The histological cut-offs for collagenous and lymphocytic colitis, incomplete microscopic colitis, the drugs that trigger it, the mimics that catch people out and two whole slide images to practise on.
- The syndrome: chronic watery, non-bloody diarrhoea with a normal or near-normal colonoscopy and diagnostic changes on biopsy.
- Collagenous colitis: subepithelial collagen band of 10 µm or more.
- Lymphocytic colitis: 20 or more surface intraepithelial lymphocytes (IELs) per 100 epithelial cells, with a normal collagen band.
- In both: crypt architecture is preserved; the lamina propria is inflamed.
- Triggers: NSAIDs, proton pump inhibitors (especially lansoprazole), SSRIs and smoking.
- Most important mimic: amyloid deposition; Congo red settles it.
What microscopic colitis is
Microscopic colitis is a chronic inflammatory condition of the colon defined by three things together: chronic watery, non-bloody diarrhoea; a colonoscopy that looks normal or nearly normal; and specific histological changes on biopsy. Because the endoscopy is usually unremarkable, the diagnosis rests entirely on the pathologist.
It mainly affects middle-aged and older adults, with a clear female predominance that is most marked in collagenous colitis. It is associated with autoimmune conditions, especially coeliac disease, thyroid disease and type 1 diabetes. Its cause is thought to be an abnormal mucosal immune response to luminal antigens in susceptible people, often set off by drugs or smoking.
Pathology MCQMicroscopic colitis is a clinicopathological diagnosis. The report should describe the findings and state that they fit microscopic colitis in the right clinical setting of chronic watery diarrhoea.
Collagenous colitis: the cut-off
The defining feature is a thickened subepithelial collagen band of 10 µm or more. The normal band is only a few micrometres thick, so the threshold is roughly one and a half red cell diameters. Measure it in a well-oriented area, because tangential sectioning makes any band look thicker.
Pathology MCQ- The band: eosinophilic, with an irregular, ragged lower border that traps capillaries and inflammatory cells.
- The surface epithelium: flattened and damaged, often detaching in strips from the collagen plate.
- The lamina propria: increased plasma cells and lymphocytes; IELs are often increased too.
- Special stains: Masson trichrome highlights the band (blue or green); Congo red excludes amyloid.
A thick-looking band in a tangentially cut biopsy, or around a lymphoid follicle, is a classic overcall. Only measure where the crypts are cut longitudinally and the surface is intact.
Lymphocytic colitis: the cut-off
Lymphocytic colitis is defined by 20 or more surface intraepithelial lymphocytes per 100 surface epithelial cells, with a collagen band that is not thickened. The normal colon has only a few IELs per 100 epithelial cells.
Pathology MCQ- Where to count: surface epithelium, not crypts, and away from lymphoid follicles, where IELs are normally increased.
- The cells: mainly CD8-positive T cells; CD3 immunostaining can help with counting but is rarely needed.
- Architecture: crypts are straight and evenly spaced; the lamina propria has a superficial lymphoplasmacytic infiltrate.
| Feature | Collagenous colitis | Lymphocytic colitis | Incomplete microscopic colitis |
|---|---|---|---|
| Collagen band | 10 µm or more | Under 10 µm (normal) | More than 5 but under 10 µm (incomplete collagenous) |
| Surface IELs | Normal or increased | 20 or more per 100 epithelial cells | More than 10 but under 20 per 100 (incomplete lymphocytic) |
| Crypt architecture | Preserved | Preserved | Preserved |
| Sex distribution | Strong female predominance | Female predominance, less marked | Variable |
| Response to budesonide | Yes | Yes | Often, in symptomatic patients |
Incomplete microscopic colitis
Some patients have the typical clinical picture but biopsies that fall just short of the thresholds. These are called incomplete (or paucicellular) microscopic colitis: a collagen band above 5 µm but under 10 µm, or IELs above 10 but under 20 per 100 epithelial cells. Many of these patients respond to the same treatment, so it is worth describing the findings rather than signing the biopsy out as normal.
Virtual slides
Work through the two diagnostic patterns side by side. Tap an annotated region and the viewer zooms straight to it.
Drug triggers
A substantial share of cases is linked to medication. The strongest associations are with NSAIDs, proton pump inhibitors and selective serotonin reuptake inhibitors, and among PPIs lansoprazole is the most often implicated. The proposed mechanism is a drug-induced change in mucosal permeability or immune response in a predisposed patient.
| Drug class | Examples | Comment |
|---|---|---|
| NSAIDs | Aspirin, ibuprofen, diclofenac | Among the most consistent associations |
| Proton pump inhibitors | Lansoprazole, omeprazole, esomeprazole | Lansoprazole carries the strongest association |
| SSRIs | Sertraline, paroxetine | Onset often within months of starting the drug |
| Others | Statins, ticlopidine, acarbose, beta-blockers | Weaker or less consistent evidence |
The classic stem is an older woman on lansoprazole and an NSAID with months of watery diarrhoea and a normal colonoscopy. The answer is random colonic biopsies, and the first step in management is stopping the culprit drug.
Mimics
The mimic that matters most is amyloid, because its pale pink subepithelial deposits can look like a collagen band on H&E.
Pathology MCQ| Mimic | What looks similar | What separates it |
|---|---|---|
| Amyloidosis | Pink amorphous subepithelial material | Deposits also involve vessel walls and deeper tissue; Congo red with apple-green birefringence |
| Ischaemic colitis | Hyalinised lamina propria | Withered crypts, diffuse hyalinisation and no surface lymphocytosis |
| Radiation colitis | Subepithelial fibrosis | Telangiectatic vessels, atypical stromal and endothelial cells, history of radiotherapy |
| Inflammatory bowel disease | Lamina propria inflammation | Crypt distortion, basal lymphoplasmacytosis and Paneth cell metaplasia in the left colon |
| Infection and drug injury | IELs and lamina propria inflammation | Neutrophilic cryptitis, apoptosis or specific features; clinical history and stool tests |
Endoscopy and biopsy protocol
The colonoscopy is usually normal. Occasionally, mostly in collagenous colitis, linear mucosal tears appear after air insufflation, the so-called cat-scratch colon, thought to reflect a less compliant mucosa.
Pathology MCQCollagenous colitis can be patchy and may spare the rectum and sigmoid. Take at least two biopsies from each of the right and left colon, in separately labelled pots; rectal biopsies alone can miss the diagnosis.
Treatment
- First step: stop or switch implicated drugs, and support smoking cessation; smokers tend to develop the disease earlier.
- Induction: oral budesonide, typically 9 mg daily for 6–8 weeks, is the most effective treatment for both subtypes.
- Relapse: common after stopping; low-dose budesonide maintenance is used for recurrent disease.
- Other options: loperamide for mild symptoms, bile acid sequestrants when bile acid diarrhoea coexists, and for refractory disease, immunomodulators or biologics (anti-TNF agents, vedolizumab) under specialist care.
Practice questions
Four quick questions on the points examiners test most, then the full question set below.
A 64-year-old woman has 4 months of watery diarrhoea. Colonoscopy is normal. Biopsies show a subepithelial collagen band measuring 14 µm with surface epithelial detachment and preserved crypts. What is the diagnosis?
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Colonic biopsies show 28 surface intraepithelial lymphocytes per 100 epithelial cells and a collagen band of 5 µm, with straight crypts. Where should the IEL count be made?
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A biopsy shows pale eosinophilic subepithelial material that also surrounds small vessels in the submucosa. Which test is most useful next?
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Which drug is most strongly associated with microscopic colitis?
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Full question set
- Collagenous colitis: collagen band 10 µm or more, measured in a well-oriented area.
- Lymphocytic colitis: 20 or more surface IELs per 100 epithelial cells, counted away from lymphoid follicles.
- Both keep normal crypt architecture; distortion points to IBD.
- Check the drug history (NSAIDs, lansoprazole, SSRIs) and do a Congo red when the subepithelial deposit looks amorphous.
- Take biopsies from both the right and left colon; budesonide is the treatment of choice.
Miehlke S, Guagnozzi D, Zabana Y, et al. European guidelines on microscopic colitis. United European Gastroenterol J 2021;9:13–37 · Nguyen GC, Smalley WE, Vege SS, Carrasco-Labra A. AGA clinical practice guideline on the medical management of microscopic colitis. Gastroenterology 2016;150:242–246 · Langner C, Aust D, Ensari A, et al. Histology of microscopic colitis: review with a practical approach for pathologists. Histopathology 2015;66:613–626 · StatPearls: Microscopic Colitis
High-Yield, Board-Style Image MCQs & Interactive Whole Slide Images
High-resolution virtual microscopy with questions aligned to ABP, FRCPath, NEET-SS, DM Hematopathology and MD/DNB.
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