Biopsy Diagnosis of Celiac Disease

Overview

The features in a duodenal biopsy suggesting celiac disease include an intraepithelial lymphocytosis, villous atrophy, crypt hypertrophy, abnormal epithelial cells and increased chronic inflammatory cells in the lamina propria. Other features that may be present include gastric metaplasia. Jejunal biopsies are not necessary for the diagnosis of celiac disease, duodenal biopsies are sufficient.


Figure 1
  
The normal small intestinal or duodenal biopsy (FIGURE 1) consists of long finger like villi and small crypts, forming a crypt to villous ratio of 1 to 3 or 4. The epithelial cells have basal nuclei and a normal surface microvillous structure.


Figure 2		  


There is a spectrum of pathologic changes that ranges from normal architecture with intraepithelial lymphocytosis (FIGURE 2).

Normally there should be fewer than 30 lymphocytes per 100 epithelial cells. This change is followed by the development of crypt hyperplasia.

     

Figure 3

  
Figure 4
Partial villous atrophy (FIGURE 3), subtotal villous atrophy and total villous atrophy are the subsequent changes. This final highpower view of a villous tip demonstrates marked intraepithelial lymphocytosis (FIGURE 4).
     

Follow-up biopsy

These changes are reversible, returning to normal on a gluten-free diet. Return to normal is considered the norm in children [16]. In adults, however, the biopsy appearance frequently does not normalize [17].

Pitfalls in the biopsy diagnosis of celiac disease

These include: 1. Inadequate number of biopsy pieces. The disease is patchy, this combined with the fact that all biopsy pieces may not be oriented sufficiently to assess the crypt to villous ratio means that at least 4 to 6 biopsy pieces need to be taken. Biopsy of the descending duodenum is sufficient. 2. Over-interpretation of villous atrophy because of poor orientation of the biopsies. If the pieces are not sufficiently oriented to assess the presence of, or degree of villous atrophy deeper cuts of the tissue block need to be ordered. 3. If the biopsy interpretation does not match either the clinical impression or serologic results the biopsy should be re-interpreted by a pathologist expert in the interpretation of gastrointestinal pathology.

Causes of villous atrophy apart from celiac disease

In children less than two years old, there are several causes that include cows milk allergy, soy allergy, eosinophillic gastroenteritis, and viral gastroenteritis. In adults, HIV enteropathy and tropical sprue are the most common causes of villous atrophy apart from celiac disease. Radiation may cause a similar picture as well as autoimmune enteropathy. Other food intolerances have been reported though are exceptionally rare; they include a single case report of fish and chicken intolerance [18].