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Microscopic Features of Whipple Disease: There is usually marked enlargement of mesenteric and periaortic lymph nodes in Whipple disease. The nodal architecture is distorted by numerous poorly-formed lipophagic granulomas and cystic spaces. Epithelioid and foreign body giant cells may be present, but there is no necrosis.

There are aggregates of foamy histiocytes containing PAS-positive diastase-resistant material which is most likely residue of partially-digested bacilli. The foamy granular material is also gram-positive and silver (GMS stain) positive and acid-fast negative (an important distinguishing feature from MAI granulomas). Rare cases show monoclonal B-cell proliferation or even frank lymphomas.

Image courtesy of: ARP Press; used with permission

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