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Genomics of High-Grade Neuroendocrine Neoplasms: Well-Differentiated Neuroendocrine Tumor with High-Grade Features (G3 NET) and Neuroendocrine Carcinomas (NEC) of Various Anatomic Sites

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Abstract

High-grade neuroendocrine neoplasms (HG-NENs) are clinically aggressive diseases, the classification of which has recently been redefined. They now include both poorly differentiated NENs (neuroendocrine carcinoma, NECs) and high proliferating well-differentiated NENs (called grade 3 neuroendocrine tumors, G3 NETs, in the digestive system). In the last decade, the “molecular revolution” that has affected all fields of medical oncology has also shed light in the understanding of HG NENs heterogeneity and has provided new diagnostic and therapeutic tools, useful in the management of these malignancies. Considering the kaleidoscopic aspects of HG NENs in various anatomical sites, this review systematically addresses the genomic landscape of such neoplasm throughout the more common thoracic and digestive locations, as well as it will consider other rare but not exceptional primary sites, including the skin, the head and neck, and the urogenital system. The revision of the available literature will then be oriented to understand the translational relevance of molecular data, by analyzing conceptual issues, clinicopathological correlations, and unmet needs in this field.

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Authors and Affiliations

  1. Pathology Unit, Department of Medicine and Surgery, University of Insubria, Varese, Italy

    Silvia Uccella & Deborah Marchiori

  2. Institute of Pathology, University Hospital and University of Lausanne, Lausanne, Switzerland

    Stefano La Rosa

  3. Department of Oncology, University of Turin, Torino, Italy

    Jasna Metovic, Marco Volante & Mauro Papotti

  4. Department of Pathology, Gustave Roussy Cancer Campus, Paris, France

    Jean-Yves Scoazec

  5. Department of Pathology, University Health Network, Toronto, ON, Canada

    Ozgur Mete

  6. Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Ozgur Mete

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  1. Silvia Uccella
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Uccella, S., La Rosa, S., Metovic, J. et al. Genomics of High-Grade Neuroendocrine Neoplasms: Well-Differentiated Neuroendocrine Tumor with High-Grade Features (G3 NET) and Neuroendocrine Carcinomas (NEC) of Various Anatomic Sites. Endocr Pathol 32, 192–210 (2021). https://doi.org/10.1007/s12022-020-09660-z

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