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Pathology, classification, and grading of neuroendocrine tumors arising in the digestive system

David S Klimstra, MD
Zhaohai Yang, MD, PhD
Section Editor
Richard M Goldberg, MD
Deputy Editor
Diane MF Savarese, MD


Neuroendocrine cells are distributed widely throughout the body. Neuroendocrine neoplasms, defined as epithelial neoplasms with predominant neuroendocrine differentiation, can arise in most organs. While some clinical and pathologic features of these tumors are unique to the site of origin, other characteristics are shared, regardless of site.

The classification and nomenclature of neuroendocrine neoplasms is complex and confusing, in part because most studies have focused on tumors arising in a specific organ system. Site-specific proposals for nomenclature and classification differ in terminology and in the criteria for histologic grading and staging, and this has led to morphologically similar neuroendocrine neoplasms being designated differently, depending on the site of origin. For now, there is no one single system of nomenclature, grading, or staging that is suitable for neuroendocrine neoplasms at all anatomic sites. However, features such as the proliferative rate of the tumor and the extent of local spread are shared by most classification systems.

Neuroendocrine neoplasms of the digestive system arising in the tubular gastrointestinal (GI) tract and the pancreas are relatively rare. The annual incidence in the United States is about 3.65 per 100,000 population [1]. The incidence has been rising over time. (See "Clinical characteristics of carcinoid tumors", section on 'Epidemiology'.)

The terminology of gastroenteropancreatic (GEP) neuroendocrine neoplasms has evolved over the past two decades to reflect a separation into two major categories:

Well-differentiated neuroendocrine tumors (NETs) show a solid, trabecular, gyriform, or glandular pattern, with fairly uniform nuclei, salt-and-pepper chromatin, and finely granular cytoplasm. These tumors were traditionally referred to as carcinoid and pancreatic neuroendocrine (islet cell) tumors. Although carcinoid tumors and pancreatic NETs may have similar characteristics on routine histologic evaluation, they have a different pathogenesis and biology.

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Literature review current through: Nov 2017. | This topic last updated: Dec 20, 2016.
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