A Paucity of Colonic Endocrine Cells Characterizes a Subset of Patients with Malabsorption and/or Diarrhea (M/D)
SJ Ohsie, G Gerney, D Gui, D Kahana, MG Martin, G Cortina. UCLA, Los Angeles, CA
Background: The gut is reputed to be the largest endocrine organ in the body. A generalized absence of enteroendocrine (EE) cells characterizes two malabsorptive diseases, namely enteroendocrine cell dysgenesis (ECD) and autoimmune polyglandular syndrome 1 (APS1). In both diseases, the enterocolonic mucosa demonstrates a paucity of endocrine cells. Because it is far from routine practice to examine small bowel and colonic mucosa for EE cells, the diagnosis of either entity is rarely made by pathologists.
Design: We prospectively examined the colonic mucosa for EE cells by chromogranin A (CGA) immunohistochemistry (IHC) in patients with unexplained chronic malabsorption and nearly normal mucosa. We hypothesized that loss of endocrine cell subsets such as enterochromaffin (EC) cells might be associated with other M/D conditions. Serotonin (5HT) IHC was employed to examine for the subset of EE cells that are EC cells. We additionally hypothesized that a paucity of EE and/or EC cells might be found in mild colonic GVHD. Two methods of enumerating endocrine cells were employed. One was a manual count of endocrine cells and the other was a quantification by image analysis.
Results: There were 7 patients with paucity of endocrine cells recovered over a 9 month period. Three patients were found to have nearly absent EE cells; they were later characterized as having ECD (n=1) and APS1 (n=2) based in large part on the pathological findings. Four patients with reduced EC cells but normal EE cell numbers were also identified. These 4 suffered from diverse conditions such as congenital diarrhea, mild GVHD, toddler diarrhea, and diarrhea post lung transplant. Six cases were suitable for image analysis. The image analysis and manual count methods agreed in 4 of the 6 cases, but low signal intensity hampered image analysis in our hands. The patient with GVHD was found to have markedly reduced EC cells by both techniques. Archival cases of mild colonic GVHD showed no aberration of EC cells, but did show a statistically significant increase in EE cells.
Conclusions: The pathologist can be of great assistance in the diagnosis of APS1 and ECD by examining colonic mucosa for EE cells in patients with unexplained M/D. Loss of EC cells characterizes a subset of acquired M/D conditions. A paucity of EC cells is not seen in most cases of GVHD.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 89, Monday Morning