What is a Neuroendocrine Tumor?

The neuroendocrine system consists of highly specialized neuroendocrine cells which act as an interface or junction between the nervous system and the endocrine system. The endocrine system is made up of cells whose function is to produce and secrete hormones into the bloodstream. Hormones are biochemical messengers that help to regulate many different processes within the body. The nervous system is composed of specialized cells (neurons) that control the activities of all body parts. A neuroendocrine cell is a cell which receives neuronal input (a signal from a nerve cell) and releases hormones in response to this signal.

A neuroendocrine tumor can develop anywhere there are neuroendocrine cells. The most common sites from which neuroendocrine tumors arise are the lungs, appendix, small intestine, rectum and pancreas (Yao, Hassan, Phan, Dagohoy, Leary, Mares, Abdalla, Fleming, Vauthey, Rashid, & Evans, 2008). Neuroendocrine tumors that arise in the pancreas are called pancreatic neuroendocrine tumors or islet cell tumors. When neuroendocrine tumors originate in other areas, they are often classified as carcinoid tumors.

Since neuroendocrine tumor cells are derived from neuroendocrine cells, many of these tumor cells can behave like cells they originated from and can secrete a variety of hormones. A functioning neuroendocrine tumor is one that secretes biologically active hormones causing a clinical syndrome. Non-functioning neuroendocrine tumors do not cause clinical syndromes.

Carcinoid tumors and pancreatic neuroendocrine tumors share similarities including often indolent behavior, ability to secrete biologically active hormones, and well-differentiated histology (Reidy, Tang & Saltz, 2009).

Pancreatic neuroendocrine tumors (PNET) are a rare subgroup of tumors found in the pancreas and can be either functional or non-functional. Their appearance in histology sections has little to contribute to their malignant potential since this traditionally depends on the extent of their spread. However, recent WHO classification classifies PNET into well differentiated tumors, well differentiated carcinomas and poorly differentiated carcinomas in an attempt to predict natural history from the pathology report.

They are usually sporadic but they may also appear among other features of genetic syndromes like multiple endocrine neoplasia type I or von Hippel-Lindau disease. Patients usually present with syndromes induced by hormones secreted from functional tumors, or with mass effects from nonfunctional tumors. Functional PNET can secrete biologically active peptides like insulin, gastrin, glucagon, somatostatin, vasoactive intestinal polypeptide (VIP), whereas non-functional tumors also express and secrete peptides like neurotensin or chromogranin A, which are not active.

Most of the PNET are already metastatic by the time they are diagnosed and liver is the most common site of metastasis. Regional lymph node spread is also common. PNET are non-functional in their majority and the absence of a distinct functional syndrome as well as their indolent course and subsequent delay in diagnosis is mainly responsible for the advanced stage at the time of diagnosis. PNET have a 5-year survival that can range from 97% in benign insulinomas to as low as 30% in non-functional metastatic PNET. In addition, more recent data demonstrate that poorly differentiated PNET can have similar prognosis with adenocarcinomas of the gastrointestinal tract.