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Mixed Neuroendocrine and Non-neuroendocrine Neoplasms (Mi NEN)

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Neuroendocrine Neoplasia Management

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Abstract

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) is the term that the 2019 WHO classification has adopted to decline all digestive neoplasms consisting of at least 30% by a neuroendocrine and a non-neuroendocrine component. MiNENs category represents the results of a plethora of terminologies that have followed over time. At present, MiNENs category encompasses well- and poorly differentiated neuroendocrine components, differently to MANECs term that included only poorly differentiated NECs. MiNENs represent a rare category of neoplasms that account an incidence of 0.01 on 100,000 population per year. The rarity of the disease and the strict diagnostic criteria lead that MiNENs mostly be underestimated. Indeed, in diagnostic process, biopsy could not be representative of whole tumoral mass, underestimating the features of one or both the components. MiNENs virtually can arise from every tissue or organ, but 2019 WHO classification has accepted the term only for digestive NENs, even if some authors put forward the idea of an extension of the term MiNENs to the other neoplasms over GEP tract.

Anyway, due to all the pitfalls around MiNENs, the management of this category of neoplasms is already unknown. In the absence of international guidelines, MiNENs are commonly treated as pure NECs or non-neuroendocrine neoplasms from the same site of origin. On the other hand, mutations in some driver genes seem to be promising in MiNENs, representing a field that should be improved by prospective trials. The analyses of immunohistochemistry and mutational pattern, mostly shared between neuroendocrine and non-neuroendocrine components of MiNENs, lead to the pathogenetic theory of a common precursor, a stem cell undergoing a divergent differentiation. Improving knowledge about the pathogenetic pathways seems to be the key to a better therapeutic management of these rare entities.

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Authors and Affiliations

  1. Division of Gastrointestinal Medical Oncology and Neuroendocrine Division, European Institute of Oncology (IEO), IRCCS, Milan, Italy

    Alice Laffi, Nicola Fazio, Manila Rubino & Francesca Spada

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  1. Alice Laffi
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  2. Nicola Fazio
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  3. Manila Rubino
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  4. Francesca Spada
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Correspondence to Francesca Spada .

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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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Laffi, A., Fazio, N., Rubino, M., Spada, F. (2021). Mixed Neuroendocrine and Non-neuroendocrine Neoplasms (Mi NEN). 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_18

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