Older Male with Weight Loss > 50 lbs

Laura E. Michael, D.O.

Specimen Type:

Small Intestine


46 year old male with weight loss greater than 50 lbs. and arthritis. On upper endoscopy (EGD) slightly raised yellowish-white nodule is found in the duodenum and biopsied.

Pathologic Features:

Duodenal villi are expanded by foamy histocytes with characteristic spaces / vacuoles noted.

  • Positive - coarse dark staining of organisms
  • Acid fast stain: negative

Differential Diagnosis:

  • Mycobacterium avium-intracellulare
  • Signet ring cell carcinoma
  • Xanthelasma
  • Whipple’s disease


Whipple’s Disease

Whipple’s disease is a rare chronic systemic illness first described more than 90 years ago as intestinal lipodystrophy. Patients most commonly suffer from severe weight loss, chronic arthralgias and abdominal discomfort, but the symptoms vary due to the concentration of organisms in the involved organs. The typical histologic picture is as presented, with large histocytes crowding the lamina propria, distorting villi, and alternating with empty spaces. The empty spaces are usually not seen in Mycobacterium avium-intracellulare AIDS enteropathy. The disease is not restricted to the bowel. Macrophages / histocytes containing the organisms can be found in the rest of the alimentary tract, regional and peripheral lymph nodes, heart, lungs, liver, spleen, adrenal glands and nervous system.

The organism involved is Tropheryma whippelli, which can not be cultured. Electron Microscopy has traditionally been used to confirm the diagnosis, demonstrating bacillary bodies in the histocytes. Since the 1990’s Polymerase Chain Reaction (PCR) assay has been used to confirm the diagnosis as well as verify treatment success. PCR detects a portion of the 16S ribosomal RNA gene sequence corresponding to the T. whippelli bacillus. The conversion on antibiotic therapy of the positive PCR tissue samples into negative occur before significant histologic improvement.


  1. Whipple GH. A hitherto undescribed disease characterized anatomically by deposits of fatty acids in the intestinal and mesenteric lymphatic tissue. Bull Johns Hopkins Hosp. 1907; 18:382-391.
  2. Dobbins WOI. Current concepts of Whipple’s Disease. J Clin Gastroenterol 1982; 4: 205-208.
  3. Petrides, PE, PCR analysis of T. Whippelli DNA in a case of Whipple’s disease: effect of antibiotics and correlation with histology. American Journal of Gastroenterology 93 (9), 1579-1582.