HDF Case 952556 Whipple s disease 63 yo female complaining of a diarrhea for 2 months, weigth loss (12 Kg in 3 months), and joint pains. Duodenal biopsy performed.
Scanning view, enlarged intestinal villi, with a preserved general architecture.
Villi are slightly reduced in height.
Lamina propria is infiltrated by sheets of large cells.
The cells have a pale, more or less eosinophilic cytoplasm.
The intestinal epithelium is preserved.
The cells have an ovoid regular nucleii, a vacuolar cytoplasm, are macrophages.
The macrophages are negative to Alcian Blue stain (Goblet cells +)
PAS stain discloses diffuse positivity of the macrophages.
Positivity of the cytoplasm is intense and granular or vacuolar.
Whipple's Disease CLINICAL FEATURES This is a rare bacterial infection attributed to Tropheryma whippelii which affects the small bowel in a diffuse fashion but can also involve many other systems.there may be an underlying immunologic defect in these patients, possibly genetically determined, but this has not been clearly established. Typical patients are middle-aged women, who present with fever, malabsorption and weight loss, arthritis, and Iymphadenopathy. Central nervous system manifestations, including ophthalmoplegia and personality change, have been reported in about 10% of patients.
ENDOSCOPIC FINDINGS The mucosal folds appear thickened and are patchily coated with yellow-white material. On closer inspection, these patches or plaques may represent enlarged bulbous villi. Previously, it was believed that the proximal small bowel was always affected in a diffuse fashion. However,some patients may have only spotty involvement of the lamina propria, and some biopsy specimen may not contain any characteristic macrophages. Direct viewing endoscopy offers an advantage because the focal yellow areas can be selectively biopsied.
HISTOLOGIC FEATURES The typical histology is that of massive infiltration of the lamina propria, and of the submucosa to a lesser extent, with foamy macrophages. Rarely, the infiltrate is limited to the submucosa. These macrophages contain the Whipple's bacilli as well as other ingested material. Sometimes the infiltrate may be so extensive as to be associated with a diffuse flat lesion. More commonly, there are mild or moderate abnormalities in villous architecture. After treatment with antibiotics the bacilli disappear and the number of macrophages is markedly reduced, but they appear to persist for months or years. They predominate especially in the lamina propria around the bases of the crypts and in the submucosa.
Differential diagnosis. Histologically, the only other disorder that may cause a problem in differential diagnosis is Mycobacterium avium-intracellulare in patients with AIDS. Acid-fast stains should therefore be done when macrophages are present in the lamina propria. Massive infection with M. avium has been termed pseudo- Whipple's disease, but the macrophages look completely different, even at the light microscopic level. In AIDS in the absence of M. avium, small clumps of unexplained PASpositive macrophages are occasionally observed in the small bowel mucosa, but they are very patchily distributed and the intensity of their PAS positivity is variable. Histoplasmosis may be associated with a macrophage infiltrate, but if that is part of the differential diagnosis clinically, then fungal stains should be done. Involvement of the colon is extremely rare in Whipple's disease.