Introduction and Neuroendocrine Tumors
“Carcinoid Tumors of the Small Intestine” published in 1907 by Siegfried Oberndorfer of the Pathological Institute at the University of Munich, is the first manuscript credited with characterization of what had been, until then, described as a “benign carcinoma”. “Carcinoids” or neuroendocrine tumors, are derived from neuroendocrine cells which themselves are derived from local tissue-specific stem cells, probably through a committed precursor cell. The mechanisms that lead to tumorigenesis are largely unknown.
In general, neuroendocrine tumors (NETs) comprise a heterogeneous group of neoplasia that originates from neuroendocrine cells, which are widely dispersed throughout the body. The vast majority of NETs are localized in the gastrointestinal tract and the lung, although they also occur in other rare sites (e.g., ovary and salivary glands). Those found in the gastrointestinal tract are now referred to as gastroentero-pancreatic neuroendocrine tumors (GEP NETs).
Although carcinoid tumors were initially considered to be relatively slow-growing and benign, it is now apparent that the majority are malignant and they exhibit a wide spectrum of clinical behaviors that range from indolent to aggressive and in some circumstances highly metastatic. Their natural history varies from local invasion and fibrosis in the peritoneal cavity to metastatic spread, most commonly to the liver and lungs. Their biological characteristics (local invasion, fibrosis, and metastatic potential) vary considerably depending on anatomical site, neuroendocrine cell(s) of origin, and secretory products. Most neuroendocrine tumors of the small and large intestines arise in a sporadic manner: others, notably (ECL) cell tumors of the stomach, are found associated with ECL cell hyperplasia, usually due to hypergastrinemia. Little is known about the regulatory proliferation of other gastrointestinal NETs.
NETs were once thought to be relatively rare, but the overall incidence has increased from 1.1 per 100,000 in 1973 to 6.2 per 100,000 in 2005, and similar trends have been observed in other global databases. Much of this increase probably reflects the more widespread use of endoscopy, introduction of more sensitive diagnostic tools, and an overall increased awareness among physicians and patients, but dietary and environmental factors may also be contributing to this trend.
Currently, the 5-year survival rate for gastrointestinal NETs between 1973 and 2005 has ranged from 56.2 % for colon NETs to 87.6% for rectal NETs; disappointingly, the overall 5-year survival has not improved over this time period. The 5-year survival is highly dependent on tumor stage and grade and ranges from only 4.5% in undifferentiated NETs with distant spread to 83.4% in localize, well-differentiated NETs.