Mast cells in the GI tract: How many is too many? (Part Four)

The 2009 Walker paper evaluates the mast cell count in patients with irritable bowel syndrome (both diarrhea and constipation predominant forms) and functional dyspepsia (indigestion, upper abdominal pain). This study recorded the total count of mast cells in five fields.  Additionally, two biopsies from different sections of the duodenum were taken for each patient.  I performed some calculations to convert it to mast cells/hpf to be comparable to other data presented in this series.

Mast cells were identified using an antibody to CD117, the CKIT receptor found on the surface of all mast cells. This paper found that the average mast cell count for each patient (averaged between two biopsy sites) was 33/hpf for functional dyspepsia; 45/hpf average for both types of irritable bowel syndrome; 42.7/hpf for irritable bowel syndrome with predominant diarrhea; 47.7/hpf for irritable bowel syndrome with predominant constipation.  The control group of healthy patients demonstrated an average cell count of 29.4/hpf, with a maximum cell count of 46.5 mast cells/hpf. See Table 9 for details.

Table 9: Mast cell count in stomach of patients with irritable bowel syndrome and functional dyspepsia
Walker MM, et al. Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia. Aliment Pharmacol Ther 2009; 29 (7): 765-773.
Microscopy method: 400x magnification, mast cells counted in 5 hpf and totaled

*Note: I made some calculations to yield information that would be comparable to other research (mast cells/hpf).

 

This paper provided total cell counts in 5 hpf for two biopsies for each patient.  For example, patient A had two biopsies with one having 50 mast cells/hpf and the other having 30 mast cells/hpf. I divided each cell count by 5 to give mast cells/hpf. (50/5 = 10 for biopsy 1; 30/5 = 6 for biopsy 2).  I added these together (10+6 = 16) and divided by 2 to get the average (16/2 = 8 mast cells/hpf).

Visualization: CD117 (IHC)
Sample type Study group: Functional dyspepsia Study group: Irritable bowel syndrome (both diarrhea and constipation groups) Study group: Irritable bowel syndrome, diarrhea Study group: Irritable bowel syndrome, constipation Control group: Healthy controls
Duodenum Average Range Average Range Average Range Average Range Average Range
33 mast cells/hpf 39.2-65.4 mast cells/hpf 45 mast cells/hpf 22.2-74.8 mast cells/hpf 42.7 mast cells/hpf 22.2-65.5 mast cells/hpf 47.7 mast cells/hpf 29.7-74.8 mast cells/hpf 29.4 mast cells/hpf 15.2-46.5 mast cells/hpf
Diffuse scattered cells, no clusters. Diffuse scattered cells, no clusters. Diffuse scattered cells, no clusters. Diffuse scattered cells, no clusters. Diffuse scattered cells, no clusters.

 

A 2012 paper by Zare-Mirzaie evaluated colonic tissue of patients with chronic diarrhea.  Cells were detected by two methods: an antibody to tryptase, and through the use of a simple stain, toluidine blue.  The counts presented in table 10 were found using the antibody to tryptase.  Cells were counted in 10 hpf and averaged.

Table 10: Mast cell count in colon of patients with chronic diarrhea
Zare-Mirzaie A, et al. Analysis of colonic mucosa mast cell count in patients with chronic diarrhea. Saudi J Gastroenterol 2012; 18 (5): 322-326.
Microscopy method: 400x magnification, mast cells counted in 10 hpf and averaged
Visualization: Tryptase, toluidine blue
Sample type Study group: Chronic diarrhea Control group A:

Healthy controls

Control group B:

No control group

Colon Average Range Average Range Average Range
21.3 ± 4.8 mast cells/hpf 17-24 mast cells/hpf 14.2 ± 3.4  mast cells/hpf 11-17 mast cells/hpf N/A N/A
Diffuse scattered cells, no clusters. Diffuse scattered cells, no clusters.

 

A 2007 paper by Guilarte mentioned mast cell counts in the jejunum (small intestine) of patients with chronic diarrhea.   Cells were detected with an antibody to CD117. The cells were counted in 10 hpf and averaged.  Please note the correct use of the term “mast cell hyperplasia” rather than “mastocytosis.” See Table 11 for details.

Table 11: Mast cell count in colon of patients with diarrhea predominant irritable bowel syndrome
Guilarte M, et al. Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum. Gut 2007; 56: 203-209.

 

Microscopy method: 400x magnification, mast cells counted in 8 hpf and averaged
Visualization: CD117
Sample type Study group: Irritable bowel syndrome, diarrhea Control group A: Healthy controls
Jejunum Average Range Average Range
34 mast cells/hpf 15.3 mast cells/hpf

 

A 2014 paper by Vivinus-Nebot assessed mast cell counts in the colon of patients with persistent GI symptoms in quiescent (inactive) inflammatory bowel diseases.   Cells were detected with an antibody to CD117. The cells were counted in 3 hpf and averaged.  The mast cell counts in this paper were uniformly low.  This implies that mast cells are involved more directly in the inflammatory GI processes, rather than specifically in diarrhea or constipation. See Table 12 for details.

Table 12: Mast cell count in colon of patients with inactive inflammatory bowel conditions
Vivinus-Nebot M, et al. Functional bowel symptoms in quiescent inflammatory bowel diseases: role of epithelial barrier disruption and low-grade inflammation. Gut 2014; 63: 744-752.
Microscopy method: 400x magnification, mast cells counted in 3 hpf and averaged
Visualization: CD117
Sample type Study group: Irritable bowel syndrome, constipation Study group: Irritable bowel syndrome, diarrhea Study group: Irritable bowel syndrome, mixed Study group: Quiescent Crohn’s disease with irritable bowel syndrome type symptoms
Colon Average Range Average Range Average Range Average Range
12 mast cells/hpf 9-16 mast cells/hpf 12 mast cells/hpf 10-15 mast cells/hpf 12 mast cells/hpf 10-17 mast cells/hpf 12 mast cells/hpf

 

6-16 mast cells/hpf
Distribution not stated. Distribution not stated. Distribution not stated. Distribution not stated.
Sample type Study group: Quiescent Crohn’s disease Study group: Quiescent ulcerative colitis with irritable bowel syndrome type symptoms Study group: Quiescent ulcerative colitis Study group: Healthy controls
Colon Average Range Average Range Average Range Average Range
12 mast cells/hpf 4-16 mast cells/hpf 12 mast cells/hpf 9-15 mast cells/hpf 10 mast cells/hpf 5-15 mast cells/hpf 6 mast cells/hpf 2-9 mast cells/hpf
Distribution not stated. Distribution not stated. Distribution not stated. Distribution not stated.

 

References:

Jakate S, et al. Mastocytic enterocolitis: Increased mucosal mast cells in chronic intractable diarrhea.  Arch Pathol Lab Med 2006; 130 (3): 362-367.

Akhavein AM, et al. Allergic mastocytic gastroenteritis and colitis: An unexplained etiology in chronic abdominal pain and gastrointestinal dysmotility. Gastroenterology Research and Practice (2012): Article ID 950582.

Martinez C, et al. Diarrhoea-predominant irritable bowel syndrome: an organic disorder with structural abnormalities in the jejunal epithelial barrier. Gut 2013; 62: 1160-1168,

Sethi A, et al. Performing colonic mast cell counts in patients with chronic diarrhea of unknown etiology has limited diagnostic use. Arch Pathol Lab Med 2015; 139 (2): 225-232.

Doyle LA, et al. A clinicopathologic study of 24 cases of systemic mastocytosis involving the gastrointestinal tract and assessment of mucosal mast cell density in irritable bowel syndrome and asymptomatic patients. Am J Surg Pathol 2014; 38 (6): 832-843.

Ramsay DB, et al. Mast cells in gastrointestinal disease. Gastroenterology & Hepatology 2010; 6 (12): 772-777.

Zare-Mirzaie A, et al. Analysis of colonic mucosa mast cell count in patients with chronic diarrhea. Saudi J Gatroenterol 2012; 18 (5): 322-326.

Walker MM, et al. Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia. Aliment Pharmacol Ther 2009; 29 (7): 765-773.

Hahn HP, Hornick JL. Immunoreactivity for CD25 in Gastrointestinal Mucosal Mast Cells is Specific for Systemic Mastocytosis. American Journal of Surgical Pathology 2007; 31(11): 1669-1676.

Vivinus-Nebot M, et al. Functional bowel symptoms in quiescent inflammatory bowel diseases : role of epithelial barrier disruption and low-grade inflammation. Gut 2014; 63: 744-752.

Minnei F, et al. Chronic urticaria is associated with mast cell infiltration in the gastroduodenal mucosa. Virchows Arch 2006; 448(3): 262-8.

Hamilton MJ, et al. Mast cell activation syndrome: A newly recognized disorder with systemic clinical manifestations. J Allergy Clin Immunol 2011; 128: 147-152.

Barbara G, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology 2004; 126(3): 693-702.

Guilarte M, et al. Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum. Gut 2007; 56: 203-209.

Dunlop SP, et al.  Age related decline in rectal mucosal lymphocytes and mast cells. European Journal of Gastroenterology and Hepatology 2004; 16(10): 1011-1015.

Afrin LB, Molderings GJ. A concise, practical guide to diagnostic assessment for mast cell activation disease. World J Hematol 2014; 3 (1): 1-17.

Molderings GJ, et al. Mast cell activation disease: a concise, practical guide to diagnostic workup and therapeutic options. J Hematol Oncol 2011; 4 (10).

Akin C, et al. Mast cell activation syndrome: proposed diagnostic criteria. J Allergy Clin Immunol 2010; 126 (6): 1099-1104.

Valent P, et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol 2012: 157 (3): 215-225.