Subtitle: How to tell intestinal tuberculosis from Crohn’s disease on endoscopy, imaging, biopsy and resection: granuloma size, caseation and confluence, ulcer patterns, AFB and GeneXpert, the ATT trial, virtual slides and 10 case-based MCQs.

Author: PathologyMCQ Editorial Board

Category: GI Pathology / Infectious Pathology

Last Updated: October 2026

Read Time: 10 minutes

At-a-Glance

• Why it matters: intestinal tuberculosis (ITB) needs anti-tubercular therapy (ATT); Crohn’s disease (CD) needs immunosuppression, which can make undiagnosed TB disseminate.
• Strongest pointers to TB: caseation, large confluent granulomas, ulcers lined by epithelioid histiocytes, necrotic mesenteric nodes, AFB or a positive GeneXpert.
• Pointers to Crohn’s: few small discrete granulomas, chronic architectural distortion away from granulomas, longitudinal ulcers, skip lesions, perianal disease, creeping fat.
• Reality: no single feature is decisive. Combine endoscopy, imaging, histology and microbiology; when doubt remains in an endemic area, consider an ATT trial.

Why the Distinction Matters

Both diseases favour the ileocaecal region and present with pain, diarrhoea, weight loss and fever. They are especially hard to separate in South and South-East Asia, where TB is common and Crohn’s disease is rising.

• Missed TB: steroids or anti-TNF drugs can cause disseminated, life-threatening tuberculosis.
• Missed Crohn’s: months of unnecessary ATT delay effective treatment and expose the patient to drug toxicity.
• Overlap: both can be granulomatous, transmural, stricturing and ileocaecal.

Key Discriminating Features

Weigh the evidenceWhich way does the balance tip?

Biopsy · favours TBBig, confluent, caseatingLarge granulomasOften over 200 to 400 µm, many per biopsy, confluent, submucosal

Biopsy · favours TBHistiocyte-lined ulcersSubmucosa > mucosaUlcers lined by epithelioid histiocytes; disproportionate submucosal inflammation

Biopsy · favours CDSmall, sparse, discreteMicrogranulomasFew, non-caseating, away from crypts

Biopsy · favours CDChronic distortionAway from granulomasCrypt distortion and basal plasmacytosis in uninvolved-looking mucosa

Rule of thumb: caseation is the most specific sign of TB, but it is absent in most biopsies. Absence of caseation or AFB never excludes tuberculosis.

Endoscopy and Gross Features

Gross pathology · side by sideIntestinal tuberculosis vs Crohn’s disease

Intestinal tuberculosis

Transverse ulcersUlcers run around the bowel circumference, often with undermined edges.

Serosal tuberclesSmall grey-white nodules on the serosa over the affected segment.

Inflammatory thickeningThick, rigid ileocaecal wall that narrows the lumen into short strictures.

Crohn’s disease

Creeping fatMesenteric fat wraps around the serosal surface of the bowel.

Deep fissuring ulcersKnife-like fissures penetrate the wall and can form fistulae.

Cobblestone mucosaLongitudinal and transverse ulcers isolate islands of oedematous mucosa.

Remember: strictures, wall thickening and an ileocaecal mass occur in both. Gross features guide sampling; histology and microbiology make the call.

• TB: transverse ulcers with undermined edges, small serosal tubercles, a gaping (patulous) ileocaecal valve, and short hourglass strictures.
• Crohn’s: longitudinal and aphthous ulcers, cobblestoning, skip lesions, fat wrapping, fistulae and long strictures.
• Both: wall thickening, strictures and an ileocaecal mass can occur in either; fibrosis is prominent in both.

Histology on Biopsy

Histology · side by sideGranulomas: TB vs Crohn’s

Intestinal tuberculosis

• Large granulomas, often over 200 to 400 µm
• Caseous necrosis (most specific, but often absent)
• Confluent and numerous, often in the submucosa
• Ulcers lined by a band of epithelioid histiocytes

Crohn’s disease

• Small, ill-formed microgranulomas
• Few, discrete and non-caseating
• Lie away from damaged crypts; granulomas around ruptured crypts are non-specific
• Chronic architectural distortion and basal plasmacytosis

Remember: no single histological feature is decisive. Weigh the whole biopsy with endoscopy, imaging and microbiology.

• Take enough tissue: multiple biopsies from ulcer edges and the ileocaecal valve raise the yield of granulomas and caseation.
• Count and measure granulomas: large (over about 200 to 400 µm), numerous and confluent granulomas favour TB.
• Ignore crypt-associated granulomas: granulomas around ruptured crypts are non-specific and also occur in ulcerative colitis and infections.
• Look away from the granulomas: chronic architectural distortion and basal plasmacytosis in other fragments favour Crohn’s.
• Transmural features belong to resections: transmural lymphoid aggregates and fissures favour Crohn’s; caseating nodal granulomas favour TB.

Virtual Slides

Compare ileal tuberculosis with a Crohn’s granuloma, then try the practice slide using the checklist. Where a slide has annotated regions, tap one to zoom straight to it.

Ancillary Tests

A Practical Approach

• 1. Biopsy well: several samples from ulcers and the ileocaecal valve; send one fresh for GeneXpert and culture.
• 2. Read the granulomas: size, number, confluence, caseation, location and ulcer lining.
• 3. Look beyond the granulomas: chronic architectural distortion elsewhere favours Crohn’s.
• 4. Integrate: combine endoscopy, CT, chest imaging and microbiology. Report histology as favouring one diagnosis rather than overcalling.
• 5. If still uncertain in an endemic setting: an empirical ATT trial with reassessment of clinical response (about 2 months) and endoscopic healing helps; no response suggests Crohn’s.
• 6. Before immunosuppression: always exclude active TB and screen for latent TB before steroids or anti-TNF therapy.

Test Yourself: 10 MCQs

Exam Pearls

• Caseation is the most specific feature of TB but is seen in only a minority of biopsies.
• Large, confluent, numerous, submucosal granulomas and ulcers lined by epithelioid histiocytes favour TB.
• Crypt-associated granulomas are non-specific; do not use them to diagnose Crohn’s.
• Transverse ulcers and a patulous ileocaecal valve favour TB; longitudinal ulcers, cobblestoning and perianal disease favour Crohn’s.
• Necrotic mesenteric nodes on CT favour TB; comb sign and creeping fat favour Crohn’s.
• Negative AFB or GeneXpert does not exclude TB.
• Exclude TB before steroids or anti-TNF therapy.

Video lesson

ITB vs Crohn’s, explained

The key gross, endoscopic and microscopic differences in one video.

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References

• Kirsch R, Pentecost M, Hall PM, et al. Role of colonoscopic biopsy in distinguishing between Crohn’s disease and intestinal tuberculosis. J Clin Pathol. 2006;59:840–844.
• Pulimood AB, Ramakrishna BS, Kurian G, et al. Endoscopic mucosal biopsies are useful in distinguishing granulomatous colitis due to Crohn’s disease from tuberculosis. Gut. 1999;45:537–541.
• Makharia GK, Srivastava S, Das P, et al. Clinical, endoscopic, and histological differentiations between Crohn’s disease and intestinal tuberculosis. Am J Gastroenterol. 2010;105:642–651.
• Kedia S, Das P, Madhusudhan KS, et al. Differentiating Crohn’s disease from intestinal tuberculosis. World J Gastroenterol. 2019;25:418–432.