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8 The most recent WHO classification includes NET grade 1, NET grade 2, and NEC these are distinguished from each other on the basis of proliferative index, which is assessed by the percentage of cells that stain positive for Ki-67, and mitotic rate. The WHO classification was revised in 2000 to include benign well-differentiated NET, well-differentiated NET of uncertain behavior, well-differentiated neuroendocrine carcinoma, and poorly differentiated neuroendocrine carcinoma the presence of local invasion or metastases distinguished NET from neuroendocrine carcinoma (NEC). 6 The increasingly imprecise application of the term “carcinoid,” combined with the fact that the minority of these tumors were actually associated with the carcinoid syndrome, led Capella et al 7 to propose the use of the term “neuroendocrine tumor” to refer to all neoplasms of the neuroendocrine system. Under the WHO classification, carcinoid tumors were divided into enterochromaffin cell (classical) carcinoids, gastrin cell carcinoids, and other carcinoids. The first WHO classification system, published in 1980, continued to refer to most tumors of the neuroendocrine system as carcinoid tumors. Although the foregut-midgut-hindgut nomenclature was widely adopted, by the authors' admission, “We have no evidence that this distinction is of fundamental importance, but we consider it a convenient one.” 5 Under this scheme, NETs were classified by embryologic origin into foregut (bronchial, gastric, pancreatic), midgut (bowel from mid-duodenum to midtransverse colon), and hindgut (descending colon and rectum). Continued study revealed an increasingly broad group of tumors with clinical, histologic, and biochemical similarities to the small bowel carcinoids in 1963, Williams and Sandler 5 proposed an expansion of the term “carcinoid” to encompass these diverse neoplasms. In this initial description, these tumors were considered benign, but their variable malignant potential was soon recognized.
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The term “karzinoide” was first used by Oberndorfer 4 to describe a series of six patients who had small bowel tumors. In 1890, Ransom 3 provided the first description of the carcinoid syndrome in a patient who experienced diarrhea and dyspnea aggravated by food and who, on autopsy, had diffuse hepatic metastases and a distal ileal mass. This was followed in 1888 with a report by Lubarsch 2 of two patients who, on autopsy, had multiple small tumors of the ileum. The first description of a small bowel NET was made by Langhans, 1 in 1867, who described a polypoid tumor of the small intestine. Though they share common histologic and biochemical properties, the natural history, malignant potential, and treatment of these tumors can vary dramatically. Neuroendocrine tumors (NETs) are a diverse group of neoplasms that arise from endocrine cells throughout the body.
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