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Metastatic well-differentiated gastrointestinal neuroendocrine (carcinoid) tumors: Systemic therapy options to control tumor growth and symptoms of hormone hypersecretion

Authors
Jennifer Ang Chan, MD, MPH
Matthew Kulke, MD
Section Editor
Richard M Goldberg, MD
Deputy Editor
Diane MF Savarese, MD

INTRODUCTION

Neuroendocrine cells are distributed widely throughout the body, and neoplasms of these cells, which are termed neuroendocrine tumors (NETs), can arise at many sites. The classification and nomenclature of NETs arising within the digestive system (gastroenteropancreatic NETs) have evolved over the past two decades (see "Pathology, classification, and grading of neuroendocrine tumors arising in the digestive system", section on 'Classification and terminology'):

Well-differentiated NETs show a solid, trabecular, gyriform, or glandular pattern, with fairly uniform nuclei, salt-and-pepper chromatin, and finely granular cytoplasm (picture 1). These tumors were traditionally referred to as carcinoid tumors when they arose in the tubular gastrointestinal tract and pancreatic neuroendocrine (islet cell) tumors when they arose in the pancreas or, in the case of gastrinomas, in the proximal portion of the duodenum. (See "Pathology, classification, and grading of neuroendocrine tumors arising in the digestive system", section on 'Morphology and immunohistochemistry' and "Zollinger-Ellison syndrome (gastrinoma): Clinical manifestations and diagnosis", section on 'Tumor localization'.)

Although gastrointestinal and pancreatic NETs are morphologically similar on routine histologic evaluation, they differ in terms of pathogenesis, biology, and response to therapy.

Poorly-differentiated neuroendocrine tumors, which are called neuroendocrine carcinomas, are high-grade carcinomas that can resemble and have a clinical behavior similar to small cell or large cell neuroendocrine carcinoma of the lung (picture 1) [1]. (See "Pathology, classification, and grading of neuroendocrine tumors arising in the digestive system", section on 'Pathology, tumor classification, and nomenclature' and "High-grade gastroenteropancreatic neuroendocrine carcinoma".)

Systemic treatment options to control tumor growth and symptoms related to hormone hypersecretion for patients with advanced or metastatic well-differentiated NETs arising in the gastrointestinal tract (gastrointestinal neuroendocrine tumors [GINETs], carcinoid tumors) will be discussed in this topic review. Systemic therapy options for pancreatic neuroendocrine tumors and for poorly-differentiated neuroendocrine carcinomas arising in the digestive tract are discussed elsewhere, as are local management options for well-differentiated metastatic gastroenteropancreatic NETs; the clinical presentation, imaging, and biochemical monitoring; pathology, and classification of gastroenteropancreatic NETs; clinical features of primary carcinoid tumors; diagnosis of carcinoid syndrome and tumor localization; the treatment of early-stage carcinoids; bronchial carcinoids; thymic carcinoids; management of symptoms of the carcinoid syndrome; and evaluation and management of neuroendocrine tumors of unknown primary site.

                         

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