Neuroendocrine Tumors: Cellular Origin in the Intestinal Wall
Neuroendocrine tumors (NETs) of the gastrointestinal tract arise from neuroendocrine cells located in the crypts of Lieberkühn within the intestinal mucosa. 1
Cellular Origin and Distribution
NETs originate from neuroendocrine cells (also called Kulchitsky cells) that are distributed throughout the intestinal mucosa in the crypts of Lieberkühn. 1
These cells are part of the diffuse neuroendocrine cell system scattered throughout the gastrointestinal tract, rather than migrating from the neural crest as previously thought. 2
The cells likely arise from pluripotential progenitor cells that develop neuroendocrine characteristics, rather than representing a distinct cell lineage. 2
Histological Layer Specification
The neuroendocrine cells that give rise to NETs are located in the mucosal layer of the intestinal wall, specifically within the epithelial crypts where they are interspersed among other epithelial cells. 1
These cells possess secretory characteristics and express pan-neuroendocrine markers including chromogranin A and synaptophysin. 2
Clinical Implications
Understanding the mucosal origin explains why many NETs are discovered during routine endoscopic screening examinations, as they arise from the innermost layer accessible to endoscopic visualization. 3
The location in the crypts of Lieberkühn means these tumors can be biopsied endoscopically for histopathological diagnosis with immunohistochemical staining for chromogranin A and synaptophysin. 2, 4
Despite their mucosal origin, NETs can demonstrate aggressive behavior with deep invasion through the intestinal wall layers and metastasis to lymph nodes and liver, particularly in midgut locations. 2, 5