Is PAS Stain Necessary to Exclude Whipple Disease in Duodenal Biopsies?

Objective. Whipple disease, caused by Tropheryma whipplei, is a rare infectious condition primarily presenting with malabsorptive diarrhea. Small bowel biopsies typically reveal foamy macrophages containing periodic acid-Schiff-positive/diastase (PAS/D) resistant T. whipplei bacilli, and PAS(D) staining is occasionally requested by clinicians in duodenal biopsies, which are often histologically unremarkable. The yield of PAS(D) staining in such biopsies has never been reported to our knowledge. Methods. The anatomic pathology database was searched for all specimens of duodenal biopsies stained with PAS(D) from 1993 to 2021. Specimens were categorized by the following histomorphologic features: unremarkable, nonspecific changes, or expansion of the lamina propria by aggregates of foamy histiocytes. Follow-up information was collected, including microbiologic confirmatory testing. Results. There was a total of 193 specimens of duodenal biopsies stained with PAS(D). Biopsies lacking foamy histiocytes on H&E (n = 158) were never PAS-positive. Thirteen biopsies contained PAS-positive histiocytes; 9 out of the 13 PAS-positive specimens were subsequently confirmed to be T. whipplei. Of the 193 specimens, 124 specimens had a clinical request for PAS(D) staining. Only 3 of the 124 (2.4%) specimens showed foamy histiocytes containing PAS-positive granules, all of which were confirmed positive for T. whipplei. Conclusion. PAS(D) staining is unnecessary to exclude Whipple disease in duodenal biopsies without foamy macrophage aggregates, regardless of clinical suspicion. Clinical suspicion-driven biopsies often yield negative results for Whipple disease.