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Assessment of Abnormalities of Large Intestinal Biopsies -3  

C.  Changes in the lamina propria, muscularis mucosae and submucosa



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1. Changes in the lamina propria :

(Normal histology)

I. Changes in Cellularity :

- Patterns of cellularity:

A.  Diffuse:  Diffuse superficial : Cellular infiltrate confined to the superficial and middle third of lamina propria (eg. Infective colitis).

Diffuse transmucosal : Increase in cellular infiltrate throughout the lamina propria- (Example: Ulcerative colitis).

B. Discontinuous: Focal increase in inflammatory cells in a background of normal mucosa (Example: Crohn's disease).

Patchy inflammation characterized by variation in intensity of inflammation from one part of mucosa to another  (Example. Tuberculosis ; Amoebiasis ; foreign body reaction and wide variety of other conditions).

- Inflammatory cellular component:

Increase in neutrophils  in the lamina propria is an important marker of active inflammation. Polymorph inflammation may be graded on numbers per crypt or per millimeter in lamina propria.

In florid acute inflammation neutrophil polymorphs are present in large numbers in the lamina propria, within epithelium and in the lumen of crypts forming crypt abscess. (Example: Active phases of ulcerative colitis, Amoebiasis, acute infective proctocolitis).

Plasma cells are non-specific marker of inflammation.

A heavy infiltrate of plasma cells may predominate throughout the lamina propria in case of chronic ulcerative colitis. 

Lymphocytes are of diagnostic significans when present in large numbers.

In follicular proctitis there is hyperplasia of lymphoid follicles in the lamina propria  (Example: Ulcerative colitis).

Irregularly arranged dense aggregates of lymphocytes adjacent to bases of crypts with extension into the submucosa is seen in Crohn's disease.

Lymphoma should be ruled out when there is an increase in intraepithelial lymphocytes.

Eosinophils may be present in a wide range of conditions.

(Example: Early schistosomiasis ; some cases of ulcerative colitis; as systemic reaction  in atopic disease like asthma ; in acute phase of irradiation proctitis etc.)   

PAS positive histiocytes are noted in whipple's disease ; melanosis coli; malakoplakia ; histoplasmosis etc. 

In xanthoma lipid containing histiocytes are present in the superficial lamina propria.

Brown pigment containing macrophages are present in melanosis coli.

Granulomas and giant cells: A granuloma consists of at least five epithelioid cells with or without accompanying multinucleated giant cells.

This is a specific marker of Crohn's disease (a submucosal granuloma is diagnostic).  

Well formed granulomas are identified in the following disease conditions:

1. Crohn's  

2. Tuberculosis 

3. Sarcoidosis

4. Mycobacterium avium intracellular infection in patients with AIDS.

5. Around ova in chronic  schistosomiasis.

6. Fungal infection

7. Foreign body reaction

8. Diversion colitis. Giant cells may be present in response to crypt destruction or in response to foreign material (faecal material or barium).

Pericryptal histiocytic reaction in response to crypt rupture may be present in infective colitis or ulcerative colitis. Crohn's should not be diagnosed based only on the presence of giant cells or ill defined collection of histiocytes.

Other changes in the lamina propria:

Pseudolipomatosis of the large intestinal mucosa is characterized by small gas containing vacuoles in the lamina propria resembling mature adipose tissue.

The vacuoles probably appear following prolonged lymphocytic infiltration.

(Example: Longstanding ulcerative colitis)

Microorganisms may be present in the lamina propria and these include amoebae , cryptosporidia, schistosomal ova , actinomycosis , cytomegalovirus and herpes simplex .

II. Changes in the matrix of the lamina propria:

a) Fibrosis of lamina propria :

(i) Solitary ulcer syndrome.

(ii) Dysplastic glandular epithelium in a desmoplastic stroma is highly indicative of adenocarcinoma.

b) Presence of muscle fibres in the lamina propria:

(i) Solitary ulcer syndrome (mucosal prolapse)

(ii) Polyps- eg. Inflammatory 'cap' polyp and Peutz Jegher's polyp.

c) Hyalinization of the lamina propria : In chronic radiation damage.

d) Haemorrhage in the lamina propria : 

(i) could be an artefact.

(ii) Useful sign in acute ischaemic colitis.

2. Changes in the muscularis mucosae and submucosa:

 I  Muscularis mucosae -

Expansion, stricture formation, fibrosis, splaying of fibres :

Thickening of muscularis mucosae occurs near an obstructive lesion (Example: Carcinoma or Hirschsprung's disease) and in chronic ulcerative colitis.

A  non-malignant stricture (common complication of Crohn's disease) is histologically characterized by an increase in smooth muscle cells in the muscularis mucosae and presence of large amounts of collagen (Type V and III ), laminin and tenasin.     

Splaying of muscle fibres into the lamina propria is noted in 'mucosal prolapse syndrome'.

 II  Submucosa -

Edema - Widening of submucosa by edema is a sign of active disease (eg. Crohn's disease).

Inflammation - Numerous lymphoid aggregates and nodules are present in the submucosa in Crohn's disease. 

Disproportionate inflammation is characterized by inflammatory infiltrate in the submucosa which is denser than the inflammation in the overlying mucosa (Example: Crohn's).

Inflammation in the submucosa with almost normal mucosa may be present adjacent to a diverticulum or abscess, in a deep flask-shaped ulcer of amoebiasis, at the edge of a fissure and in tuberculosis. 

Nerve - Irregular hypertrophy and hyperplasia of the nerve fibres (neuromatous lesions) and unusually prominent submucosal nerve ganglia may be present Crohn's disease. 

Vascular lesions - Inflammatory cell infiltration of blood vessels and obliterative lesions have been noted in the submucosa in Crohn's disease. 

Granulomatous vasculitis and lymphangiectasia in the submucosa are common findings in Crohn's disease.  

Rectal biopsy is an useful diagnostic tool in the detection of systemic vasculitis and amyloid. 

Blood vessels in the submucosa should also be examined in suspected cases of angiodysplasia.

Misplaced glands are distinguished from carcinoma by the presence of lamina propria around the glands  together with  haemosiderin laden macrophages.

Interpretation of Large Intestinal Biopsies

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

Assessment of the Intestinal abnormalities :crypt density, architecture and epithelium


Further reading:

(1) Non-neoplastic intestinal disease. In Sternberg SS(ed). Diagnostic Surgical Pathology.3rd ed. Philadelphia,Lippincott, Williams & Wilkins,1999 ; 1344-1411. 

(2) Assessment of abnormalities : Diagnostic signposts. In biopsy pathology in colorectal disease.London: Chapman and Hall,1987; 261-2.  

(3) Observer variability in the histopathological reporting of abnormal rectal biopsy specimens. J Clin Pathol. 1994 ;47:48-52.

(4) Interpretation of large intestinal mucosal biopsy specimens. Hum Pathol 1994; 25: 1150-9


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Consultant  Histopathologist (Kolkata - India)






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