B. Assessment of crypt density, architecture and epithelium :

   Dr  Sampurna Roy  MD

1. Crypt density:

The biopsy should be well-oriented with muscularis mucosae included and should be assessed along the entire length. Lymphoid follicles should be avoided.

Normally there are 7 to 8 closely packed crypts per millimeter  length of muscularis mucosae (Normal histology: click) . 

 In chronic inflammatory bowel disease there are about 4 to 5 crypts per mm so that  the  intercryptal space is equivalent to or greater than the crypt diameter.

Note: There is increase in the intercryptal space in normal caecal and distal rectal mucosa and should not be confused with chronic idiopathic inflammatory bowel disease.

 2. Crypt architecture:   Distortion, branching, atrophy, degeneration, serration, dilatation and misplaced crypts:

(Fig A) - Crypt distortion - characterized by non-parallel crypts of variable diameter. After severe damage the crypts may run parallel to the surface.

Crypt branching or bifurcation indicates growth or regeneration after injury.

Criteria for assessment of abnormality - (i) Biopsy should be well oriented   (ii) Include at least 2 mm length of muscularis mucosae (iii) Should contain more than two branched crypts.

Crypt irregularity is present in -(i) Ulcerative colitis (ii) Following re-epithelialization and healing of ischaemic ulceration (iii) In normal biopsy due cross cutting of crypts.

Crypt alignment is usually maintained in  (i) Crohn's disease  (ii) Infective colitis.

(Fig B) - Crypt atrophy or shortening is characterized by reduction of number of crypt and increased distance between crypt bases and muscularis mucosae.

Paneth cells may be present in shortened crypts in chronic cases.

Crypt atrophy is present in -(i) chronic ulcerative colitis (ii) healed ischaemic colitis (iii) radiation colitis  (iv) graft versus host disease.

Biopsy mimicking features of crypt atrophy- (i)Uniform shortening due to tangential cutting (ii)Biopsy from normal caecum, distal rectum and from mucosa close to anal margin (iii)Thickening of the lamina propria due to oedema.

(Fig C & Fig D)- Crypt degeneration of the superficial half of the crypts occur in ischaemia and pseudomembranous colitis.

Degenerative changes throughout the full length of the crypts occur in ischaemic colitis or infective proctocolitis.

 ['Withered' crypts are present in infective colitis and are characterized by thin crypts,uneven lumen and pointed crypt base. The crypt cells appear small and pyknotic and there is mucin depletion].

(Fig E) - Multifocal crypt necrosis is present in graft versus host disease.

Crypts have a 'moth-eaten appearance'.

Necrotic crypt epithelial cells are surrounded by plasma cells and lymphocytes.

(Fig F) - Crypt serration is present in metaplastic/hyperplastic polyp.

(Fig G) - Crypt dilatation with some polymorphs within the crypt may be due to obstruction of mouth of a crypt.

Further deeper sections should be examined.

Groups of dilated crypts with inflammatory debris may be present in a case of pseudomembranous colitis.

Cystic dilatation may be present in polypoid lesions (eg. Juvenile polyp, Cronkhite-Canada syndrome). (Visit: Juvenile polyp ; Peutz-Jeghers polyp ; Inflammatory fibroid polyp ; Multiple Lymphomatous polyposis ;  Lymphoid polyp )

(Fig H) - Misplaced crypts are characterized by crypt epithelium below the muscularis mucosae. This may be present in the following conditions:

(i) Solitary ulcer of the rectum  (ii) Mucosal damage due to ischaemic infarction or torsion. (iii) Colitis cystica profunda  (iv) Lymphoid glandular complexes.

3. Crypt epithelium :  Mucin depletion, regenerative hyperplasia, dysplastic epithelium, neutrophil polymorph infiltration (cryptitis & crypt abscess).

(Fig I) - Mucin depletion - Diffuse loss of goblet cells (graded as mild, moderate or severe) occurs in ulcerative colitis , ischaemic, infective and radiation colitis.

In Crohn's disease it is less prominent and focal in nature.

(Fig J) - Regenerative hyperplasia is characterized by increase in undifferentiated crypt base cells.

The nuclei of the cells are large and hyperchromatic.

Mitotic figures are present high up in the crypt epithelium, away from the crypt base.

Regenerative hyperplasia is noted in active ulcerative colitis and following any ulcerative process.

These changes should not be mistaken for dysplasia of the epithelium.

(Fig K)- Dysplasia of the epithelium (low of high grade) characterized by cytological and architectural atypia.

There is nuclear enlargement, hyperchromatism, pleomorphism, nuclear stratification, loss of polarity and no evidence of maturation towards the mucosal surface.

'Dystrophic' goblet cells (enlarged, rounded off with eccentric nuclei) are present.

(Fig L) - Crypt abscess - Neutrophil polymorphs in the lumen may distend or disrupt the crypts.

Polymorphs may be graded on numbers per crypt.

Presence of more than 10 neutrophils in more than two crypts in any one biopsy is indicative of active inflammation.

Crypt abscesses are common in ulcerative colitis but are not diagnostic of it.

Cryptitis - Neutrophils are present between crypt epithelial cells.

Presence of cryptitis as a predominant feature in a biopsy is indicative of an infective colitis.

(Fig M) - Paneth cells are normally present in the caecum. In chronic ulcerative colitis these are present at the base. the crypts in the rectum and colon.
Visit: Interpretation of Large Intestinal Biopsies : click

Assessment of the Intestinal abnormalities - lumen, surface epithelium and the subepithelial  zone : click

Assessment of abnormalities :changes in the lamina propria,muscularis mucosae and submucosa ): click