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condition due to aggressive and diffuse disease. These tumors are characterized by aggressive histological features (high Ki-67 index, extensive necrosis, and nuclear atypia) and are classified as neuroendocrine carcinomas (NECs) grade 3 according to the new
Department of Oncology, Haukeland University Hospital, Bergen, Norway
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Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
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Department of Oncology, Haukeland University Hospital, Bergen, Norway
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Department of Oncology, Haukeland University Hospital, Bergen, Norway
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Department of Medical Radiation Physics, Lund University, Lund, Sweden
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Department of Oncology, St.Olavs Hospital, Trondheim, Norway
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Department of Clinical Medicine, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
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Department of Clinical Science, University of Bergen, Bergen, Norway
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Department of Oncology, Haukeland University Hospital, Bergen, Norway
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-differentiated neuroendocrine tumours (NET G3) and poorly differentiated neuroendocrine carcinoma (NEC) ( WHO 2019 ). GEP-NEC have a particularly unfavourable prognosis, with median overall survival <1 year in advanced, treated cases and only 1 month if untreated ( Sorbye et
Department of Clinical Sciences, University of Bergen, Bergen, Norway
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Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia
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of their proliferation index (G1–G3), whereas neuroendocrine carcinoma (NEC) category is used for poorly differentiated neoplasms. The high-grade GEP NEN G3 group (Ki-67 >20%) is therefore now separated into two groups: NET G3 and NEC ( Table 1 ) and
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). Tumor formation occurs in the neuroendocrine organs where constitutively activated RET is expressed. Although neuroendocrine carcinoma (NEC) of the lung has been described in MEN 1 ( Farhandi et al . 1987 ), it has not been described in the MEN2
Department of Biomedical Sciences, Cluster for Molecular Imaging, University of Copenhagen, Copenhagen, Denmark
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Departments of Surgical Gastroenterology and Clinical Endocrinology, Rigshospitalet, Copenhagen, Denmark
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Department of Clinical Science, University of Bergen, Bergen, Norway
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according to the proliferation index Ki-67; ≤2% (Grade 1, G1), 3–20% (G2) and >20% (G3) ( Bosman et al . 2010 ). G1–G2 was collectively referred to as neuroendocrine tumors (NET) and G3 as neuroendocrine carcinoma (NEC). The classification is strongly
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Division of Biostatistics, Department of Epidemiology and Public Health, Albert Einstein College of Medicine, Bronx, New York, USA
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Stanford Genome Technology Center, Stanford, California, USA
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-differentiated G3 NET and poorly differentiated neuroendocrine carcinoma in the most recent version of the WHO classification system, NENs from other primary sites have not been similarly categorized ( Klimstra 2019 ). For example, the recent 2021 WHO
Department of Cancer Biology, Kimmel Cancer Center, Departments of Urology, Radiation Oncology, Thomas Jefferson University, 233 South 10th Street, BLSB 1008, Philadelphia, Pennsylvania 19107, USA
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Department of Cancer Biology, Kimmel Cancer Center, Departments of Urology, Radiation Oncology, Thomas Jefferson University, 233 South 10th Street, BLSB 1008, Philadelphia, Pennsylvania 19107, USA
Department of Cancer Biology, Kimmel Cancer Center, Departments of Urology, Radiation Oncology, Thomas Jefferson University, 233 South 10th Street, BLSB 1008, Philadelphia, Pennsylvania 19107, USA
Department of Cancer Biology, Kimmel Cancer Center, Departments of Urology, Radiation Oncology, Thomas Jefferson University, 233 South 10th Street, BLSB 1008, Philadelphia, Pennsylvania 19107, USA
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Introduction Prostate cancer is the second most common cancer in men worldwide ( Ferlay et al . 2010 ). With >90% of prostate cancers initially diagnosed as acinar adenocarcinomas ( Fine 2012 , Humphrey 2012 ), neuroendocrine carcinomas of the
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considers neuroendocrine carcinomas (NECs) as a single category on the basis of a Ki-67 labeling index (LI) >20% ( Rindi et al. 2010 ). It has recently become apparent that the definition of NEC by the 2010 WHO classification includes a spectrum of
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classification, delineating G3-NETs as a distinct category from the poorly differentiated neuroendocrine carcinoma (NEC) ( Table 1 ) ( Velayoudom-Cephise et al. 2013 , Heetfeld et al. 2015 , Nagtegaal et al. 2020 , Elvebakken et al. 2021 , Luecke et
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differentiated endocrine carcinoma/small cell carcinoma (PDEC) 2. Neuroendocrine carcinoma (NEC) G3 large cell or small cell type 4. Mixed exocrine–endocrine carcinoma (MEEC) 3. Mixed adenoneuroendocrine carcinoma (MANEC) II. Pseudotumour lesions 5. Tumour