CROHN’S DISEASE HistopathologyDR AHMAD JAWAD RESIDENT GASTROENTEROLOGY

INTRODUCTION :

CD can affect different segments of the GI tract. The terminal ileum and proximal colon are the most common sites, followed by the anorectum and colon. Perianal disease varies between 14–76%.

Involvement of the upper gastrointestinal tract is uncommon.

The length of the segments involved is variable and the lesions are separated by uninvolved ‘skip areas’.

GROSS FEATURES :A distinction is made between

inflammatory disease, stricturing disease – defined as constant luminal narrowing

penetrating disease, defined by the occurrence of intra-abdominal or perianal fistulas, inflammatory masses and/or abscesses.

Fistulas are commonly associated with strictures and therefore the clinical distinction is often limited to two types : the perforating type and non-perforating type with predominantly mucosal lesions.

The mucosa may appear normal or may show multiple small (1–2 mm in size) punctiform, rounded nodules or superficial erosions known as ‘aphthoid lesions’.

Over a period of time, the erosions become confluent and give rise to larger longitudinal ulcers, known as ‘serpiginous ulcers’. The combination of longitudinal and transverse ulceration in an edematous mucosa induces a characteristic ‘cobblestone’ aspect.

Ulcerations are more common on the mesenteric border of the small intestine. They can become deeply situated fissuring ulcers reaching the muscularis propria or pass through the muscularis and give rise to abscesses or fistulas between involved segments and adjacent organs or nearby uninvolved loops.

Fistulas are often associated with strictures. Strictures are

characterized by luminal narrowing and bowel wall thickening with or without prestenotic dilatation.

In high-grade stenosis, the luminal diameter is less than 0.5 cm. They are often associated with severe ulcerations with complete circumferential loss of the mucosa.

Inflammatory pseudo polyps of the colon and small intestine (in approximately 20% of the cases), identical to those described in UC can be observed in CD. These are usually tall mucosal outgrowths measuring a few millimeters in length, but giant forms have been described.

Being a transmural disease, the bowel wall is thickened with involvement of the sub mucosa, the muscularis propria, the sub serosa and mesenteric fat.

Mesenteric fat partially surrounds the intestine, extending from the mesenteric attachment anteriorly and posteriorly corresponding to the involved segment. This phenomenon, known as ‘fat wrapping’, is specific for CD. It is observed in 75% of the surgical specimens.

Fat wrapping is defined on a transverse section of the intestine and defined as being present when more than 50% of the intestinal circumference is affected. The corresponding mesentery is usually thickened and retracted.

Endoscopic view of the interior of a patient's transverse colon (part of the large intestine) affected by Crohn's disease, showing large inflammatory polyps

Endoscopic view of the interior of a patient's colon (large intestine) affected by Crohn's disease, showing extension ulceration (white areas)

Crohn’s disease. Small intestine: fat wrapping is acharacteristic feature of Crohn’s disease. It is characterized by the overgrowth of mesenteric fat.

MICROSCOPIC FEATURESDIAGNOSTIC FEATURES

Although the degree of mimicry with UC can be high, the presence of aphthoid ulcers, fissure ulcers, transmural inflammation, fistulas, lymphangiectasia, fibrous stricturing and neural changes is predominantly a feature of CD.

It has been suggested that the diagnosis of CD should be based upon the presence of an epithelioid granuloma with one other feature suggestive or diagnostic for IBD, or the presence of three other features in the absence of granulomas.

Superficial or deep ulceration with adjacent granulation tissue extending into deep sub mucosa or below

Disease is focal with intervening normal mucosa in bowel and throughout GI tract (mouth to anus)

Goblet cells present

Initially focal neutrophils in epithelium and overlying lymphoid aggregates and plasmacytosis, then cryptitis, crypt abscesses, but usually no neutrophils in lamina propria

Mucosa and sub mucosa are also edematous

GRANULOMA : The most valuable diagnostic feature of Crohn's disease is the presence of a sarcoid or tuberculoid reaction in the affected tissue of the bowel wall.

They develop in all layers of the intestines from the mucosa to the serosa but are most frequent in the sub mucosa.

A granuloma is defined as a collection of monocyte/ macrophage cells and other inflammatory cells with or without giant cells.

The macrophages appear as large cells with abundant pale eosinophilic cytoplasm and large oval nucleus. They are arranged in clusters.

The frequency of finding granulomas in CD varies between 15% and 85%, but is rarely higher than 50–60%.

Crohn’s disease. Rectal biopsy: a granuloma, socalled because of the round appearance, is a collection ofepithelioid cells with giant cells as in the picture or without

MUCOSAL LESIONS :

Early lesions in CD include epithelial patchy necrosis, the aphthoid ulcer or mucosal micro ulcerations (loss of 1–6 cells).

Ulcers at the base of crypts with neutrophils streaming into the bowel lumen, which leads in a later phase to mountain peak ulcers, villous abnormalities and damage of small capillaries (including capillary thrombi) with subsequent loss of surface epithelial cells.

Crohn’s disease. Aphthoid ulcer in the ileum: earlymucosal ulcer, centrally located and appearing as a mountain top ulcer

Crohn’s disease. Early mucosal lesions in CD can be associated with damage of small capillaries as illustrated here bythe presence of a fibrin plug in the lumen of a small vessel

Fissuring is pathognomonic of Crohn's disease . It can be found in at least 25 % of all cases.

Fissures are particularly valuable in the diagnosis when the sarcoid reaction is absent.

Crohn's disease in surgically resected material is usually a transmural inflammation. Its features include widening of the sub mucosa by edema and inflammatory infiltrate, scattered aggregations of lymphoid tissue and certain other features which support the diagnosis although not pathognomonic.

These include thickening of the muscularis mucose, lymphangiectasia particularly of the sub mucosal lymphatics, neuromatous hyperplasia, focal arteritis and pyloric gland metaplasia of the mucosa.

Crohn’s disease. Small intestine: high-grade stenosis.The mucosa is ulcerated. Lymphoid hyperplasia is present in thedeeper parts of the bowel wall.

Transmural inflammation

Deep fissuring ulcers

Crohn’s disease is characterized by the presence of granulomas and by hyperplasia of the sub mucosal nerves, sometimes called ‘neuromatous lesion’

Crypt abscess

Crohn’s disease. Granulomatous vasculitis is anotherlesion, which is not uncommon in Crohn’s disease.

DIFFICULTIES IN THE DIAGNOSIS OF CROHN'S DISEASE

One of the principal difficulties in the diagnosis of Crohn's disease is the distinction from intestinal tuberculosis. The sarcoid reaction of Crohn's disease taken by itself can be indistinguishable from noncaseating tubercle. However, the sarcoid reaction is usually much less florid in Crohn's disease than tuberculosis.

The foci of epithelioid cells and giant cells tend to be smaller and fewer in number in CD.

Tuberculosis is an important and growing problem. Apart from tuberculosis there are no other diseases which are readily confused by the pathologist with Crohn's disease of the small intestine, although it can be misdiagnosed as malignant lymphoma.

The situation is very different in the large bowel where there is the difficult problem of the distinction between Crohn's disease and ulcerative colitis, diverticulitis and ischemic colitis.

Caseating granuloma

ULCERATIVE COLITIS OR CROHN’S DISEASE CD is characterized by transmural inflammation, whereas UC is a mucosal disease.

Segmental distribution of crypts or crypt atrophy, segmental distribution of mucin depletion, mucin preservation at the edge of an ulcer or in crypts with surrounding neutrophils, the occurrence of focal inflammation simultaneously with severe diffuse or patchy inflammation in a set of biopsies, have a significant discriminative value in favor of CD.

CD of colon resembles ulcerative colitis, but Crohn's colitis also has fistulas / sinus tracts, skip lesions, deep ulcerations, marked lymphocytic infiltration, serositis, granulomas, fewer plasma cells