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

As I mentioned in the previous post, a 2006 paper counted mast cells in the duodenum (part of the small intestine) and colon of patients with treatment resistant chronic diarrhea and compared these counts to patients with known inflammatory GI diseases and to asymptomatic healthy controls.  This paper posited that cell counts over 20 mast cells/hpf represented a distinct phenomenon called mastocytic enterocolitis.  The author felt that mastocytic enterocolitis was distinct from inflammation caused by other GI diseases, such as Crohn’s colitis, ulcerative colitis and celiac disease.

In this paper, the counts for asymptomatic controls ranged from 3-20 cells/hpf and the counts for known inflammatory GI disease ranged from 2-18 mast cells/hpf.  Patients with chronic diarrhea that resisted treatment demonstrated counts ranging from 13-35 mast cells/hpf.  Mast cells were identified by using an antibody to tryptase.

70% of patients with chronic diarrhea without a known cause had over 20 mast cells/hpf. Cells were counted in 10 hpf and averaged.  Counting in multiple fields and averaging generally gives more representative counts. Based upon this study, it was reasonable to assume that mast cells over 20/hpf was higher than normal. See Table 4 for details.

Table 4: Mast cell counts in duodenum and colon of chronic diarrhea patients (Jakate 2006)
Jakate S, et al. Mastocytic enterocolitis: Increased mucosal mast cells in chronic intractable diarrhea.  Arch Pathol Lab Med 2006; 130 (3): 362-367.
Microscopy method: 400x magnification, mast cells counted in 10 hpf and averaged
Visualization: Tryptase (IHC)
Sample type Study group: Intractible chronic diarrhea Control group A: Inflammatory GI disease that causes chronic diarrhea (ie. Crohn’s colitis, ulcerative colitis, gluten sensitive enteropathy) Control group B: Asymptomatic, healthy controls
Duodenum and colon (counts averaged) Average Range Average Range Average Range
25.7 mast cells/hpf 13-35 mast cells/hpf 12.4 mast cells/hpf 2-18 mast cells/hpf 13.3 mast cells/hpf 3-20 mast cells/hpf

 

In a 2012 paper by Akhavein, the stomach, small intestine and colon of patients with a history of atopic/allergic disease were biopsied.  Mast cells were identified using an antibody to CD117, the CKIT receptor found on the surface of all mast cells. The cells were counted in only 1 hpf.

This paper found that the average mast cell count for biopsies from all organs was 37/hpf.  The author posited that given that these patients had a history of allergic conditions, that a count of over 40/hpf described a phenomenon called allergic mastocytic gastroenteritis that was distinct from the previous described mastocytic enterocolitis.  Cells were scattered and not clustered. There was no control group in this study.  See Table 5 and Table 6 for details.

Table 5: Mast cell count in small intestine of patients with GI pain and dysmotility and a history of allergic disease
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.
Microscopy method: Magnification not explicitly stated, assumed 400x, mast cells counted in 1 hpf
Visualization: CD117 (IHC)
Sample type Study group: atopic/allergic history with abdominal pain and GI dysmotility Control group A:

No control group

Control group B:

No control group

Small intestine Average Range Average Range Average Range
57 mast cells/hpf 30-90 mast cells/hpf N/A N/A N/A N/A
Diffuse scattered cells, no clusters.

 

Table 6: Mast cell count in colon of patients with GI pain and dysmotility and a history of allergic disease
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.
Microscopy method: Magnification not explicitly stated, assumed 400x, mast cells counted in 1 hpf
Visualization: CD117 (IHC)
Sample type Study group: Diarrhea predominant IBS Control group A:

Healthy controls

Control group B:

No control group

Colon Average Range Average Range Average Range
37 mast cells/hpf 1-69 mast cells/hpf N/A N/A N/A N/A
Diffuse scattered cells, no clusters.

 

A 2013 paper quantified mast cells in patients with diarrhea predominant irritable bowel syndrome and compared to healthy controls. The patients averaged 26.2 mast cells/hpf in the jejunum, part of the small intestine, while the controls averaged 17.2. Mast cells were identified using an antibody to CD117, the CKIT receptor found on the surface of all mast cells. The cells were likely counted in only 1 hpf as it was not explicitly stated. Distribution of mast cells was not described. See table 7 for details.

 

Table 7: Mast cell count in small intestine of patients diarrhea predominant irritable bowel syndrome
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.
Microscopy method: Magnification not explicitly stated, assumed 400x, number of hpf not explicitly stated, assumed mast cells counted in 1 hpf
Visualization: CD117 (IHC)
Sample type Study group: Diarrhea predominant IBS Control group A:

Healthy controls

Control group B:

No control group

Jejunum Average Range Average Range Average Range
26.2 ± 11.1 mast cells/hpf N/A 17.2 ± 8.8 mast cells/hpf N/A N/A N/A
Diffuse scattered cells, no clusters. Diffuse scattered cells, no clusters.

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.