Q:

8/14/2013
I have a 32 year-old female with well documented Indolent Systemic Mastocytosis (bone marrow biopsy, serum tryptase quite elevated, immune hystochemical mast cell markers, urticaria pigmentosa, etc). She has the usual GI mastocytosis symptoms of intermittent nausea, vomiting, abdominal pain and occasional diarrhea. She underwent routine endoscopy and colonoscopy and suspicious rectal mucosal biopsies came back with the diagnosis of "proctitis most likely ulcerative colitis". No immune staining for tryptase on the mononuclear inflammatory cells present in the rectal biopsies? IBD/ulcerative colitis? Systemic mastocytosis mimicking IBD? Thanks in advance!

A:

Thank you for your inquiry.

As you can see from the abstracts copied below, mast cells can be present in increased numbers on biopsies of patients with inflammatory bowel disease, including ulcerative colitis. In addition, as you stated, the bowel manifestations of systemic mastocytosis can mimic inflammatory bowel disease.

Thus, for a definitive diagnosis, one would need biopsies. However, in order to distinguish the mast cell infiltrate associated with inflammatory bowel disease from mastocytosis involving the bowel, mast cell markers are required. The most commonly used marker is CD25. The abstracts copied below discuss the value of obtaining CD25 to make this distinction. Its presence indicates a monoclonal mast cell line, and its absence indicates mast cells associated with inflammatory bowel disease. Without it, one can only make a guess as to whether the patient you are describing has both conditions pathologic findins related to her mastocytosis.

My guess, and it would only be a guess without a stain for CD25, is that the inflammatory changes found are probably due to ulcerative proctitis.

It may be that the biopsy specimens previously obtained could be stained at this time for CD25. If so, it may clarify the differential for you.

Thank you again for your inquiry and we hope this response is helpful to you.

Rocz Akad Med Bialymst. 1995;40(1):36-57.
Mast cells in the gastrointestinal tract.
Barczyk M, Debek W, Chyczewski L.
Source
Department of Pathological Anatomy, Medical Academy of Bia³ystok.
Abstract
The morphology and functions of gastrointestinal mast cells (MCs) under physiological and pathological conditions were described. Special attention was paid to the MCs origin, differentiation and morphological and biochemical aspects of their degranulation. Mast cells are important component of normal architecture of the gastrointestinal tract. Many substances released from MCs during degranulation are biologically active and mediate numerous processes: blood flow regulation, epithelial and endothelial permeability, mucosal secretion, gastrointestinal tract motility, immunological events related to the antigens of various origin, angiogenesis, cancer development. Thus MC is often considered as an important agent in pathogenesis of many gastrointestinal diseases. The gastrointestinal diseases which was described in this paper are following: bacterial and parasitic infections, peptic ulcer, ulcerative colitis, Leœniowski-Crohn's disease, inflammatory polyps, intestinal graft-versus-host reaction, neoplastic tumors, mastocytosis, intestinal ischemia.

Am J Surg Pathol. 2007 Nov;31(11):1669-76.
Immunoreactivity for CD25 in gastrointestinal mucosal mast cells is specific for systemic mastocytosis.
Hahn HP, Hornick JL.
Source
Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
Abstract
Systemic mastocytosis (SM) is characterized by the accumulation of neoplastic mast cells in bone marrow and other organs. Gastrointestinal (GI) symptoms are common in both SM and cutaneous mastocytosis [urticaria pigmentosa (UP)], and are usually caused by the release of histamine and other inflammatory mediators. Occasionally, neoplastic mast cells may also directly infiltrate the GI tract. Previous studies have suggested that enumeration of the mast cells in GI biopsies may help establish the diagnosis of SM. However, mast cells have been reported to be increased in various inflammatory diseases, and mast cell density has not been systematically evaluated in other GI disorders. Recently, expression of CD25 by mast cells in bone marrow has been shown to be specific for SM. The purpose of this study was (1) to quantitate and compare mast cells in mucosal biopsies from patients with SM involving the GI tract, UP with GI symptoms, and a control group of diverse inflammatory disorders, and (2) to determine whether immunostaining for CD25 can be used to distinguish neoplastic from reactive mast cells in GI biopsies. Seventeen GI biopsies from 6 patients with SM; 17 GI biopsies from 5 patients with UP; and 157 control cases including 10 each normal stomach, duodenum, terminal ileum, and colon, Helicobacter pylori gastritis, bile reflux gastropathy, peptic duodenitis, celiac disease, Crohn disease, ulcerative colitis, lymphocytic colitis, and collagenous colitis, 20 biopsies from 16 patients with irritable bowel syndrome, 8 biopsies from 5 patients with parasitic infections, and 9 biopsies from 7 patients with eosinophilic gastroenteritis were immunostained for mast cell tryptase, c-kit (CD117), and CD25. Mucosal mast cells were quantitated, and the presence or absence of CD25 expression on mast cells was determined. In SM patients, mast cells in the small intestine and colon numbered >100/high-power field (HPF) in nearly all cases (mean 196/HPF; range 74 to 339). This was significantly higher than in GI biopsies from UP patients (mean 17/HPF; range 8 to 32, P<0.0001) and all inflammatory diseases (P<0.01). Mast cell density in other disorders ranged from a mean of 12/HPF in H. pylori gastritis to 47/HPF in parasitic infections. Interestingly, all SM biopsies (and none of the other cases) contained aggregates or confluent sheets of mast cells. In addition, mast cells in all SM cases were positive for CD25, whereas GI mucosal mast cells in UP and all other control cases were negative. In conclusion, quantitation of mast cells can be helpful to diagnose SM in GI mucosal biopsies, although mast cells are also markedly increased in parasitic infections. Aggregates or sheets of mast cells are only seen in SM. Immunoreactivity for CD25 in GI mucosal mast cells is specific for SM and can be used to confirm the diagnosis.

Am J Surg Pathol. 2006 Nov;30(11):1478-82.
Systemic mastocytosis mimicking inflammatory bowel disease: A case report and discussion of gastrointestinal pathology in systemic mastocytosis.
Bedeir A, Jukic DM, Wang L, Mullady DK, Regueiro M, Krasinskas AM.
Source
Department of Pathology, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA, USA.
Abstract
Gastrointestinal (GI) symptoms are present in up to 80% of patients with systemic mastocytosis (SM). GI symptoms include mainly abdominal pain, diarrhea, nausea, and vomiting. It is believed that most of the GI symptoms are due to the secondary effect of mast cell mediators on the GI tract. Direct involvement of the GI tract by neoplastic mast cell infiltration has not been well documented. We report a case of SM that initially mimicked inflammatory bowel disease based on clinical, radiographic, endoscopic, and histopathologic findings. On routine histologic sections of small bowel and colonic mucosal biopsies, there was expansion of the lamina propria by mononuclear inflammatory cells, foci of erosions with associated acute inflammation, and evidence of chronic mucosal injury with architectural distortion and gland foreshortening. Only on repeat biopsies and with ancillary tests for mast cells was a diagnosis of SM made, with extensive involvement of the GI tract. This is the first reported case of SM presenting as and mimicking inflammatory bowel disease. It is critical that clinicians and pathologists are aware that neoplastic mast cells in patients with SM can infiltrate the mucosa throughout the GI tract and that this infiltration can lead to symptoms and findings that can mimic inflammatory bowel disease.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology