R Clark Academic Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK

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Vasilis Kosmoliaptsis Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

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Benjamin G Challis Department of Endocrinology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK

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Marc Tischkowitz Academic Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK
East Anglian Medical Genetics Service, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK

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Ruth T Casey Academic Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK
Department of Endocrinology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK

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. Tumour immunohistochemistry Immunohistochemical staining was performed with monoclonal mouse anti-human Ki-67 antibody (clone MIB-1, M7240; dilution 1:100; Agilent Technologies) in a Leica BOND-III IHC autostainer, with antigen retrieval performed at pH

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Leo Baxendale-Smith Department of Medical Oncology, Edinburgh Cancer Centre, Western General Hospital, Crewe Road, South, Edinburgh, United Kingdom

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Karim El-Shakankery Department of Medical Oncology, Edinburgh Cancer Centre, Western General Hospital, Crewe Road, South, Edinburgh, United Kingdom

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James Gordon-Smith Department of Interventional Radiology, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom

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Lucy Wall Department of Medical Oncology, Edinburgh Cancer Centre, Western General Hospital, Crewe Road, South, Edinburgh, United Kingdom

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(×40). - Immunohistochemistry – tumour cells express melan A and calretinin; no expression of chromogranin or reaction with an antibody cocktail to cytokeratin. Where the percentage of pleomorphic cells is increased, a higher proportion of tumour cells

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Katherine A English OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK

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Rajesh V Thakker OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK
Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, UK

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Kate E Lines OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK
Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, UK

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transcriptional repressor 1; hMLH1, human MutL homolog 1; 5hmC, 5’ hydroxymethylcytosine; HOPX, HOP homeobox; IGF2, insulin-like growth factor 2; IHC, immunohistochemistry; INA, internexin neuronal intermediate filament protein alpha/alpha-internexin; INS

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Poh Shean Wong Endocrine Unit, Medical Department, Hospital Kuala Lumpur, Malaysia

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Subashini Rajoo Endocrine Unit, Medical Department, Hospital Kuala Lumpur, Malaysia

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Hairuddin Achmad Sankala Radiology Department, Hospital Kuala Lumpur, Malaysia

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Mohamed Badrulnizam Long Bidin Endocrine Unit, Medical Department, Hospital Kuala Lumpur, Malaysia

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examination revealed pituitary metastatic adenocarcinoma. Immunohistochemistry staining showed strong positivity for CK7, CKAE1/ AE3, and EMA and negativity for CK20, ER, PR, mammoglobin, vimentin, and GFAT. Thereafter, she experienced left upper limb pain

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