Intraepithelial lymphocytosis describes an abnormally high number of lymphocytes — a type of immune cell — found within the epithelium, which is the thin layer of cells that lines the inner surfaces of organs such as the intestines, stomach, cervix, and airways. A small number of lymphocytes in the epithelium is normal, but when their numbers increase significantly beyond the expected range, pathologists describe this as intraepithelial lymphocytosis. This finding tells your doctor that the immune system is actively responding to something in the tissue — most often an infection, an autoimmune condition, or a medication effect.
What does intraepithelial lymphocytosis look like under the microscope?
A pathologist identifies intraepithelial lymphocytosis by counting lymphocytes within the epithelial layer of the tissue sample. Lymphocytes are small, dark-staining cells with large, round nuclei. When present in the epithelium in elevated numbers — nestled between the normal surface cells — they are immediately recognizable as being out of place.
In many organs, pathologists use a defined threshold to decide when the number is abnormal. For example, in the small intestine, more than 25 lymphocytes per 100 epithelial cells is generally considered elevated and raises the possibility of celiac disease or another cause. In the colon, more than 20 intraepithelial lymphocytes per 100 epithelial cells is used as a diagnostic threshold for lymphocytic colitis. These numbers help standardize the diagnosis and ensure that reporting is consistent.
What conditions are associated with intraepithelial lymphocytosis?
The significance of intraepithelial lymphocytosis depends on where in the body it is found:
- Small intestine — celiac disease — the most important cause of intraepithelial lymphocytosis in the small intestine. In celiac disease, eating gluten triggers an immune response that causes lymphocytes to accumulate in the lining of the small bowel. Intraepithelial lymphocytosis in the duodenum (the first section of the small intestine) is one of the earliest and most consistent features of celiac disease, even before the intestinal villi (the tiny finger-like projections that aid absorption) begin to flatten.
- Stomach — Helicobacter pylori infection and autoimmune gastritis — H. pylori infection is a common bacterial cause of intraepithelial lymphocytosis in the stomach lining. Autoimmune gastritis, in which the immune system attacks stomach cells, can also produce this pattern.
- Colon — lymphocytic colitis and microscopic colitis — when intraepithelial lymphocytosis in the colon meets a defined threshold and is accompanied by surface epithelial damage, the diagnosis of lymphocytic colitis is made. This is a form of microscopic colitis — a condition that causes chronic watery diarrhea but appears normal on colonoscopy, requiring biopsy to diagnose. NSAIDs and certain other medications are common triggers.
- Cervix and vagina — intraepithelial lymphocytosis can occur in the cervical or vaginal epithelium in response to infections, chronic inflammation, or other irritants. In this context, it is usually a reactive finding and does not indicate precancerous change.
- Other causes — infections (including certain viral infections), inflammatory bowel disease such as Crohn’s disease, medication reactions, and other autoimmune conditions can all produce intraepithelial lymphocytosis in various locations.
What does finding intraepithelial lymphocytosis in my report mean?
Intraepithelial lymphocytosis is not a diagnosis on its own — it is a microscopic pattern that points toward an underlying cause. Finding it in your report means the pathologist has identified an increased number of lymphocytes in the epithelial lining of the tissue sampled, and your doctor will use this information alongside your symptoms, blood tests, and other findings to determine what is causing it.
In many cases — particularly in the small intestine — this finding leads to straightforward follow-up testing, such as blood tests for celiac disease antibodies or breath testing for H. pylori. The finding itself is not dangerous, and many of the conditions it points to are very manageable once identified. Intraepithelial lymphocytosis does not mean cancer.
Questions to ask your doctor
- Where was the intraepithelial lymphocytosis found, and what conditions does my doctor think are most likely causing it?
- What further tests are needed to identify the cause?
- Does this finding require treatment? If so, what are my options?
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