What are the histopathological features of celiac disease?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: February 13, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Histopathological Features of Celiac Disease

The histopathological features of celiac disease are characterized by villous atrophy, intra-epithelial lymphocytosis, and crypt hyperplasia of the small bowel 1.

Key Features

  • Villous atrophy can range from mild to severe and is a hallmark of the disease
  • Intra-epithelial lymphocytosis is an increase in the number of lymphocytes within the epithelial layer of the small intestine
  • Crypt hyperplasia is an increase in the depth of the crypts in the small intestine, which can lead to malabsorption of nutrients

Classification Systems

The Marsh classification is a commonly used system to describe the histological changes in celiac disease, which includes:

  • Type 1: increased intra-epithelial lymphocytes
  • Type 2: increased intra-epithelial lymphocytes and crypt hyperplasia
  • Type 3: villous atrophy, which can be further subdivided into:
    • 3a: mild villous atrophy
    • 3b: moderate villous atrophy
    • 3c: severe villous atrophy
  • Type 4: completely flattened and hypoplastic mucosa 1

Importance of Histology

Histology is the gold standard for diagnosis of celiac disease in adults and may also help to differentiate celiac disease-related symptoms from those unrelated to the disease 1. A biopsy finding of villous atrophy is not specific for celiac disease, and the addition of celiac-specific serology is necessary to seal the diagnosis 1.

Biopsy Specimens

It is crucial to take multiple, well-oriented biopsy specimens from the second part of the duodenum or beyond to accurately assess the histological changes in celiac disease 1. The villous to crypt cell ratio should be evaluated in well-oriented biopsy specimens to reduce misdiagnosis 1.

From the Research

Histopathological Features of Celiac Disease

The histopathological features of celiac disease include:

  • Villous atrophy and intraepithelial lymphocytosis, which are characteristic histological lesions resulting from an inappropriate T-cell-mediated immune response against ingested gluten in genetically predisposed individuals 2
  • Architectural abnormalities of the duodenal mucosa, including glandular hyperplasia and villous atrophy 3
  • An increased number of intraepithelial T-lymphocytes, which can be accurately counted using ancillary tests such as anti-CD3 stain 3
  • Crypt hyperplasia and a chronic inflammatory cell infiltrate in the lamina propria 4

Grading of Villous Atrophy

Villous atrophy can be graded according to the villous/crypt (V/C) ratio, with:

  • Grade 1: 2.5-2
  • Grade 2: 1-2
  • Grade 3: 1-0.5
  • Grade 4: less than 0.5 5 Celiac disease is consistently associated with villous atrophy grades 3 and 4, which can fully recover or maintain Grade 1 after a gluten-free diet 5

Diagnostic Approach

The diagnosis of celiac disease requires a joint clinicopathological approach, with:

  • Serology with immunoglobulin A (IgA) tissue transglutaminase and IgA endomysial antibodies as the recommended first-line test 6
  • Biopsy as the gold standard to confirm the diagnosis, with both tests performed before the introduction of a gluten-free diet 6
  • A multidisciplinary team to optimize tissue sampling and interpretation via the interaction between the pathologist and the gastroenterologist 3

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.