A 2007 paper assessed the reliability of CD25 on GI mast cells as a marker of systemic mastocytosis. This study determined mast cell burden in stomach, small intestine and colon of patients with SM and compared it to patients with urticaria pigmentosa, various inflammatory GI conditions and healthy controls. Mast cells were detected using antibodies for tryptase and CD25 (IHC) and counted in 10 hpf and averaged.
In the stomach, SM patients averaged 57 mast cells/hpf, compared to 14/hpf for urticaria pigmentosa patients; 23.7/hpf for other inflammatory GI conditions; and 12/hpf for healthy controls. Conditions other than SM that caused over 20 mast cells/hpf in the stomach were H. pylori positive gastritis and bile reflux esophagus. Some healthy controls also had a count of 20/hpf or higher. See Table 17 for details.
In the small intestine, SM patients averaged 175 mast cells/hpf; urticaria pigmentosa, 22 mast cells/hpf; other inflammatory GI conditions, 20.3 mast cells/hpf; and healthy controls, 27 mast cells/hpf in the duodenum and 32 mast cells/hpf in the terminal ileum. Conditions other than SM that caused over 20 mast cells/hpf in the small intestine were peptic duodenitis, celiac disease, irritable bowel syndrome and eosinophilic enteritis. See Table 18 for details.
In the colon, SM patients averaged 209 mast cells/hpf; urticaria pigmentosa, 13/hpf; other inflammatory GI conditions, 20.4/hpf; and healthy controls, 21/hpf. Conditions other than SM that caused over 20 mast cells/hpf in the colon were ulcerative colitis, Crohn’s colitis, lymphocytic colitis, irritable bowel syndrome and parasitic infection. See Table 19 for details.
| Table 17: Mast cell count in stomach of patients with systemic mastocytosis | ||||||||
| 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. | ||||||||
| Microscopy method: 400x magnification, mast cells counted in 10 hpf and averaged | ||||||||
| Visualization: Tryptase and CD25 (IHC) | ||||||||
| Sample type | Study group: Systemic mastocytosis | Study group: Urticaria pigmentosa | Study group: Inflammatory GI conditions | Control group A:Healthy control | ||||
| Stomach | Average | Range | Average | Range | Average | Range | Average | Range |
| 57 mast cells/hpf | 24-90 mast cells/hpf | 14 mast cells/hpf | 10-17 mast cells/hpf | 23.7 mast cells/hpf | 6-23.3 mast cells/hpf | 12 mast cells/hpf | 5-21 mast cells/hpf | |
| Clusters/dense infiltrates or confluent sheets. | Diffuse scattered cells, no clusters. | Diffuse scattered cells, no clusters. | Diffuse scattered cells, no clusters. | |||||
| Table 18: Mast cell count in small intestine of patients with systemic mastocytosis | ||||||||
| 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. | ||||||||
| Microscopy method: 400x magnification, mast cells counted in 10 hpf and averaged | ||||||||
| Visualization: Tryptase and CD25 (IHC) | ||||||||
| Sample type | Study group: Systemic mastocytosis | Study group: Urticaria pigmentosa | Study group: Inflammatory GI conditions | Control group A:Healthy control | ||||
| Small intestine | Average | Range | Average | Range | Average | Range | Average | Range |
| 175 mast cells/hpf | 74-339 mast cells/hpf | 22 mast cells/hpf | 12-32 mast cells/hpf | 20.3 mast cells/hpf | 17.5-33 mast cells/hpf | 27 mast cells/hpf(duodenum)32 mast cells/hpf (terminal ileum) | 4-51 mast cells/hpf (duodenum)21-40 mast cells/hpf (terminal ileum)
|
|
| Clusters/dense infiltrates or confluent sheets. | Diffuse scattered cells, no clusters. | Diffuse scattered cells, no clusters. | Diffuse scattered cells, no clusters. | |||||
| Table 19: Mast cell count in colon of patients with systemic mastocytosis | ||||||||
| 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. | ||||||||
| Microscopy method: 400x magnification, mast cells counted in 10 hpf and averaged | ||||||||
| Visualization: Tryptase and CD25 (IHC) | ||||||||
| Sample type | Study group: Systemic mastocytosis | Study group: Urticaria pigmentosa | Study group: Inflammatory GI conditions | Control group A:Healthy control | ||||
| Colon | Average | Range | Average | Range | Average | Range | Average | Range |
| 209 mast cells/hpf | 110-301 mast cells/hpf | 13 mast cells/hpf | 8-19 mast cells/hpf | 20.4 mast cells/hpf | 12.1-33.4 mast cells/hpf | 21 mast cells/hpf | 10-31 mast cells/hpf | |
| Clusters/dense infiltrates or confluent sheets. | Diffuse scattered cells, no clusters. | Diffuse scattered cells, no clusters. | Diffuse scattered cells, no clusters. | |||||
| Table 20: Inflammatory GI conditions associated with mast cell over 20/hpf in at least one biopsy | ||
| Stomach | Small intestine | Colon |
| Gastritis from H. pylori infection | Peptic duodenitis | Ulcerative colitis |
| Bile reflux gastropathy | Celiac disease | Crohn’s disease colitis |
| Healthy stomach tissue | Irritable bowel syndrome | Collagenous colitis |
| Eosinophilic enteritis | Lymphocytic colitis | |
| Healthy duodenum and ileum | Irritable bowel syndrome | |
| Parasitic worm infection | ||
| Eosinophilic colitis | ||
| Healthy colon tissue | ||
A 2014 paper (Doyle 2014) summarized results of GI biopsies from various locations for patients with systemic mastocytosis. Mast cell count in SM patients ranged from 20-278/hpf, with an average of 116/hpf. Most biopsies in SM patients contained clusters of mast cells or confluent sheets. 25% of positive biopsies had only one cluster of mast cells. 21% showed multiple clusters within a biopsy while other biopsies from the same region showed no mast cells. Three biopsies from SM patients showed dispersed cells that were CD25+.
In actual practice, many doctors do not take a variety of biopsies, especially if there is no gross abnormality visualized during scoping. This highlights the need to test for CD25. It also provides evidence that while clustering is a defining characteristic of SM, in some tissue spaces, clustering may be absent despite being present elsewhere in the same organ.
Positivity for some markers associated with systemic mastocytosis, but not enough to receive a diagnosis of SM per WHO criteria, yields a diagnosis of monoclonal mast cell activation syndrome (MMAS). Patients with MMAS display clonality of mast cells despite not meeting criteria for SM. In research circles, MMAS is sometimes referred to as preclinical SM. It is possible that MMAS represents a very early stage of SM. MMAS is managed the same way as SM and markers of clonality (25% or more mast cells in a hpf spindle shaped, positivity for CD25 and/or CD2 receptor(s), clustering of mast cells in groups of 15 or more, positivity for CKIT D816V mutation, serum tryptase baseline of 20 ng/ml or higher) should be taken seriously as an indication of proliferative mast cell disease.
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