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Difficulty: MediumPathology and Biopsy Interpretation

A 34-year-old woman is evaluated in the gastroenterology outpatient clinic for a 6-month history of chronic, non-bloody, voluminous diarrhea and a 4-kg (8.8-lb) weight loss. She also reports severe, generalized fatigue. On physical examination, her vital signs are within normal limits. Skin examination reveals an intensely pruritic, papulovesicular eruption symmetrically distributed over her extensor surfaces, particularly the elbows, knees, and buttocks. Laboratory studies demonstrate a microcytic anemia with a remarkably low serum ferritin level. The physician strongly suspects an underlying immune-mediated gastrointestinal disorder and performs an esophagogastroduodenoscopy with multiple biopsies from the distal duodenum. Which of the following histopathologic findings are characteristic of this patient's underlying condition and would most likely be observed on the biopsy specimen? (Select all that apply)

  1. Villous blunting and atrophyAnswer
  2. Increased number of intraepithelial lymphocytesAnswer
  3. C
    Noncaseating granulomas in the lamina propria
  4. D
    Foamy macrophages containing periodic acid-Schiff (PAS)-positive, diastase-resistant inclusions
  5. E
    Thickened subepithelial collagen band

Answer

The correct histologic findings are villous blunting and atrophy, and an increased number of intraepithelial lymphocytes.
The patient's clinical presentation of chronic diarrhea, significant weight loss, iron deficiency anemia, and an intensely pruritic vesicular rash on the extensor surfaces (dermatitis herpetiformis) establishes a strong clinical diagnosis of celiac disease (gluten-sensitive enteropathy). To confirm this diagnosis, an esophagogastroduodenoscopy with duodenal biopsy is performed. The classic triad of histopathologic findings in celiac disease includes an increased number of intraepithelial lymphocytes, crypt hyperplasia, and varying degrees of villous blunting and atrophy. These changes are primarily seen in the distal duodenum, where the concentration of gluten and the resulting immune response are highest.

Step-by-Step Solution

1
Analyze the clinical presentation to identify the most likely underlying diagnosis.
The combination of chronic diarrhea, weight loss, iron deficiency anemia, and a pruritic papulovesicular rash on extensor surfaces (dermatitis herpetiformis) strongly indicates celiac disease.
Dermatitis herpetiformis is pathognomonic for celiac disease, and the malabsorptive symptoms support this immune-mediated enteropathy.
2
Determine the characteristic histopathologic features of the identified disease on duodenal biopsy.
Celiac disease is characterized histologically by villous atrophy/blunting, crypt hyperplasia, and intraepithelial lymphocytosis.
Exposure to gliadin triggers an inflammatory cascade in susceptible individuals, leading to characteristic mucosal changes in the small intestine.
3
Evaluate the given options to select the features that match the histopathology of celiac disease.
Villous blunting and increased intraepithelial lymphocytes correctly match the pathology. Granulomas, PAS-positive macrophages, and a thickened collagen band belong to other distinct gastrointestinal pathologies.
Accurate biopsy interpretation requires matching specific microscopic patterns to their corresponding clinical syndromes.

Key Concept

The classic histopathologic features of celiac disease on duodenal biopsy include villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes.
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Topics

Pathology and Biopsy Interpretation

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