Doudenum

Histopathological

diagnosis of

gluten sensitive

entropathy

Although Biopsy

Examination is gold

standard, A pathologist

doesn't make the

diagnosis,

• only can say ….

Abnormalities

are consistent with CD

Even in centers with a

high interest in CD, 12%

of Biopsy specimens are

not suitable

So the diagnosis is impossible

•Steps for better evaluation:Steps for better

evaluation:

* 4 to 5 biopsies

open cup

diameter

(4-6mm)

* Fallowing sites:

• Duodenojejunal flexure at the

level of ligamentum treitz and/or

• Distal transverse portion of

duodenvm (D3)

• Descending duodenum distal to

the papilla of vater (D2)

• Descending duodenum proximal

to the papilla of vater (D1)

• Duodenal bulb (B)

* Orient the sample

adequately on a

small piece of paper

•Embeding the specinens

on edge in paraffin wax,

for serial transverse (3-4

µm) sections and H&E

staining

Identification of four villi

in a row considered as

adequate.

Mucosal lesions: Mucosal lesions: (modified marsh classification)(modified marsh classification)

Type O: the preinfiltrative lesion (normal) Minimal mucosal changes not detectable with

conventional light microscopyType I: the infiltrative lesion (IEL, at least 40/100

entrocytes & at the top) *** In iran (upper limit of normal IEL 37/100 in HE,

39/100 in IHC)

Type II: hyperplastic (crypt elongation, budding, mitoses)

Type III (a,b,c): destructive lesion classic CD lesion(a) mild atrophy (V/c ≤ 2:1)(b) moderate atrophy (V/c ≤ 1:1)(c) sever atrophy

Type IV: flat mucosa

Immunohistochemical studies isnot part of

routine analysis,

• IHC can help in appreciating

the extent and distribution

of lymphocytic exocytosis &

CD markers

Immunostainging of Immunostainging of

IELsIELs● TCR γδ+

● 70% CD 8+

● 10% CD 4+

● 20% CD 3+

● Variable CD 103+

Histologic response to gluten free diet● varies from patient to patient● IEL and mitoses as little as one week● beginning return of villi height at least 3 months ● after 1 to 2 years on a strict diet v/c ratio may be near normal ● reappearance of histologic changes after re-exposure varies from 2 hours to 6 days.

INTESTINAL BIOPSIES

SUB-TOTAL VILLOUS

ATROPHYNORMAL MUCOSA

TGA positive TGA positiveTGA negative TGA negative

AEApositive

AEAnegative

AEApositive

AEAnegative

AEApositive

AEAnegative

AEApositive

AEAnegative

Probabilities of Biopsy and Antibodies Situations

•* Approximately 25% of patients

with CS who have also had

colonic Biopsy

lymphocytic colitis

•* 15% of patients with

lymphocytic colitis who have had

duodenal

biopsy CS

Differential

diagnosis (Abnormal

histologic patterns)

1.Entities usually associated with a diffuse severe villus abnormality and crypt hyperplasia

A. Celiac sprue

B. Refractory or unclassified sprue

C. Other protein allergies

D. Lymphocytic enterocolitis

II. Entities usually associated with a variable villus abnormality and crypt hypoplasia

A. Kwashiorkor, malnutritionB. Megaloblastic anemiaC. Radiation and

chemotherapeutic effectD. Microvillus inclusion disease

III. Entities usually associated with a nonspecific variable villus abnormality, usually not flat

A. Changes associated with dermatitis herpetiformis

B. Partially treated or clinically latent celiac sprue

C. Infection

D. Stasis

E. Tropical sprue

F. Zollinger-Ellison syndrome

G. Mastocytosis

H. Nonspecific duodenitis

I. Autoimmune enteropathy

J. Torkelson syndrome

IV. Entities associated with variable villus abnormalities

illustrating specific diagnostic changes

A. Common variable immunodeficiency

B. Whipple’s disease

C. Mycobacterium avium-intracellulare complex infection

D. Eosinophilic gastroenteritis

E. Intestinal lymphoma

F. Parasitic infestation

G. Waldenstrom’s macroglobulinemia

H. Lymphangiectasia

I. Enteropathy-associated T-cell lymphoma

Potential pitfals:Potential pitfals:● Tangenitally cut sections

● Superficial biopsies inthout muscularis mucosa

● Villi adjacent to lymphoid follicles

* Any evidence of brunner’s glands, gastric metaplasia, duodernitis

Sample should be disregarded and repeated

more distally.