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The archaic distinction between functioning and nonfunctioning neuroendocrine neoplasms is no longer clinically relevant

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Abstract

Background

Neuroendocrine neoplasms (NENs) are increasing in incidence and prevalence. This reflects greater clinical awareness, effective imaging, and increasing pathological diagnostic recognition. Although the identification and treatment of clinical neuroendocrine syndromes are established, there is confusion when a NEN has no discernible clinical symptoms.

Discussion

Nonfunctional tumors are usually diagnosed incidentally and at a later stage largely because either they do not secrete a bioactive product or do so, but in a form that is either inactive or in quantities that have no discernible effect. Nevertheless, the histopathology is indistinguishable from functional NENs, and tumors exhibit somatostatin receptor expression, and positive immunohistochemistry for neuroendocrine cell markers (CgA, NSE/synaptophysin). Similarly, their rates of growth and metastatic behavior are, like other NENs, predictably based on staging and grading (mitotic rate and Ki67 expression). Both types are diagnosed biochemically (CgA) and by imaging in an identical fashion with computed tomography, magnetic resonance imaging, somatostatin receptor scintigraphy, and endoscopic ultrasound. NENs, irrespective of function or bioactive secretory profile, respond with equal efficacy to the same regimen of surgery or antitumor drugs (e.g., somatostatin analogs with or without tyrosine kinase inhibitors/antiangiogenics or cytotoxics) depending on grade. Given the efficacy of somatostatin analogs in increasing progression free survival, nonfunctional NENs should be managed identically to symptomatic NENs. The consideration of NENs as functional or nonfunctional is an archaic clinical concept that should be discarded since the tumors are indistinguishable at a cellular, biological, and morphological level. All current evidences indicate that their diagnosis and treatment should follow the same common principles.

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Acknowledgments

MK was supported in part by NIH: DK080871. BL was supported in part by a grant from the Genesis Oncology Trust, Auckland, New Zealand.

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Authors and Affiliations

  1. Gastrointestinal Pathobiology Group, Yale University School of Medicine, 310 Cedar Street, New Haven, CT, BML212, USA

    Irvin M. Modlin, Ben Lawrence, Simon Schimmack & Mark Kidd

  2. Liver Research Center, Brown University, Providence, RI, 02903, USA

    Steven F. Moss

  3. Department of Gastroenterology, St Olavs Hospital, Norwegian University of Science and Technology, Prinsesse Kristinas gate 1, 7006, Trondheim, Norway

    Bjorn I. Gustafsson

  4. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Prinsesse Kristinas gate 1, 7006, Trondheim, Norway

    Bjorn I. Gustafsson

  5. Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany

    Simon Schimmack

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Modlin, I.M., Moss, S.F., Gustafsson, B.I. et al. The archaic distinction between functioning and nonfunctioning neuroendocrine neoplasms is no longer clinically relevant. Langenbecks Arch Surg 396, 1145–1156 (2011). https://doi.org/10.1007/s00423-011-0794-7

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