Your pathology report for celiac disease

Jason Wasserman MD PhD FRCPC
September 17, 2025

Celiac disease is a condition where the body reacts abnormally to gluten, a protein found in wheat, barley, and rye. This reaction causes inflammation and damage to the lining of the small intestine. The damage is caused by immune cells called lymphocytes, which are found in increased numbers in the small intestine of people with celiac disease. Another name for celiac disease is gluten-sensitive enteropathy.

What are the symptoms of celiac disease?

Celiac disease can cause many different symptoms, and the severity varies widely. Some people have no apparent symptoms, while others may have severe problems. Symptoms can involve the digestive system or other parts of the body.

Digestive symptoms may include:

• Diarrhea (frequent, loose, watery stools).

• Constipation (difficulty or infrequent bowel movements).

• Abdominal pain, bloating, or cramps.

• Excess gas.

• Nausea or vomiting.

• Unexplained weight loss.

Other symptoms may include:

• Fatigue and low energy.

• Anemia (often due to iron deficiency).

• Bone or joint pain.

• Itchy, blistering skin rash (dermatitis herpetiformis).

• Mouth ulcers.

• Headaches or migraines.

• Numbness or tingling in the hands or feet, balance problems, or memory difficulties.

• Menstrual changes, infertility, or missed periods in women.

• Mood changes such as depression, anxiety, or irritability.

What causes celiac disease?

Celiac disease happens when the immune system reacts to gluten and mistakenly attacks the lining of the small intestine. This damage prevents nutrients from being absorbed properly. The exact reason this happens is not fully understood, but it involves a mix of genetic, environmental, and immune factors.

• Genetic factors – Most people with celiac disease have specific genes called HLA-DQ2 or HLA-DQ8. These genes affect how the immune system responds to gluten. Having these genes alone is not enough to cause the disease, but they increase the risk.
• Environmental factors – Eating foods that contain gluten triggers an immune reaction in people with celiac disease. Some infections, especially in childhood, may increase the risk of developing the disease in those who are genetically predisposed. The timing and amount of gluten introduced into an infant’s diet may also play a role.
• Immune factors – In celiac disease, the immune system creates an autoimmune response. This means it mistakenly attacks the body’s own tissue—in this case, the lining of the small intestine—whenever gluten is present.

How is the diagnosis of celiac disease made?

Doctors use a combination of blood tests and a biopsy of the small intestine to diagnose celiac disease.

• Blood tests look for antibodies against tissue transglutaminase (anti-TTG). Most people with celiac disease will have these antibodies if they are eating gluten.
• Biopsy samples are usually taken from the second part of the duodenum (the beginning of the small intestine). Pathologists examine these samples under the microscope to look for the changes typical of celiac disease.

What does celiac disease look like under the microscope?

A healthy duodenum has:

• Tall, finger-like villi that absorb nutrients.

• Short, shallow crypts (glands that make new cells).

• A thin lining of cells called enterocytes that absorb food.

• Goblet cells that produce protective mucus.

• Only a few lymphocytes (immune cells).

In celiac disease, pathologists may see the following changes:

• Villous atrophy – The villi become shorter or completely flattened, reducing the surface area available for nutrient absorption.
• Villous blunting – The villi are shortened but not completely flattened. This may be an early sign of celiac disease or a sign of partial healing.
• Crypt hyperplasia – The crypts become larger and more numerous as the intestine tries to repair itself.
• Intraepithelial lymphocytosis – The number of lymphocytes between the cells of the lining increases, often to more than 25 for every 100 surface cells. This is a key feature of celiac disease.

Modified Marsh classification

Pathologists often use the modified Marsh classification to grade the microscopic changes in celiac disease. This system helps describe the severity of damage.

• Marsh 0 – Normal tissue with no changes.

• Marsh 1 – Increased lymphocytes but normal villi.

• Marsh 2 – Increased lymphocytes plus crypt hyperplasia.

• Marsh 3a – Partial villous atrophy with mild blunting.

• Marsh 3b – Subtotal villous atrophy with more severe blunting.

• Marsh 3c – Total villous atrophy with complete flattening of the villi.

Questions for your doctor

If you have been diagnosed with celiac disease, you may wish to ask your doctor:

• What did my biopsy show, and what Marsh classification was reported?

• Were my blood tests positive for celiac disease antibodies?

• Do I need to see a dietitian to help with a gluten-free diet?

• How will we monitor my recovery and long-term health?

• Do I need any follow-up tests to check for nutrient deficiencies such as iron, calcium, or vitamin D?

• Should my family members also be tested for celiac disease?