Your pathology report for intramucosal adenocarcinoma of the esophagus

by Catherine Forse MD FRCPC and Jason Wasserman MD PhD FRCPC
February 20, 2026

Intramucosal adenocarcinoma of the esophagus is an early-stage cancer that arises from gland-forming cells lining the esophagus.

The esophagus is the muscular tube that carries food from the mouth to the stomach. Its innermost layer is called the mucosa. When cancer cells are described as intramucosal, it means the tumor is confined to this inner layer and has not spread into deeper tissues.

Because the tumor is limited to the mucosa, intramucosal adenocarcinoma is considered an early and potentially curable stage of cancer. Many patients are treated successfully with minimally invasive procedures such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD).

What are the symptoms?

Some people have no symptoms, especially when the tumor is detected early during routine surveillance for Barrett’s esophagus.

When symptoms occur, they are often related to the underlying condition rather than the cancer itself. These symptoms may include difficulty swallowing, chest discomfort, worsening heartburn, or unexplained weight loss.

What causes intramucosal adenocarcinoma?

Most intramucosal adenocarcinomas develop in patients with Barrett’s esophagus.

Barrett’s esophagus occurs when the normal squamous cells lining the esophagus are replaced by gland-forming cells that resemble cells normally found in the intestine. This change is called intestinal metaplasia. It develops over time due to long-term exposure to stomach acid from chronic acid reflux, also known as gastroesophageal reflux disease.

Over time, the glandular cells in Barrett’s esophagus can develop abnormal changes called dysplasia. Dysplasia may progress from low-grade to high-grade and eventually to intramucosal adenocarcinoma.

How is this diagnosis made?

The diagnostic process usually begins with an upper endoscopy, during which abnormal areas are identified. A biopsy or endoscopic resection is performed, and the tissue is examined under a microscope by a pathologist.

The diagnosis of intramucosal adenocarcinoma is made only after microscopic examination confirms that cancer cells are present and confined to the mucosa.

Microscopic features

Under the microscope, intramucosal adenocarcinoma is composed of abnormal gland-forming cells growing within the mucosa. The glands are often irregular in shape and size and may appear crowded, fused, or back-to-back. The tumor cells typically have enlarged, dark-staining nuclei, which are the parts of the cells that contain genetic material.

Cancer cells may invade the lamina propria, a thin layer of supportive tissue beneath the surface epithelium, or the muscularis mucosae, a thin muscle layer at the base of the mucosa. However, the tumor does not extend into the submucosa, which lies deeper and contains larger blood vessels and lymphatic channels.

Pathologists carefully examine multiple tissue levels to confirm that invasion is confined to the mucosa.

Immunohistochemistry

Immunohistochemistry may be performed to support the diagnosis or to evaluate biomarkers. Tumor cells typically express cytokeratin markers such as CK7 and often express CDX2, which reflects their origin in Barrett-related glandular epithelium. Additional tests may be performed if the tumor has unusual features.

Histologic grade

Intramucosal adenocarcinoma is divided into three grades based on how closely the tumor cells resemble normal gland-forming cells.

• In well-differentiated tumors (Grade 1), most of the tumor forms recognizable glands that resemble normal structures.
• In moderately differentiated tumors (Grade 2), gland formation is still present but less organized.
• In poorly differentiated tumors (Grade 3), fewer gland structures are seen, and the tumor cells appear more abnormal and disorganized.

Higher-grade tumors tend to behave more aggressively.

Depth of invasion and pathologic tumor stage (pT)

Intramucosal adenocarcinoma begins in the mucosa, the innermost layer of the esophageal wall. Assessing the depth of invasion involves understanding how deeply the tumor has grown.

The mucosa is made up of three layers: the surface epithelium, the lamina propria, and the muscularis mucosae. Beneath the mucosa lies the submucosa, which contains larger blood vessels and lymphatic channels. Deeper still is the muscularis propria, a thick muscle layer.

In intramucosal adenocarcinoma, the tumor invades into the lamina propria or muscularis mucosae but does not extend into the submucosa. Because invasion is limited to the mucosa, these tumors are assigned a pathologic tumor stage of pT1a.

This distinction is very important. Once a tumor extends into the submucosa (pT1b), the risk of spread to lymph nodes increases significantly. For this reason, confirming that the tumor is limited to the mucosa helps guide treatment decisions and supports the use of endoscopic therapy in appropriate patients.

Lymphovascular invasion

Lymphovascular invasion (LVI) means that cancer cells are seen inside small blood vessels or lymphatic channels. This finding increases the risk that cancer cells could spread beyond the original site. It is reported as present or absent.

Perineural invasion

Perineural invasion (PNI) means that cancer cells are growing around or into a nerve. This is uncommon in intramucosal adenocarcinoma but, if present, may indicate more aggressive behavior.

Margins

A margin is the edge of the tissue removed during EMR, ESD, or surgery. The pathologist examines the margins to determine whether cancer cells reach the edge of the specimen.

In endoscopic resections, margins are described as:

• Lateral (mucosal) margins, which represent the side edges of the removed tissue.

• Deep (vertical) margin, which represents the deepest portion of the specimen.

A negative margin means no cancer cells are seen at the edge. A positive margin means cancer cells extend to the edge, suggesting that additional treatment may be needed. The distance between the tumor and the margin may also be measured and reported.

Biomarkers

Biomarkers are proteins or molecular features tested in tumor tissue that may help guide treatment decisions.

HER2

HER2 is a protein that promotes cell growth. Some esophageal adenocarcinomas produce too much HER2.

HER2 is tested using immunohistochemistry. Results are typically reported as 0, 1+, 2+, or 3+. A score of 3+ is considered positive. A score of 2+ is considered equivocal and usually requires additional testing. HER2-positive tumors may respond to HER2-targeted therapy.

Mismatch repair (MMR) proteins

MMR proteins help repair errors in DNA. The four main proteins tested are MLH1, PMS2, MSH2, and MSH6.

Results are usually described in the pathology report as retained (normal) or lost expression. Retained expression means all four proteins are present and functioning normally. Loss of expression of one or more proteins suggests that the DNA repair system is not working properly. Tumors with loss of MMR protein expression may exhibit microsatellite instability and respond better to certain types of immunotherapy.

If MMR protein loss is identified, additional testing may be recommended to evaluate for Lynch syndrome, an inherited condition that increases the risk of several cancers.

PD-L1

PD-L1 is a protein that helps cancer cells avoid detection by the immune system. PD-L1 is tested using immunohistochemistry, and results are reported using a Combined Positive Score (CPS). A CPS of 1 or higher may increase the likelihood that immunotherapy will be beneficial.

Claudin 18.2

Claudin 18.2 is a protein normally found in cells lining the stomach. Some adenocarcinomas of the esophagus and stomach express this protein.

Claudin 18.2 testing is performed using immunohistochemistry. Results are often reported as the percentage of tumor cells showing positive staining. For example, a report may state that 60% of tumor cells express claudin 18.2. A higher percentage of positive tumor cells may make the patient eligible for targeted therapies directed against this protein. Although testing is more commonly performed in advanced disease, it may be included in certain cases.

Questions to ask your doctor

• Were the margins negative?

• Was lymphovascular or perineural invasion present?

• What is the tumor grade?

• Do I need additional treatment or surveillance?

• Were biomarker tests performed, and what do the results mean for my treatment?