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Overview of Neuroendocrine Tissue Tumors

By Robert J. Kemppainen, DVM, PhD, Professor, Department of Anatomy, Physiology & Pharmacology, College of Veterinary Medicine, Auburn University


Neuroendocrine cells are characterized by their ability to produce and secrete a neuromodulator, transmitter, or hormone. In addition, these cells contain dense core secretory granules, the storage site for the secreted product(s). Neuroendocrine cells are capable of releasing this product in a regulated manner by classic exocytosis. Neuroendocrine cells differ from classic neurons in that they lack axons and synapses. Certain molecules, particularly those of the granin family (eg, chromogranin) are synthesized and stored in neuroendocrine cells and serve as immunohistologic markers.

Previously, neuroendocrine cells were classified as amine precursor uptake and decarboxylation (APUD) cells and were believed to be solely derived from neuroectoderm. However, more recent evidence supports a more diverse embryologic origin.

Tumors that arise from this cell type comprise a family of neuroendocrine tumors, or NETs. Because of the diffuse distribution of cells, particularly within the GI tract, NETs are found in a wide variety of locations. Overall, NETs are rare tumors in people and animals. Some NETs oversecrete their normal product, and the excessive levels result in the observed signs. Other NETs are nonfunctional, and clinical signs instead result from physical forces associated with expansion and/or metastasis.

Examples of NETs include carcinoids, gastroenterohepatic tumors (gastrinoma, insulinoma, glucagonoma), pheochromocytoma of the adrenal gland, medullary carcinoma of the thyroid gland, some pituitary tumors, small-cell lung cancer, multiple endocrine neoplasia (MEN types 1 and 2), and tumors of the chemoreceptor organs. Interestingly, devil facial tumor disease, a devastating transmissible cancer affecting Tasmanian devils (see Tasmanian Devils), appears to be an NET. NETs are identified and classified by their microscopic appearance, the immunohistologic identification of classic neuroendocrine cell markers (such as chromogranin A), and staining for their characteristic transmitter or hormonal product.

Insulinoma and Gastrinoma:

Insulinoma (functional islet cell tumor) is the most common NET in domestic species. For discussions of insulinoma and gastrinoma, see Functional Islet Cell Tumors and see Gastrin-secreting Islet Cell Tumors.


Carcinoids are a heterologous group of NETs that occur in various regions of the GI tract. In dogs and cats, carcinoids have been reported to occur in the stomach. The most common sign reported in affected animals is chronic vomiting. In people (but not yet documented in companion animals), carcinoids serve as a source of serotonin or histamine. Excessive release of these transmitters can cause a syndrome of flushing, hypotension, wheezing, and diarrhea.


Glucagonomas have been found in a small number of dogs. Interestingly, affected animals show cutaneous lesions characterized by a superficial necrolytic dermatitis affecting mucocutaneous junctions, footpads, elbows, or the abdomen.