crohn's disease histopathology

1. CROHN’S DISEASE
Histopathology
DR AHMAD JAWAD
RESIDENT GASTROENTEROLOGY

2. 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’.

3. 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.

4.  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.

5.  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.

6.  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.

7. 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

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

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

11. MICROSCOPIC FEATURES
DIAGNOSTIC 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.

12.  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

13. 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%.

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

16. 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.

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

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

19.  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.

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

21. Transmural inflammation

22. Deep fissuring ulcers

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

25. Crypt abscess

26. Crohn’s disease. Granulomatous vasculitis is another
lesion, which is not uncommon in Crohn’s disease.

27. 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.

28.  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.

29. Caseating granuloma

30. 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