GI Tract - Dig

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  Homme de 50 ans se plaignant de diarrhée chronique. Examen clinique, endoscopique et imagerie normaux.   50 yo male complaining of chronic diarrhea. Physical, endoscopic and X Ray exams normal.  
  Biopsies endoscopiques coliques   Endoscopic colonic biopsies  
  CD3   CD3  
  CD3   CD3  
  CD3   CD3  

Diagnostic proposé








Colite lymphocytaire


Proposed diagnosis








Lymphocytic colitis

  Ref Rosai and Ackerman’s Surgical Pathology (10th Ed.)  

Lymphocytic (microscopic) colitis appears to be closely related to collagenous colitis. There are occasional transitions between these two disorders, which have been grouped by some under the term ‘watery diarrhea–colitis syndrome. The main microscopic differences between the two conditions are the absence of a thickened collagenous layer and the greater prominence of intraepithelial lymphocytes in lymphocytic colitis. Changes morphologically indistinguishable from lymphocytic colitis have been consistently found in large bowel biopsies of patients with celiac disease, further suggesting a pathogenetic relationship between these two disorders.
The terminal ileum may be involved in cases of collagenous or lymphocytic colitis. Recently, a subtype of lymphocytic (microscopic) colitis containing scattered multinucleated giant cells in the subepithelial region has been described.
It is still unclear whether lymphocytic colitis is a specific entity or not. It has been suggested that it represents a heterogeneous group as far as etiology is concerned. In some instances, the microscopic features of lymphocytic colitis have been seen in patients later found to have Crohn disease. The matter is complicated by the fact that in some cases of collagenous/lymphocytic colitis there may be crypt irregularities, neutrophilic cryptitis, and crypt abscesses. Finally, it should be mentioned that colonic biopsies taken in patients with Brainerd diarrhea (a chronic watery diarrhea of unknown etiology characterized by acute onset and prolonged duration) show a microscopic appearance similar to that of lymphocytic colitis but usually lacking surface degenerative changes.


Eric Goosenberg, MD; Chief Editor: Julian Katz, MD


Collagenous colitis (CC) was described concurrently in 1976 by Lindstrom and by Freeman. In 1980, Read described microscopic colitis, which is clinically indistinguishable from CC but is differentiated from it by colonic biopsy features. Later, the term lymphocytic colitis (LC) was proposed by Lazenby to replace the term microscopic colitis and to distinguish it from infectious colitis and inflammatory bowel disease (ulcerative colitis and Crohn disease). The term microscopic colitis is now used to describe both CC and LC, and these conditions should be considered in any patient with unexplained nonbloody diarrhea. Patients undergoing either sigmoidoscopy or colonoscopy for unexplained diarrhea who have normal endoscopic findings should have biopsy samples taken to diagnose or rule out either form of microscopic colitis.
LC and CC are relatively rare conditions that are diagnosed when a patient with chronic watery nonbloody diarrhea has an endoscopically or radiographically normal colon, but colonic biopsies show unique inflammatory changes. Because the mucosa is not ulcerated or otherwise disrupted, the diarrhea generally does not contain blood or pus.

The characteristic feature of LC is an infiltration of lymphocytes into the colonic epithelium. CC shares this feature but additionally shows a distinctive thickening of the subepithelial collagen table. LC and CC have been suggested to represent different phases of a single pathophysiologic process, with LC possibly being a precursor or earlier phase of CC; however, this has not been proven.
The diarrhea in CC is more likely due to the inflammatory process than to the subepithelial collagen layer, although this layer may serve as a cofactor in the role of a diffusion barrier.
Increased levels of immunoreactive prostaglandin E2 in stool water may contribute to a secretory diarrhea.
Some patients with CC and concurrent collagenous infiltration of the duodenum and/or the ileum have demonstrated altered small bowel dysfunction, demonstrated by reduced D-xylose absorption.
Some individuals have bile acid malabsorption demonstrated by the Se-75-homotaurocholate (SeHCAT) test, in which a positive test result is shown by retention of less than 11% of the administered dose of radioactivity after 7 days.
Some patients with CC may have increased mucosal secretion of vascular endothelial growth factor, a fibrosis-enhancing peptide.


Histological Findings
Surface epithelium shows a chronic inflammatory infiltrate of plasma cells, lymphocytes, and eosinophils in the lamina propria.
Intraepithelial lymphocytosis, with greater than 20 lymphocytes per 100 epithelial cells, is pathognomonic of the diagnosis of LC, although lesser numbers of IEL may be present in some patients with LC.Lymphocytic colitis (LC) showing marked chronic inflammatory cell infiltrate of the surface epithelium with preservation of crypt architecture. Subepithelial collagen layer is not thickened.
Epithelial cell damage is demonstrated by cell flattening, subepithelial blebs, and denuded epithelium. Fixed specimens may show epithelial loss and detachment.
Crypts may have minimal architectural distortion as in Crohn's disease or ulcerative colitis. However, typically, evenly spaced parallel crypts of equal diameter are present.
CC shares the histologic features of LC but additionally demonstrates a thickened subepithelial collagen layer (usually >10 µm) in the lamina propria, compared to a normal thickness of 5-7 µm.
For comparison, a representative biopsy of CC is shown in the following image. Collagenous colitis (CC) showing similar inflammatory cell infiltration as in lymphocytic colitis (LC), with the characteristically thickened subepithelial collagen layer.
In some biopsy specimens, the surface epithelium may be denuded or partially detached from the collagen layer, even simulating pseudomembranes in rare cases. This either may be artifactual or may be due to a defect in adherence to the subepithelial membrane.


Approximately 20% of patients may have a spontaneous remission without specific therapy.
More than half of patients treated for LC experienced resolution of symptoms after 6 months of treatment, while only 15% of patients had significant persistent symptoms.
In some patients, the diarrhea may wax and wane over many years; however, more than 80% of patients can expect diarrhea and histologic abnormalities to resolve within 3 years.
Rare cases with severe and protracted diarrhea have been fatal; these cases are likely thought to be due to epithelial membrane sloughing and resultant altered mucosal permeability.
Although some small studies have suggested otherwise, microscopic colitis (either CC or LC) does not appear to increase the risk of colon cancer.

  Microscopic colitis as a missed cause of chronic diarrhea
Nooroudien Mohamed, Monique Marais, and Juanita Bezuidenhout

World J Gastroenterol. 2011 April 21; 17(15)



AIM: To determine the prevalence of increased intraepithelial lymphocytes, using immunohistochemistry in patients with normal colonoscopy and near normal biopsy.
METHODS: We retrospectively reviewed all non-malignant colon mucosal biopsies between 2005 and 2007, reported as normal, chronic inflammation or melanosis coli in patients who were undergoing routine colonoscopy. Immunohistochemistry using CD3 was performed on all mucosal biopsies and an intraepithelial lymphocyte count (IEL) was determined. Cases with an IEL count of ≥ 20 IELs per 100 surface epithelial cells were correlated with demographic, clinical and follow-up data. A further subgroup was evaluated for lymphocytic colitis.
RESULTS: Twenty (8.3%) of 241 cases revealed an IEL count ≥ 20. Six (2.5%) patients were identified as having lymphocytic colitis (P < 0.001), of whom, five were missed on initial evaluation (P = 0.01). Four of these five patients were labeled with diarrhea-predominant irritable bowel syndrome (IBS). On follow-up, three of the remaining 20 cases were diagnosed with malignancy (renal cell carcinoma and myelodysplastic syndrome) and one had an unknown primary tumor with multiple liver metastases. Two cases of collagenous colitis with an IEL count < 10 were included in this study. Increased IELs were not confined to patients with diarrhea as a primary presenting symptom, but were also present in patients with abdominal pain (n = 7), constipation (n = 3) and loss of weight (n = 1).

CONCLUSION: Immunohistochemistry using CD3 is of value in identifying and quantifying IELs for the presence of microscopic colitis in patients with diarrhea-predominant IBS.