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Biopsy Diagnosis of Celiac Disease: The Pathologist's Perspective in Light of Recent Advances. Celiac disease is a common immune-mediated disorder that occurs in individuals with permissive genetics (HLA-DQ2/DQ8 genotype) following exposure to certain wheat proteins. The histopathologic manifestations of small intestinal mucosal injury (villus atrophy, crypt hyperplasia, and intraepithelial lymphocytosis) are well recognized. However, these findings are not specific for celiac disease, because they are observed in other small intestinal disorders. These mimics include common and rare entities, the list of which continues to grow. This article discusses the histopathology and differential diagnosis of celiac disease and provides the pathologist's perspective on biopsy adequacy, evaluation, and reporting in light of current knowledge.