Neuroendocrine tumor
Neuroendocrine tumors are neoplasms that arise from cells of the endocrine and nervous systems. Many are benign, while some are malignant. They most commonly occur in the intestine, where they are often called carcinoid tumors, but they are also found in the pancreas, lung and the rest of the body.
Although there are many kinds of NETs, they are treated as a group of tissue because the cells of these neoplasms share common features, such as looking similar, having special secretory granules, and often producing biogenic amines and polypeptide hormones.
NETs are believed to arise from various neuroendocrine cells whose normal function is to serve at the neuroendocrine interface. Neuroendocrine cells are present not only in endocrine glands throughout the body that produce hormones, but are found in all body tissues.
Small intestinal neuroendocrine tumors were first distinguished from other tumors in 1907. They were named carcinoid tumors because their slow growth was considered to be 'cancer-like' rather than truly cancerous.
However, in 1938 it was recognized that some of these small bowel tumors could be malignant. Despite the differences between these two original categories, and further complexities due to subsequent inclusion of other NETs of pancreas and pulmonary origin, all NETs are sometimes subsumed into the term 'carcinoid'.
Enterochromaffin cells, which give rise to carcinoid tumors, were identified in 1897 by Kulchitsky and their secretion of serotonin was established in 1953 when the 'flushing' effect of serotonin had become clinically recognized. Carcinoid heart disease was identified in 1952, and carcinoid fibrosis in 1961.
Neuroendocrine tumors were sometimes called APUDomas because these cells often show amine precursor uptake and decarboxylation to produce biogenic amines such as catecholamines and serotonin. Although this behavior was also part of the disproven hypothesis that these cells might all embryologically arise from the neural crest, neuroendocrine cells sometimes produce various types of hormones and amines, and they can also have strong receptors for other hormones to which they respond.
There have been multiple nomenclature systems for these tumors, and the differences between these schema have often been confusing. Nonetheless, these systems all distinguish between well-differentiated and poorly differentiated NETs. Cellular proliferative rate is of considerable significance in this prognostic assessment.
Although estimates vary, the annual incidence of clinically significant neuroendocrine tumors is approximately 2.5–5 per 100,000; two thirds are carcinoid tumors and one third are other NETs.
The prevalence has been estimated as 35 per 100,000, and may be considerably higher if clinically silent tumors are included. An autopsy study of the pancreas in people who died from unrelated causes discovered a remarkably high incidence of tiny asymptomatic NETs. Routine microscopic study of three random sections of the pancreas found NETs in 1.6%, and multiple sections identified NETs in 10%. As diagnostic imaging increases in sensitivity, such as endoscopic ultrasonography, very small, clinically insignificant NETs may be coincidentally discovered; being unrelated to symptoms, such neoplasms may not require surgical excision.
Additionally, the WHO scheme recognizes mixed tumors with both neuroendocrine and epithelial carcinoma features, such as goblet cell cancer, a rare gastrointestinal tract tumor.
Placing a given tumor into one of categories depends on well-defined histological features: size, lymphovascular invasion, mitotic counts, Ki-67 labelling index, invasion of adjacent organs, presence of metastases and whether they produce hormones.
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