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New Concepts in Pathology

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Neuroendocrine Neoplasia Management

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Abstract

Neuroendocrine neoplasms (NENs) originate from the diffuse neuroendocrine system and, therefore, can arise in every part of the body. In two-thirds of cases, they rise in the gastroenteropancreatic (GEP) tract.

NENs represent a heterogeneous group with variable biological and clinical characteristics. They are usually considered rare neoplasms when compared in terms of incidence with the corresponding non-neuroendocrine neoplasms. NENs represent about 1–2% of the total neoplasms of the gastrointestinal (GI) tract but are of particular diagnostic, prognostic, and therapeutic interest.

The main negative prognostic factors of NENs are the site of the primary tumor [pancreatic NENs (PanNENs) generally have a worse prognosis than NENs in the rectum], the stage according to TNM and the World Health Organization (WHO) histopathological classification, which expresses both the morphological aspect of the tumor cells and their proliferative activity in terms of the number of mitoses or proliferation index (Ki-67).

In PanNENs, for example, Ki-67 labeling index correlates significantly with overall survival and also with disease progression in patients with advanced neoplasms and with tumor recurrence in patients undergoing curative surgery. GEP-NENs are all potentially malignant and are distinguished in tumors and carcinomas.

Tumor grading is defined by both morphology and the proliferative index of the tumor (mitotic index and Ki-67).

According to the aforesaid grading rule, WHO 2019 distinguishes: G1-NETs (well-differentiated morphology, <2 mitosis/10 HPF, and/or Ki-67 <3%); G2-NETs (well-differentiated morphology, 2–20 mitosis/10 HPF, and/or Ki-67 between 3% and 20%); G3-NET (well-differentiated morphology, >20 mitosis/10 HPF, and/or Ki-67 >20%); and NEC (poorly differentiated morphology, >20 mitosis/10 HPF, and/or Ki-67 >20%).

MiNENs (mixed neuroendocrine non-neuroendocrine neoplasms) are neoplasms in which the two components, neuroendocrine and non-neuroendocrine, are both represented in at least 30% of the entire tumor.

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Authors and Affiliations

  1. Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

    Massimo Milione, Laura Cattaneo & Alessandro Mangogna

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  1. Massimo Milione
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  2. Laura Cattaneo
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  3. Alessandro Mangogna
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Correspondence to Massimo Milione .

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Editors and Affiliations

  1. Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy

    Giordano Beretta

  2. ASST-Spedali Civili, University of Brescia, BRESCIA, Brescia, Italy

    Alfredo Berruti

  3. Nuclear Medicine, Humanitas Gavazzeni, BERGAMO, Bergamo, Italy

    Emilio Bombardieri

  4. GIT Med Oncology & Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy

    Nicola Fazio

  5. General Surgery Unit, Humanitas Gavazzeni, Bergamo, Italy

    Orlando Goletti

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Milione, M., Cattaneo, L., Mangogna, A. (2021). New Concepts in Pathology. In: Beretta, G., Berruti, A., Bombardieri, E., Fazio, N., Goletti, O. (eds) Neuroendocrine Neoplasia Management. Springer, Cham. https://doi.org/10.1007/978-3-030-72830-4_3

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