Scot M. Lewey, DO, FACG, FASGE, AGAF
Clinical Professor of Medicine
The diagnosis of celiac disease is confirmed by a characteristic abnormal appearance of the small intestine under the microscope. Flattening of the normal finger like projections called villi accompanied by signs of inflammation is taken to indicate damage or injury from the storage protein gluten in wheat and similar proteins in barley and rye. The small intestine biopsy became the gold standard for the establishing the diagnosis of Celiac disease or gluten sensitive enteropathy though before 1960 gluten withdrawal followed by improvement and subsequent worsening upon rechallenge was the diagnostic criteria.
Early in 1960’s through the 1970’s the small intestine was biopsied by having people swallow a small metal capsule that was attached to a suction tube that used to suction up tissue into the capsule before guillotining off some tissue once the capsule was confirmed to be in the small intestine by x-ray. Now the tissue is now obtained by upper endoscopy, the passage of a lighted video scope through the mouth under sedation to the small intestine where biopsies are obtained with cupped forceps.
Celiac disease biopsy: What does the pathologist look for under the microscope?
The small intestine normally has finger like projections called villi that give it a large surface area or contact area for food. The villi result in a shag carpet or terry cloth towel type appearance. Lining the outside surface of each villous are intestinal cells or enterocytes that secrete mucus, absorb fluids, nutrients minerals like iron, and vitamins like B12. On the surface of the enterocytes are digestive enzymes like lactase that digests lactose or milk sugar. At the base of the villi are crypts or circular like collections of intestinal cells.Celiac disease biopsy: What is villous atrophy?
Normally, villi are 3-5 times longer than the crypts are tall. However, intestinal injury can result in blunting, shortening (partial villous atrophy) or complete loss of the villi and flattening (villous atrophy) of the intestinal surface. The shag carpet will have bare spots or the terrry cloth towel robe or towel becomes like a tee shirt. The result is lack of absorption of nutrients and water resulting in weight loss, malnutrition, and diarrhea.
·Lymphocytes are a type of white blood cell important in immune function. The typically appear as purplish circles on standard H&E type stain of intestinal tissue obtained from biopsy.
· Specialized lymphocytes are present in the intestine lining.
· The intestinal lining cells are called enterocytes and are a type of epithelial cell.
· The intestinal lining is an epithelial lining.
· Lymphocytes that are activated and migrated up from crypts at the base of the intestine villi to the tip are called intra-epithelial lymphocytes.
· Normally, there are much fewer than 25-30 lymphocytes per 100 enterocytes in each villous or < 9 per villous tip.
· For thirty years, more than 40 IEL’s/100 enterocytes was considered abnormal and diagnostic of Celiac in the context of appropriate history and abnormal celiac blood tests. It is the number still used by many pathologists.
· More recently, 30 intra-epithelial lymphocytes per 100 enterocytes (6 or more IEL’s per 20 enterocytes) became the accepted criteria for intra-epithelial lymphocytosis and diagnosis of Celiac disease when villous blunting or atrophy are absent but blood tests are positive.
· IEL’s are easier to see and count with special immune chemistry stains.
· See the special stain photograph above showing increase IEL’s in a villous tip in Celiac disease. The IEL’s are brownish red with this particular stain whereas normal intestinal cell nuclei are purplish.
· Sometimes this stain is necessary to determine IEL’s from normal intestinal nuclei and better determine the number, especially if someone has already restricted gluten in their diet.Studies have shown that apparently normal appearing small intestine biopsies when stained with special stains for IEL’s reveal abnormal numbers as the earliest sign of gluten injury, especially in high risk individuals like family members of people with Celiac disease