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Difficulty: HardPathology and Biopsy Interpretation

A 56-year-old man presents to the clinic with an 8-month history of chronic, non-bloody diarrhea, a 12-kg (26-lb) weight loss, and migratory pain in his large joints. His wife notes that over the past two months, he has developed mild memory deficits and unusual, involuntary rhythmic eye movements synchronized with chewing. Physical examination reveals generalized lymphadenopathy and a low-grade fever. Laboratory testing demonstrates a hemoglobin of 9.8 g/dL with a mean corpuscular volume of 92 fL, and a serum albumin of 2.6 g/dL. Upper gastrointestinal endoscopy shows thickened, pale, and edematous duodenal folds. A duodenal mucosal biopsy is submitted for histopathologic evaluation to establish the diagnosis.

Which of the following histopathologic and staining findings are most characteristic of the expected underlying etiology in this patient? (Select all that apply)

  1. Dense infiltration of the lamina propria by foamy macrophages containing Periodic acid-Schiff (PAS)-positive, diastase-resistant inclusions.Answer
  2. Presence of intracellular, Gram-positive, non-acid-fast bacilli within the mucosal histiocytes.Answer
  3. C
    Severe villous blunting accompanied by marked crypt hyperplasia and an increased number of intraepithelial lymphocytes.
  4. D
    Accumulation of foamy macrophages in the lamina propria that demonstrate strong positivity on acid-fast bacilli (AFB) staining.
  5. E
    Mucosal acute inflammation with prominent crypt abscess formation, architectural distortion, and basal plasmacytosis.

Answer

The expected biopsy findings for Whipple disease include a dense infiltration of the lamina propria by foamy macrophages containing PAS-positive, diastase-resistant inclusions, and the identification of Gram-positive, non-acid-fast bacilli.
This patient's presentation of chronic diarrhea, severe weight loss, migratory arthralgias, and pathognomonic neurologic signs (oculomasticatory myorhythmia and cognitive deficits) is highly specific for Whipple disease. This systemic infection is caused by Tropheryma whipplei, a Gram-positive, non-acid-fast bacillus. Diagnosis is typically established via upper endoscopy and duodenal biopsy. The classic histopathologic finding is the expansion of the lamina propria by a dense infiltrate of foamy macrophages. These macrophages contain intact and partially degraded bacteria that appear as abundant granular inclusions. These inclusions stain strongly with Periodic acid-Schiff (PAS) and resist digestion with diastase. It is crucial to differentiate T. whipplei from Mycobacterium avium complex (MAC), which can also cause a malabsorption syndrome with PAS-positive foamy macrophages in the duodenum; however, MAC is acid-fast positive, while T. whipplei is acid-fast negative. Therefore, both the PAS-positive, diastase-resistant inclusions and the Gram-positive, non-acid-fast staining characteristics are expected to confirm the diagnosis.

Step-by-Step Solution

1
Analyze the patient's clinical presentation, including chronic diarrhea, profound weight loss, migratory arthralgias, and oculomasticatory myorhythmia.
The combination of malabsorption, joint pain, and pathognomonic neurologic findings strongly points to Whipple disease.
Recognizing the systemic and highly specific neurologic manifestations is required to form the correct primary differential diagnosis.
2
Determine the causative organism for Whipple disease and its microbiological characteristics.
The disease is caused by Tropheryma whipplei, which is a Gram-positive, non-acid-fast bacillus.
Microbiological properties dictate the special staining patterns expected on the biopsy.
3
Identify the expected histopathologic changes in the duodenum caused by this organism.
The biopsy characteristically shows the lamina propria expanded by foamy macrophages packed with the bacteria, which appear as PAS-positive, diastase-resistant inclusions.
This is the pathognomonic morphologic hallmark required to confirm the diagnosis pathologically.
4
Differentiate the findings from potential pathologic mimics, particularly Mycobacterium avium complex (MAC).
While MAC also produces PAS-positive foamy macrophages, it is acid-fast positive. Therefore, specifying that the bacilli are non-acid-fast is critical for confirming Whipple disease.
Accurate biopsy interpretation requires excluding mimicking conditions through specific staining profiles.

Key Concept

Whipple disease is characterized by duodenal lamina propria expansion with foamy macrophages containing PAS-positive, diastase-resistant inclusions, which represent Gram-positive, non-acid-fast bacilli (Tropheryma whipplei).
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Topics

Pathology and Biopsy Interpretation

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