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Simon Garinet Institut Cochin INSERM U1016/UMR8104 and CNRS UMR-S8104, Paris, France

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Juliette Nectoux Laboratory of Genetics and Molecular Biology, Hôpital Cochin, Assistance Publique – Hôpitaux de Paris, Paris, France

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Mario Neou Institut Cochin INSERM U1016/UMR8104 and CNRS UMR-S8104, Paris, France

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Eric Pasmant Laboratory of Genetics and Molecular Biology, Hôpital Cochin, Assistance Publique – Hôpitaux de Paris, Paris, France
INSERM UMR745, Biological and Pharmaceutical Sciences University, Université Paris Descartes, Sorbonne Paris Cité, Paris, France

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Anne Jouinot Institut Cochin INSERM U1016/UMR8104 and CNRS UMR-S8104, Paris, France
Department of Medical Oncology, Hôpital Cochin, Assistance Publique – Hôpitaux de Paris, Paris, France

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Mathilde Sibony Department of Pathology, Hôpital Cochin, Assistance Publique – Hôpitaux de Paris, Paris, France

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Lucie Orhant Laboratory of Genetics and Molecular Biology, Hôpital Cochin, Assistance Publique – Hôpitaux de Paris, Paris, France

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Juliana Pipoli da Fonseca Institut Cochin GENOMI’C Platform, Paris, France

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Karine Perlemoine Institut Cochin INSERM U1016/UMR8104 and CNRS UMR-S8104, Paris, France

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Léopoldine Bricaire Department of Endocrinology, Cochin Hospital, Assistance Publique – Hôpitaux de Paris, Paris, France

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Lionel Groussin Institut Cochin INSERM U1016/UMR8104 and CNRS UMR-S8104, Paris, France
Department of Endocrinology, Cochin Hospital, Assistance Publique – Hôpitaux de Paris, Paris, France

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Olivier Soubrane Department of Hepato-Pancreato-Biliary Surgery, Hôpital Beaujon, Assistance Publique – Hôpitaux de Paris, Paris, France

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Bertrand Dousset Department of Digestive and Endocrine Surgery, Assistance Publique – Hôpitaux de Paris, Paris, France

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Rossella Libe Institut Cochin INSERM U1016/UMR8104 and CNRS UMR-S8104, Paris, France
Department of Endocrinology, Cochin Hospital, Assistance Publique – Hôpitaux de Paris, Paris, France

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Franck Letourneur Institut Cochin GENOMI’C Platform, Paris, France

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Jérome Bertherat Institut Cochin INSERM U1016/UMR8104 and CNRS UMR-S8104, Paris, France
Department of Endocrinology, Cochin Hospital, Assistance Publique – Hôpitaux de Paris, Paris, France
Reference Center for Rare Adrenal Diseases, Reference Center for Rare Adrenal Cancer Network COMETE, Hôpital Cochin, AssistancePublique – Hôpitaux de Paris, Paris, France

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Guillaume Assié Institut Cochin INSERM U1016/UMR8104 and CNRS UMR-S8104, Paris, France
Department of Endocrinology, Cochin Hospital, Assistance Publique – Hôpitaux de Paris, Paris, France
Reference Center for Rare Adrenal Diseases, Reference Center for Rare Adrenal Cancer Network COMETE, Hôpital Cochin, AssistancePublique – Hôpitaux de Paris, Paris, France

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Dear Editor, Adrenocortical carcinomas (ACC) are rare but aggressive tumors. Currently, the single curative approach is complete surgery. Prognosis, response to treatment and recurrence remain unpredictable, which stresses the need for new

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Luciana Pinto Brito
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Tamaya Castro Ribeiro
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Madson Q Almeida Unidade de Endocrinologia do Desenvolvimento, Unidade de Suprarrenal, Unidade de Endocrinologia Genética LIM/25, Divisão de Anatomia Patológica do Hospital das Clínicas LIM/14, Laboratorio de Hormonios e Genetica Molecular LIM/42, Faculdade de Medicina da Universidade de Sao Paulo, Avenida Dr Enéas de Carvalho Aguiar, No. 155 PAMB, 2° Andar, Bloco 6, Sao Paulo CEP 05403-900, Brazil

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Alexander Augusto de Lima Jorge Unidade de Endocrinologia do Desenvolvimento, Unidade de Suprarrenal, Unidade de Endocrinologia Genética LIM/25, Divisão de Anatomia Patológica do Hospital das Clínicas LIM/14, Laboratorio de Hormonios e Genetica Molecular LIM/42, Faculdade de Medicina da Universidade de Sao Paulo, Avenida Dr Enéas de Carvalho Aguiar, No. 155 PAMB, 2° Andar, Bloco 6, Sao Paulo CEP 05403-900, Brazil

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Iberê Cauduro Soares Unidade de Endocrinologia do Desenvolvimento, Unidade de Suprarrenal, Unidade de Endocrinologia Genética LIM/25, Divisão de Anatomia Patológica do Hospital das Clínicas LIM/14, Laboratorio de Hormonios e Genetica Molecular LIM/42, Faculdade de Medicina da Universidade de Sao Paulo, Avenida Dr Enéas de Carvalho Aguiar, No. 155 PAMB, 2° Andar, Bloco 6, Sao Paulo CEP 05403-900, Brazil

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Ana Claudia Latronico
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Berenice Bilharinho Mendonca
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Maria Candida Barisson Villares Fragoso Unidade de Endocrinologia do Desenvolvimento, Unidade de Suprarrenal, Unidade de Endocrinologia Genética LIM/25, Divisão de Anatomia Patológica do Hospital das Clínicas LIM/14, Laboratorio de Hormonios e Genetica Molecular LIM/42, Faculdade de Medicina da Universidade de Sao Paulo, Avenida Dr Enéas de Carvalho Aguiar, No. 155 PAMB, 2° Andar, Bloco 6, Sao Paulo CEP 05403-900, Brazil

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Antonio Marcondes Lerario Unidade de Endocrinologia do Desenvolvimento, Unidade de Suprarrenal, Unidade de Endocrinologia Genética LIM/25, Divisão de Anatomia Patológica do Hospital das Clínicas LIM/14, Laboratorio de Hormonios e Genetica Molecular LIM/42, Faculdade de Medicina da Universidade de Sao Paulo, Avenida Dr Enéas de Carvalho Aguiar, No. 155 PAMB, 2° Andar, Bloco 6, Sao Paulo CEP 05403-900, Brazil

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Dear Editor In the last decade, relevant progresses in the molecular basis of adrenocortical tumors (ACTs) were achieved and abnormalities involving growth pathway deregulation were frequently associated with malignancy. Remarkably, upregulation of

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Julie Le Mestre Normandie Univ., UNIROUEN, INSERM, U1239, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Rouen, France

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Michaël Thomas Normandie Univ., UNIROUEN, INSERM, U1239, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Rouen, France

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Céline Duparc Normandie Univ., UNIROUEN, INSERM, U1239, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Rouen, France

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Pierre Val CNRS, UMR 6293, GReD, Inserm U1103, Université Clermont Auvergne, Clermont-Ferrand, France

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Clémence Bures Department of Diabetes, Endocrinology and Metabolic Diseases, Groupe Hospitalier du Havre, Montivilliers, France

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Jean-Jacques Tuech Department of Digestive Surgery, Rouen University Hospital, Rouen, France

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Jean-Christophe Sabourin Department of Pathology, Rouen University Hospital, Rouen, France
Centre for Biological Resources, Rouen University Hospital, Rouen, France

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Stéphanie Baert-Desurmont Department of Genetics, Rouen University Hospital, Rouen, France

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Hervé Lefebvre Normandie Univ., UNIROUEN, INSERM, U1239, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Rouen, France
Centre for Biological Resources, Rouen University Hospital, Rouen, France
Department of Endocrinology, Diabetes and Metabolic Diseases, Rouen University Hospital, Rouen, France
Clinical Investigation Centre, INSERM, CIC1404, Rouen University Hospital, Rouen, France

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Estelle Louiset Normandie Univ., UNIROUEN, INSERM, U1239, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Rouen, France

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Introduction Adrenocortical tumors are frequent in the general population and remain underdiagnosed. Their prevalence increases with aging and has been estimated from 1 to 8.7% in some series ( Reinhard et al. 1996 , Tabarin et al. 2008

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Simon Faillot Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France

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Thomas Foulonneau Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France

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Mario Néou Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France

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Stéphanie Espiard Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France

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Simon Garinet Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France

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Anna Vaczlavik Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France

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Anne Jouinot Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France

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Windy Rondof Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France

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Amandine Septier Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France

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Ludivine Drougat Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France

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Karine Hécale-Perlemoine Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France

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Bruno Ragazzon Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France

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Marthe Rizk-Rabin Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France

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Mathilde Sibony Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France
Department of Pathology, AP-HP, Hôpital Pitié-Salpétrière, Pierre et Marie Curie Université, Paris, France

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Fidéline Bonnet-Serrano Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France
Department of Endocrinology, Center for Rare Adrenal Diseases, AP-HP, Hôpital Cochin, Paris, France
Department of Hormonology, AP-HP, Hôpital Cochin, Paris, France

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Jean Guibourdenche Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France
Department of Hormonology, AP-HP, Hôpital Cochin, Paris, France

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Rosella Libé Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France
Department of Endocrinology, Center for Rare Adrenal Diseases, AP-HP, Hôpital Cochin, Paris, France

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Lionel Groussin Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France
Department of Endocrinology, Center for Rare Adrenal Diseases, AP-HP, Hôpital Cochin, Paris, France

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Bertrand Dousset Department of Endocrine Surgery, AP-HP, Hôpital Cochin, Paris, France

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Aurélien de Reyniès Programme Cartes d’Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, Paris, France

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Jérôme Bertherat Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France
Department of Endocrinology, Center for Rare Adrenal Diseases, AP-HP, Hôpital Cochin, Paris, France

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Guillaume Assié Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France
Department of Endocrinology, Center for Rare Adrenal Diseases, AP-HP, Hôpital Cochin, Paris, France

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Introduction Benign adrenocortical lesions (tumors and hyperplasia) gather a large spectrum of diseases, among them adrenocortical adenomas (ACA), primary bilateral macronodular hyperplasia (PMAH), primary pigmented micronodular dysplasia

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E Louiset INSERM U413, Department of Endocrinology, INSERM U833, Department of Pathology, EA4310, IFRMP 23, Laboratory of Differentiation and Neuronal and Neuroendocrine Communication, University of Rouen, Mont Saint Aignan 76821, France

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K Isvi INSERM U413, Department of Endocrinology, INSERM U833, Department of Pathology, EA4310, IFRMP 23, Laboratory of Differentiation and Neuronal and Neuroendocrine Communication, University of Rouen, Mont Saint Aignan 76821, France

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J M Gasc INSERM U413, Department of Endocrinology, INSERM U833, Department of Pathology, EA4310, IFRMP 23, Laboratory of Differentiation and Neuronal and Neuroendocrine Communication, University of Rouen, Mont Saint Aignan 76821, France

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C Duparc INSERM U413, Department of Endocrinology, INSERM U833, Department of Pathology, EA4310, IFRMP 23, Laboratory of Differentiation and Neuronal and Neuroendocrine Communication, University of Rouen, Mont Saint Aignan 76821, France

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B Cauliez INSERM U413, Department of Endocrinology, INSERM U833, Department of Pathology, EA4310, IFRMP 23, Laboratory of Differentiation and Neuronal and Neuroendocrine Communication, University of Rouen, Mont Saint Aignan 76821, France

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A Laquerrière INSERM U413, Department of Endocrinology, INSERM U833, Department of Pathology, EA4310, IFRMP 23, Laboratory of Differentiation and Neuronal and Neuroendocrine Communication, University of Rouen, Mont Saint Aignan 76821, France

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J M Kuhn INSERM U413, Department of Endocrinology, INSERM U833, Department of Pathology, EA4310, IFRMP 23, Laboratory of Differentiation and Neuronal and Neuroendocrine Communication, University of Rouen, Mont Saint Aignan 76821, France
INSERM U413, Department of Endocrinology, INSERM U833, Department of Pathology, EA4310, IFRMP 23, Laboratory of Differentiation and Neuronal and Neuroendocrine Communication, University of Rouen, Mont Saint Aignan 76821, France

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H Lefebvre INSERM U413, Department of Endocrinology, INSERM U833, Department of Pathology, EA4310, IFRMP 23, Laboratory of Differentiation and Neuronal and Neuroendocrine Communication, University of Rouen, Mont Saint Aignan 76821, France
INSERM U413, Department of Endocrinology, INSERM U833, Department of Pathology, EA4310, IFRMP 23, Laboratory of Differentiation and Neuronal and Neuroendocrine Communication, University of Rouen, Mont Saint Aignan 76821, France

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including carcinomas ( Racz et al . 1992 ). In addition, two cases of adrenocortical tumors associated with elevated plasma renin concentrations have also been reported, indicating that, after its local synthesis, renin can be released in the plasma by

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Aleksander Skardal Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, USA
The Ohio State University and Arthur G. James Comprehensive Cancer Center, Columbus, Ohio, USA
Center for Cancer Engineering, The Ohio State University, Columbus, Ohio, USA

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Hemamylammal Sivakumar Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, USA

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Marco A Rodriguez Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, USA

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Liudmila V Popova Division of Surgical Oncology, The Ohio State University and Arthur G. James Comprehensive Cancer Center, Columbus, Ohio, USA

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Priya H Dedhia The Ohio State University and Arthur G. James Comprehensive Cancer Center, Columbus, Ohio, USA
Center for Cancer Engineering, The Ohio State University, Columbus, Ohio, USA
Division of Surgical Oncology, The Ohio State University and Arthur G. James Comprehensive Cancer Center, Columbus, Ohio, USA

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, adrenal, pancreas, parathyroid, and pituitary glands. Specific examples include thyroid cancers, adrenocortical carcinoma (ACC), neuroendocrine tumors (NETs), paraganglioma, and pheochromocytoma ( Belfiore & Perks 2013 ). With incidences of several

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Enzo Lalli Université Côte d’Azur, Valbonne, France
CNRS UMR7275, Valbonne, France
NEOGENEX CNRS International Associated Laboratory, Valbonne, France
Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France

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Michaela Luconi Department of Experimental and Clinical Biomedical Sciences ‘Mario Serio’, University of Florence, Florence, Italy

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the adrenolytic agent mitotane ( Terzolo et al. 2007 ) and of combination chemotherapy in patients with progressive disease ( Fassnacht et al . 2012 ). Classically, malignancy of adrenocortical tumors (ACTs) has been assessed based on evaluation of

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S G Creemers Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

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R A Feelders Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

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N Valdes Servicio de Endocrinología y Nutrición, Hospital Universitario de Asturias, Oviedo, Spain

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C L Ronchi Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany
Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK

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M Volante Department of Oncology, University of Turin, Orbassano, Turin, Italy

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B M van Hemel Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

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M Luconi Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences ‘Mario Serio’, University of Florence, Florence, Italy

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M H T Ettaieb Departments of Internal Medicine and Endocrinology, Máxima Medical Center, Eindhoven, The Netherlands

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M Mannelli Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences ‘Mario Serio’, University of Florence, Florence, Italy

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M D Chiara Instituto Universitario de Oncologia del Principado de Asturias, Universidad de Oviedo, Oviedo, Spain

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M Fassnacht Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of Würzburg, Würzburg, Germany

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M Papotti Department of Oncology, University of Turin, Orbassano, Turin, Italy

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M N Kerstens Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

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G Nesi Division of Pathological Anatomy, University of Florence, Florence, Italy

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H R Haak Departments of Internal Medicine and Endocrinology, Máxima Medical Center, Eindhoven, The Netherlands

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F J van Kemenade Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands

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L J Hofland Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

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2010 ). Only in rare cases, the adrenal tumor has malignant potential. Adrenocortical carcinoma (ACC) is a highly malignant tumor with 5-year-survival ranging from 16 to 38% ( Kebebew et al. 2006 , Fassnacht et al. 2013 ). The Weiss score (WS

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Isadora P Cavalcante Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France

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Marthe Rizk-Rabin Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France

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Christopher Ribes Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France

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Karine Perlemoine Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France

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Constanze Hantel Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ), University of Zurich (UZH), Zurich, Switzerland
Medizinische Klinik und Poliklinik III, University Hospital Carl Gustav Carus Dresden, Dresden, Germany

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Annabel Berthon Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France

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Jérôme Bertherat Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France
Department of Endocrinology and National Reference Center for Rare Adrenal Disorders, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Paris, France

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Bruno Ragazzon Université de Paris, Institut Cochin, INSERM, CNRS, Paris, France

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endogenous cortisol excess (Cushing syndrome) due to the development of multiple bilateral adrenocortical tumors ( Bouys et al. 2021 ). ARMC5 is located at chromosome 16p11.2, ubiquitously expresses and encodes a protein of 935 amino acids mostly and

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Michaela Luconi Clinical Physiopathology, Human Pathology and Oncology, Departments of

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Monica Mangoni Clinical Physiopathology, Human Pathology and Oncology, Departments of

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Stefania Gelmini Clinical Physiopathology, Human Pathology and Oncology, Departments of

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Giada Poli Clinical Physiopathology, Human Pathology and Oncology, Departments of

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Gabriella Nesi Clinical Physiopathology, Human Pathology and Oncology, Departments of

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Michela Francalanci Clinical Physiopathology, Human Pathology and Oncology, Departments of

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Introduction Adrenocortical carcinoma (ACC) is a rare (1:4×10 6 annual estimated incidence) and aggressive endocrine tumor with a poor prognosis, generally characterized by a limited response to radio/chemotherapy ( Allolio & Fassnacht 2006

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