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Neoplastic lesions of endocrine cells in the gastrointestinal tract: ten evolving principles as a basis for clinical understanding

Authors Lawrence B, Anderson, Schimmack, Findlay, Kidd, Modlin

Received 4 July 2012

Accepted for publication 4 October 2012

Published 28 December 2012 Volume 2013:3 Pages 1—17


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 6

Ben Lawrence,1,2 Malcolm Anderson,3 Simon Schimmack,1 Michael Findlay,2,3 Mark Kidd,1 Irvin Modlin1

1Department of Surgery, Yale University School of Medicine, New Haven, CT, USA; 2School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, 3Department of Oncology, Auckland District Health Board, Auckland, New Zealand

Abstract: Timely and appropriate diagnosis and treatment of patients with gastroenteropancreatic neuroendocrine neoplasms is a difficult clinical endeavor. The field is particularly dynamic, not only in terms of expanding therapeutic options, but in the classifications and biological principles that underpin good decision-making. Acknowledging the confusion created by past changes and the inevitability of future development, we combine our clinical experience with a review of the literature to frame the current understanding of gastroenteropancreatic neuroendocrine neoplasms in terms of a set of principles that have stabilized in the midst of this change. Firstly, we present five principles that guide classification of neuroendocrine neoplasms; specifically principles of prognostic classification, mechanisms of tumorigenesis, undiagnosed disease burden, clues regarding genetic etiology, and typical clinical presentation. Secondly, we offer five clinical principles upon which to build a therapeutic strategy. Specifically, these treatment principles include the separation of options by tumor cell differentiation, and the site of the primary lesion in well differentiated tumors. Chromogranin A is a moderately useful biomarker. Treatment should only be considered by clinicians in a multidisciplinary team, and in the face of multiple potential therapeutic options without a supporting evidence base, clinical trial enrolment remains imperative. Therefore, we provide a current synopsis of classification of gastroenteropancreatic neuroendocrine neoplasms, and their etiology, clinical presentation, and management in a novel framework of ten relatively stable principles.

Keywords: gastroenteropancreatic neuroendocrine neoplasms, neuroendocrine tumors, epidemiology, molecular targeted therapy, histopathology, grading, staging, carcinoid, tumorigenesis

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