Tricks of the trade: How to avoid histological pitfalls in celiac disease

Currently, the diagnosis of celiac disease (CD) is based upon the combination of raised serum anti-tissue transglutaminase or anti-endomysial antibodies and the presence of histological alterations of variable degree in the duodenal mucosa. Interpretation of duodenal biopsies is subjected to a number of variables, and the lack of standardization may cause diagnostic controversy or even misdiagnosis. The aim of this overview is to solicit a standardization of the procedures of biopsy taking, orientation, processing, staining and interpretation in order to avoid or minimize misinterpretation of duodenal biopsies. Based on a literature review and extensive personal experience, the appropriate methodology of duodenal biopsy taking, orientation, fixation, processing, staining and interpretation was thoroughly reviewed, and the most common and relevant errors and artifacts were identified. To maximize the diagnostic yield of duodenal biopsy in CD, multiple specimens are best taken from different sites of the duodenum during endoscopy, and careful visual inspection of the duodenal mucosa may help identify abnormalities related to villous atrophy. Biopsy handling and orientation are of utmost importance to avoid artifacts that may impair the pathologist's ability to detect pathology and normality. Immunostaining with anti-CD3 monoclonal antibody should be carried out, and a simplified histological classification may help distinguish atrophic from non-atrophic stages of CD enteropathy. Meticulous attention to biopsy orientation, handling and processing - together with the knowledge of the most common histological artifacts - is necessary to avoid a wrong histological interpretation which, in turn, may lead to misdiagnosis in CD.