Performing Colonic Mast Cell Counts in Patients With Chronic Diarrhea of Unknown Etiology Has Limited Diagnostic Use

Abstract

Context.-Mastocytic enterocolitis is a recently described entity defined by chronic diarrhea of unknown etiology and normal colon biopsy results with increased mast cells (MCs) seen on special stains. These patients may benefit from mast cell stabilizers; however, the clinical utility of MC counts remains unknown.Objective.-To determine the clinical utility of colonic MC counts on normal biopsies in patients with chronic diarrhea of unknown etiology.Design.-Blinded MC counts using a c-Kit stain were performed in 76 consecutive patients with chronic diarrhea of unknown etiology who had normal colon biopsy results and in 89 consecutive control patients presenting for screening colonoscopy. Mast cells were counted per single high-power field in the highest-density area. A t test was used to compare the counts, and receiver operating characteristic curves were generated to examine sensitive and specific cutoff values.Results.-Overall, MC counts averaged 31 MCs per high-power field in the study group versus 24 MCs per high-power field in the control group (P , .001). When stratified by location, a significant increase was seen in biopsies from the left colon only. Receiver operating characteristic analysis revealed that overall MC counts, left-sided MC counts, and the difference between rightand left-sided MC counts did not yield discriminatory cutoff values (area under the curve, 0.68, 0.74, and 0.81, respectively).Conclusions.-Mast cell counts were increased in patients with chronic diarrhea of unknown etiology, primarily in the left colon. However, receiver operating characteristic analysis demonstrates no discriminatory cutoff values. Quantitative MC stains yield little useful diagnostic information, and further studies are necessary to determine whether mastocytic enterocolitis truly represents a distinct entity.

The role of mast cells in functional GI disorders

“…This difference in the number of MCs has been described in a variety of tissues from rodents, such as skin, myocardium and rat colon. When specifically analysed, some authors found increased MC counts in the terminal ileum, ascending and descending colon, and rectum of female versus male controls,57 60 74 with females showing 43% increase in the area occupied by MCs,7 similar to observations in patients with chronic undefined diarrhoea,53 while others do not 51 60 63. These data raise the hypothesis that gender-dependent differences in immune responses are involved in the observed higher prevalence of IBS in females, in the described gender-related differences in IBS pathophysiology and in the known effects of the menstrual cycle in the modulation of rectal sensitivity 76…”

“…This is partly due to the absence of agreement and standardisation on the methodology used to count MCs, to differences in patient and control selection, inter-individual variation, location of the biopsy, the relatively small cohort numbers for the majority of individual studies and to other uncontrolled potential confounding factors (box 1) (see Nasser et al for a detailed review). The great variation in reporting mean mucosal MC numbers in the GI tract makes the interpretation of discriminatory cut-off values very complicated and currently uninterpretable according to some pathologists 53. MC counts have been found to be normal, increased or decreased in IBS (table 2).…”

Mastocytic Enterocolits and the Role of Mast Cells in Functional and Inflammatory Intestinal Disorders: A Systematic Review

“…The largest study to date on the diagnostic significance of colonic MC involved 76 patients with chronic diarrhoea of unknown etiology (CDUE) and normal colon biopsy, and 89 asymptomatic controls [63]. The aims were to establish whether colonic MC show an increase in patients with CDUE, to determine their microscopic distribution -to see whether biopsy location is an important factorand to gain a better understanding of how MC counts might be interpreted.…”

“…This suggests that many patients could be treated empirically with MC-targeted drugs without first having to undergo an MC count. The authors therefore consider it premature to recommend MC counts as part of a routine diagnostic workup for CDUE [63].…”

Increased Mast Cell Counts and Degranulation in Microscopic Colitis

“…Mast cells had been implicated in a variety of gastrointestinal disorders including mastocytic enterocolitis, allergic mastocytic gastroenteritis and colitis, chronic diarrhea in rheumatoid arthritis, and chronic diarrhea of unknown etiology [16][17][18][19][20]. In the largest study to date on colonic mast cells, mast cell counts were found to be elevated in patients with chronic diarrhea of unknown etiology, although the mast cell count had little diagnostic utility for that particular disease [18]. In this study, we investigated whether mast cells were involved in the pathogenesis of MC, which had not been previously examined.…”