Colon
Noninfectious colitis
Mast cell disorders
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PubMed Search: Mastocytic enterocolitis / colitis
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Fernández-Aceñero MJ. Mast cell disorders. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/colonmastocyticenterocolitis.html. Accessed April 19th, 2024.
Definition / general
- Rare condition, described in 2006, occurring in cases of chronic intractable diarrhea (Arch Pathol Lab Med 2006;130:362)
- Not intended as a specific diagnosis (Ann Allergy Asthma Immunol 2008;101:645)
- Helps select patients amenable to specific mast cell targeted therapies
- No uniform or standardized criteria for diagnosis
- Must be distinguished from GI involvement by systemic mastocytosis, a clonal proliferation of mast cells with specific WHO diagnostic criteria
Essential features
- Chronic intractable diarrhea
- Normal endoscopy
- Increase in the number of mast cells in the gastrointestinal biopsies with sheet and nest formation
Terminology
- Also called mastocytic colitis
- Allergic mastocytic gastroenteritis and colitis (Gastroenterol Res Pract 2012;2012:950582)
ICD coding
- ICD-10: K52.9 - noninfective gastroenteritis and colitis, unspecified
Epidemiology
- Chronic diarrhea is a frequent health problem, affecting 5 - 10% of the adult population (Dig Dis 2018;36:409)
- Despite normal colonoscopy, biopsy can reveal abnormalities in almost 30% of cases (20% corresponding to microscopic colitis)
- No gender differences
- Any age
Sites
- Mast cells can be increased anywhere along the gastrointestinal tract
- The most important differences from controls and other disorders are found in the left colon
Pathophysiology
- Mast cells are immunological cells derived from a CD34+ progenitor in the bone marrow
- They are granulated and measure ~20 microns
- They can be activated through IgE dependent (allergic) and IgE independent pathways
- 2 types, according to granule contents: those containing only tryptase and those that also contain chymase and carboxypeptidase
- In the normal mucosa, the tryptase containing mast cells are located in the mucosa (reactive), while the chymase containing ones are mainly submucosal (constitutive)
- They act on the regulation of intestinal permeability, secretion, peristalsis, immunity and angiogenesis
- Upon activation, mast cells are involved in allergies, anaphylaxis, gastrointestinal disorders, malignancies and cardiovascular diseases (Cancers (Basel) 2021;13:3316)
Etiology
- Unclear
- Some patients have a history of allergies
Clinical features
- Chronic intractable diarrhea with normal endoscopy
- Can also be associated with abdominal pain or bloating
Diagnosis
- Based on the clinical history and confirmed by histopathology
Case reports
- 21 year old healthy woman with a 6 month history of diarrhea, abdominal pain and weight loss (Gastroenterol Hepatol 2017;40:467)
- 39 year old man with a longstanding history of diarrhea alternating with constipation, suggestive of irritable bowel disease (J Gastrointestin Liver Dis 2018;27:327)
- 70 year old man with a 3 month history of diarrhea (Intest Res 2016;14:280)
Treatment
- Antihistamines (H1 and H2)
- Mast cell stabilizers, including cromolyn
- Steroids (e.g., prednisone, budesonide) (J Gastrointestin Liver Dis 2018;27:327)
- Inhibitors of mast cell mediators, inhibitors of tryptase and chymase
- Leukotriene antagonists (e.g., montelukast, zileuton)
- Kinase inhibitor (e.g., imatinib, nilotinib, dasatinib)
Gross description
- Normal mucosa on endoscopy
Microscopic (histologic) description
- Normal mucosal architecture
- Increased number of mast cells in the lamina propria
- Might be associated with an increase in eosinophils
- Scattered mast cells but also nests and sheets
- Sometimes presence of a subepithelial band of mast cells
- Hard to recognize in routine H&E stained slides
- Controversy regarding the cutoff value for mast cells
- Most reports recommend more than 20 mast cells/high power field (HPF), although cutoff can be different for the left and right colon and other gastrointestinal locations
- Lack of standardization for counting
- Routine mast cell counting is not recommended at this time
- Significant overlap exists between mast cell counts in asymptomatic control patients and patients with suspected mastocytic enterocolitis, arguing against the clinical utility of routinely counting mast cells in colonic biopsies (Am J Surg Pathol 2014;38:832)
- Patients with gastrointestinal disorders, other than mastocytic enterocolitis showing increases in mast cells, can also benefit from mast cell stabilizing therapies
Microscopic (histologic) images
Contributed by M.J. Fernández-Aceñero, M.D., Ph.D.
Slight inflammatory infiltration
Eosinophils in the infiltrate
KIT expression
Increased mast cells
Positive stains
- Immunohistochemistry is necessary for reliable mast cell counting
- Mast cells are positive for KIT (CD117) (Cells 2021;10:444)
- Also express tryptase (Immunol Allergy Clin North Am 2014;34:315)
Negative stains
Sample pathology report
- Large bowel, endoscopic biopsy:
- Large bowel mucosa with slight increase in lamina propria mast cells (see comment)
- Comment: Large bowel mucosa with a slight expansion of the lamina propria related to an increase in the number of mast cells in the immunohistochemical stains for KIT. The mast cell count is 36 per high power field.
Differential diagnosis
- Systemic mastocytosis (SM):
- Gastrointestinal tract can be involved in 60 - 80% of SM patients (Cancers (Basel) 2021;13:3316)
- Major criterion to diagnose SM is the presence of multifocal clusters of spindled mast cells in the bone marrow, absent in mastocytic colitis (Am J Hematol 2021;96:508)
- WHO recognizes several subtypes:
- Indolent / smoldering SM
- Advanced
- Aggressive SM
- SM with associated hematological neoplasms
- Mast cell leukemia
- Irritable bowel syndrome (IBS):
- Mast cells can be significantly increased in IBS population
- Overlap in the number of mast cells between groups is too large to be useful in clinical practice (Dig Dis 2018;36:409)
- Inflammatory bowel disease (IBD):
- Increase and degranulation of mast cells can release inflammatory mediators that initiate and maintain neutrophilic infiltration
- Typical clinical, endoscopic and histopathological data of Crohn's disease or ulcerative colitis
- Mast cells can be increased in varying grades in many other gastrointestinal pathologies but history, endoscopy and other histopathological features should allow differential:
- Collagenous colitis:
- Typical thickening of the basement membrane
- Motility disorders (Chagas disease, Hirschsprung disease):
- Absence of ganglion cells in the nerves
- Radiation associated enteritis / colitis:
- History
- Diverticular disease:
- History and endoscopy
- Collagenous colitis:
Board review style question #1
The picture shows KIT immunostaining in a large bowel biopsy of a patient with chronic diarrhea. Which of the following statements regarding KIT immunostaining is true?
- Mast cell counts under 20/HPF should never be reported
- Should be performed in all large bowel biopsies with normal endoscopy
- The presence of a subepithelial band of mast cells is diagnostic of mastocytic enterocolitis
- There are clear differences between normal population and patients with different diseases in the number of mast cells
- There are no uniform criteria for the diagnosis of mastocytic enterocolitis
Board review style answer #1
E. There are no uniform criteria for the diagnosis of mastocytic enterocolitis. To date, the criteria for the diagnosis of mastocytic enterocolitis are not standardized and although most authors recommend 20/HPF, the most recent guidelines and meta analysis emphasize the large overlap in the mast cell numbers between controls and patients with diarrhea and other gastrointestinal pathologies. On the other hand, patients with lower mast cell counts can benefit from therapy, so it is recommended to report the absolute number of mast cells per HPF.
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Reference: Mastocytic enterocolitis
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Board review style question #2
Mastocytic enterocolitis is a(n)
- Clearly defined clinicopathological disease
- Diagnosis that can only be made on imaging
- Disease of young allergic people with a clear clinical phenotype
- Orientative diagnosis to help select patients that are candidates for targeted therapies
- Outdated entity that no longer exists
Board review style answer #2
D. Mastocytic enterocolitis is an orientative diagnosis to help select patients that are candidates for targeted therapies. This diagnosis is almost never certain on pure histopathological criteria and is only useful to select candidates to mast cell stabilizing therapies, as a significant number can respond to them.
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Reference: Mastocytic enterocolitis
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