Periodic acid Schiff positive macrophages are seen in:

Correct Answer: D. Whipple’s disease

Whipple's disease is caused by the Gram-positive bacterium Tropheryma whipplei, which is pathognomonic for PAS-positive, diastase-resistant macrophages in the lamina propria of the small intestine. The PAS-positive material represents bacterial cell wall glycoprotein debris that accumulates within macrophages. This is the hallmark histopathological finding on small bowel biopsy—foamy macrophages packed with PAS-positive granules that are resistant to diastase digestion (unlike glycogen, which is diastase-sensitive). The disease presents with chronic diarrhea, malabsorption, weight loss, and arthralgia, predominantly affecting middle-aged males in India and worldwide. The PAS-positive macrophages are so characteristic that their presence on biopsy is virtually diagnostic of Whipple's disease. Electron microscopy reveals rod-shaped bacteria within the macrophages. Treatment with prolonged antibiotics (typically starting with IV ceftriaxone followed by oral trimethoprim-sulfamethoxazole for 1 year) leads to clinical and histological resolution, with disappearance of the PAS-positive macrophages.

Why the other options are wrong

A. Abetalipoproteinemia — Abetalipoproteinemia is a lipid malabsorption disorder characterized by absence of apolipoprotein B, leading to fat-laden enterocytes and lipid droplets in the lamina propria. The pathology shows lipid accumulation, NOT PAS-positive macrophages. Histology reveals acanthocytes in blood and lipid-laden intestinal epithelium, not the characteristic foamy macrophages seen in Whipple's disease. B. Crohn's disease — Crohn's disease is characterized by non-caseating granulomas in the lamina propria and submucosa, NOT PAS-positive macrophages. While Crohn's can present with diarrhea and malabsorption similar to Whipple's, the histological hallmark is granulomatous inflammation with epithelioid cells and Langhans giant cells, which are PAS-negative. This is a common NBE trap pairing two malabsorption disorders. C. Agammaglobulinemia — Agammaglobulinemia (X-linked Bruton's hypogammaglobulinemia) is an immunodeficiency characterized by absent B cells and hypogammaglobulinemia, leading to recurrent infections and chronic diarrhea. However, the intestinal pathology does not show PAS-positive macrophages. Instead, there is villous atrophy and lymphocytic infiltration. The diarrhea is due to infection and malabsorption, but the specific PAS-positive macrophage finding is absent.

High-Yield Facts

Mnemonics

PAS-Positive Macrophages = Whipple's PAS-Positive = Pathognomonic for Whipple's. Remember: 'PAS-P = W' — when you see foamy macrophages with PAS-positive granules on small bowel biopsy, think Whipple's disease immediately. Diastase Resistance Confirms Bacteria Diastase Resistance = Bacterial origin. Glycogen (storage disease) is diastase-sensitive; bacterial cell wall debris (Whipple's) is diastase-resistant. Use this to differentiate on histology.

NBE Trap

NBE pairs Whipple's disease with Crohn's disease as both cause chronic diarrhea and malabsorption, luring students to confuse the granulomatous inflammation of Crohn's with the PAS-positive macrophages of Whipple's. The key discriminator is the presence of non-caseating granulomas in Crohn's versus foamy PAS-positive macrophages in Whipple's.</trap> <parameter name="textbookRef">Robbins Ch. 17 (GIT pathology); Harrison Ch. 297 (Whipple's disease)

Clinical Pearl

In India, Whipple's disease is rare but should be suspected in any patient with chronic diarrhea, malabsorption, and unexplained weight loss who has traveled or lived in endemic areas. Small bowel biopsy with PAS staining is diagnostic and guides early antibiotic therapy, preventing complications like endocarditis and CNS involvement.