Adenocarcinoma of the Esophagus: Understanding Your Pathology Report

by Catherine Forse MD FRCPC and Jason Wasserman MD PhD FRCPC
April 3, 2026

Adenocarcinoma of the esophagus is a type of cancer that develops from gland-forming cells in the esophagus’s lining. It almost always starts in the lower part of the esophagus, near where it joins the stomach — an area called the esophagogastric junction. In some cases, it extends into the uppermost part of the stomach. This article will help you understand the findings in your pathology report and what they mean for your care.

What causes adenocarcinoma of the esophagus?

Most esophageal adenocarcinomas develop in people with a condition called Barrett’s esophagus. In Barrett esophagus, the normal flat squamous cells that line the esophagus are gradually replaced by glandular cells that resemble those found in the intestines — a change called intestinal metaplasia. This happens because long-standing gastroesophageal reflux disease (GERD) allows stomach acid and bile to damage the esophageal lining repeatedly.

Over the years, these abnormal glandular cells can acquire further changes and progress to dysplasia — a precancerous condition in which the cells look increasingly abnormal under the microscope. Dysplasia in Barrett’s esophagus is classified as either low-grade or high-grade:

• Low-grade dysplasia — The cells look mildly abnormal. The risk of progressing to cancer is present but relatively low. Careful monitoring or endoscopic treatment is often recommended.
• High-grade dysplasia — The cells appear very abnormal and disorganized. This carries a much higher risk of turning into invasive cancer and frequently exists alongside or adjacent to early adenocarcinoma. Treatment to remove or destroy the abnormal tissue is usually recommended.

If your pathology report mentions dysplasia, it means abnormal but not yet fully invasive cells were found near the tumour. This supports the understanding that the cancer developed through the Barrett esophagus pathway. In some cases — particularly with large or deeply invasive tumors — the surrounding dysplastic tissue may no longer be visible in the specimen.

Other important risk factors include obesity, smoking, male sex, and older age. Esophageal adenocarcinoma is considerably more common in men than women and most often occurs in people over 60.

What are the symptoms?

Common symptoms include difficulty swallowing (dysphagia), particularly with solid foods; heartburn or acid reflux that may have changed in character; unexplained weight loss; chest or upper abdominal pain; nausea; and vomiting. In some cases, the cancer is discovered when investigating anemia caused by slow bleeding from the tumour, or found incidentally during imaging or surveillance endoscopy for known Barrett’s esophagus.

How is the diagnosis made?

The diagnosis is usually made after an upper endoscopy (gastroscopy), during which a doctor uses a thin, flexible camera to examine the esophagus and take small tissue samples (biopsies) from any abnormal areas. These samples are examined under a microscope by a pathologist.

Under the microscope, adenocarcinoma is made up of abnormal gland-forming cells that have invaded through the surface layer of the esophagus into the deeper tissue beneath. The pathologist may describe different growth patterns — tubular, papillary, mucinous, or signet ring cell — which describe how the cancer cells are arranged rather than representing separate subtypes. The most common pattern is tubular. More than one pattern may be seen in the same tumour. If Barrett’s esophagus or dysplasia is visible near the tumour, it will also be mentioned in your report.

If cancer is confirmed on biopsy, additional tests such as endoscopic ultrasound, CT scan, or PET scan are used to assess how deeply the tumour has grown and whether it has spread to lymph nodes or distant organs, before treatment is planned.

Tumour grade

Grade describes how closely the cancer cells resemble normal gland-forming cells of the esophagus. Higher-grade tumors look more abnormal under the microscope and tend to grow faster and spread more readily.

• Grade 1 (well differentiated) — More than 95% of the tumour forms well-organized glands. These tumors tend to grow more slowly and are associated with a better prognosis.
• Grade 2 (moderately differentiated) — Between 50% and 95% of the tumour forms glands. These tumors show more variation in how the cells look and behave, and grow faster than grade 1 tumors.
• Grade 3 (poorly differentiated or undifferentiated) — Less than 50% of the tumour forms glands, and in some cases, no gland formation is seen at all. The cells look very abnormal. These are considered high-grade, aggressive tumors associated with a worse prognosis.

Level of invasion

Invasion refers to how deeply the cancer has grown into the wall of the esophagus or surrounding tissues. The esophageal wall is made up of several distinct layers:

• Mucosa — the innermost lining, where adenocarcinoma begins. The mucosa itself has two sublayers: the lamina propria (a thin layer of connective tissue just below the surface cells) and the muscularis mucosae (a thin inner muscle layer).
• Submucosa — a supportive layer of connective tissue containing blood vessels and lymphatics, lying just beneath the mucosa.
• Muscularis propria — a thick muscle layer that contracts to push food through the esophagus.
• Adventitia — the outermost connective tissue layer anchoring the esophagus in place. Unlike most other parts of the gastrointestinal tract, the esophagus lacks a serosa (smooth outer covering).

As the tumour grows deeper, it can also invade nearby structures such as the trachea (windpipe), aorta, or pericardium (the tissue surrounding the heart). The deepest layer the tumour has reached determines the pathologic tumour stage (pT).

Perineural invasion

Perineural invasion means that cancer cells are growing along or around a nerve. Nerves travel through the tissue surrounding the esophagus, and tumour cells that reach them can use them as a pathway into adjacent tissues. Perineural invasion is considered an aggressive feature associated with a higher risk of local recurrence and spread. Your pathology report will state whether perineural invasion is present or absent.

Lymphovascular invasion

Lymphovascular invasion means that cancer cells have entered small blood vessels or lymphatic channels within or around the esophageal wall. Once inside these vessels, cancer cells can travel to nearby lymph nodes or reach more distant organs through the bloodstream. The presence of lymphovascular invasion increases the risk of spread and may influence treatment decisions, such as the need for chemotherapy or radiation. Your report will state whether lymphovascular invasion is present or absent.

Surgical margins

Margins are the cut edges of tissue removed during surgery. After the tumour is removed, the pathologist examines these edges to determine whether any cancer cells are present at the cut surface.

• Negative margin (clear or uninvolved) — No cancer cells are found at the edge. This suggests the tumour was completely removed in that area.
• Positive margin (involved) — Cancer cells are present at the edge, raising concern that some cancer remains in the body. Additional treatment is usually recommended.

Depending on the type of surgery and the location of the tumour, several different margins may be assessed and reported separately:

• Proximal margin — the upper cut end of the removed esophagus, closest to the mouth.
• Distal margin — the lower cut end, closest to the stomach.
• Radial (circumferential) margin — the outer soft-tissue surface of the esophagus, particularly important for tumors that have grown deeply through the wall. This margin is considered positive if tumour cells are within 1 mm of the edge.
• Deep margin — the tissue directly beneath the tumour.

Treatment effect

Many patients with esophageal adenocarcinoma receive chemotherapy, radiation, or both before surgery (called neoadjuvant therapy) to shrink the tumour and improve the chances of complete removal. After surgery, the pathologist evaluates how much viable tumour remains in the specimen and assigns a treatment response score using the modified Ryan scheme:

• Score 0 — No viable cancer cells remain (complete response). This is the most favorable result and is associated with the best outcomes.
• Score 1 — Only single cancer cells or rare small groups remain (near-complete response). Very few tumour cells survived treatment.
• Score 2 — Residual cancer is present with evidence that the tumour shrank or was affected by treatment (partial response). Treatment helped but did not destroy the tumour completely.
• Score 3 — Extensive residual cancer with no clear evidence that the tumour responded (poor or no response). The tumour looks largely unchanged by treatment.

A complete or near-complete response (scores 0–1) is associated with a significantly better prognosis. The treatment response score is always considered alongside pathologic stage and other findings.

Lymph nodes

Lymph nodes are small immune organs located throughout the body that can trap cancer cells spreading through the lymphatic vessels. During surgery for esophageal adenocarcinoma, nearby lymph nodes are removed and examined by the pathologist. Your report will state how many lymph nodes were examined and how many, if any, contain cancer.

Lymph nodes are described as positive if they contain cancer and negative if they do not. If cancer is present, the report may also note whether the cancer has broken through the outer wall of the node — a finding called extranodal extension, which carries a worse prognosis. The number of positive lymph nodes is used to determine the nodal stage (pN) and is one of the strongest predictors of outcome in esophageal cancer.

Biomarker and molecular testing

Biomarker testing is a standard and essential part of managing esophageal adenocarcinoma. The results directly influence which treatments are recommended, particularly for advanced or metastatic disease.

HER2

HER2 (human epidermal growth factor receptor 2) is a protein that promotes cell growth. In some esophageal adenocarcinomas, the HER2 gene is amplified — meaning extra copies are present — causing the tumour cells to produce too much HER2 protein. These tumors are called HER2-positive. HER2-targeted therapies, such as trastuzumab (Herceptin) and, more recently, combinations with immunotherapy, have shown meaningful benefits in HER2-positive esophageal and gastroesophageal junction cancers.

HER2 is tested in two ways:

• Immunohistochemistry (IHC) — measures the amount of HER2 protein on the tumour cell surface and is reported as a score from 0 to 3+. Scores of 0 or 1+ are negative; 3+ is positive. A score of 2+ is equivocal and requires follow-up testing.
• Fluorescence in situ hybridization (FISH) or other gene amplification tests — performed when the IHC score is 2+ to determine whether the HER2 gene is truly amplified. A positive (amplified) result confirms HER2 positivity.

Your report will state your HER2 IHC score and, if applicable, the result of the gene amplification test. HER2 testing is typically performed at the time of first diagnosis of advanced disease.

PD-L1

PD-L1 is a protein that some cancer cells produce to shield themselves from immune attack. Immunotherapy drugs called checkpoint inhibitors (such as pembrolizumab and nivolumab) work by blocking this shielding mechanism, allowing the immune system to recognize and attack the cancer.

PD-L1 testing in esophageal adenocarcinoma uses the Combined Positive Score (CPS), which measures PD-L1 expression across both tumour cells and surrounding immune cells. A CPS of 1 or higher is considered positive and indicates that immunotherapy may be beneficial, particularly when combined with chemotherapy for advanced disease. A CPS below 1 indicates little or no PD-L1 expression, though immunotherapy may still be considered in certain situations.

PD-L1 CPS testing is now routinely performed for esophageal and gastroesophageal junction adenocarcinomas, as the result influences the choice of first-line treatment in advanced disease.

Mismatch repair (MMR) protein testing

Mismatch repair proteins — MLH1, PMS2, MSH2, and MSH6 — are part of the cell’s DNA repair system. When one or more of these proteins are missing from the tumour cells, the tumour is called mismatch repair deficient (MMR-deficient or dMMR). This is also described as microsatellite instability-high (MSI-high). When all proteins are present, the result is MMR-proficient (pMMR).

MMR deficiency is uncommon in esophageal adenocarcinoma, but when present,t it has two important implications:

• The tumour may respond particularly well to immunotherapy with checkpoint inhibitors.
• MMR deficiency may indicate an inherited condition called Lynch syndrome, which significantly increases the lifetime risk of several cancers, rs including colorectal, endometrial, and others. Further genetic testing and referral to a genetics specialist are usually recommended when MMR deficiency is found in an esophageal cancer, as this may have implications for the patient’s family members.

For detailed explanations of HER2, PD-L1, and MMR testing in upper gastrointestinal cancers, visit our Biomarkers and Molecular Testing section.

Pathologic stage (pTNM)

The pathologic stage is determined after surgery and describes how far the cancer has spread. It uses the internationally recognized TNM staging system, which considers the primary tumour (T), lymph node involvement (N), and distant metastasis (M). The pathologist from the surgical specimen determines the pT and pN stages; the M stage is typically determined by imaging.

Tumour stage (pT)

• pT1a — Cancer is confined to the lamina propria or muscularis mucosae — the thin layers just beneath the surface lining of the esophagus.
• pT1b — Cancer has grown deeper into the submucosa, the connective tissue layer just beneath the mucosa.
• pT2 — Cancer has grown into the muscularis propria (the main muscle layer of the esophageal wall).
• pT3 — Cancer has grown through the muscle layer and into the adventitia (the outermost connective tissue of the esophagus).
• pT4a — Cancer has grown into adjacent resectable structures such as the pleura, pericardium, azygos vein, diaphragm, or peritoneum. Surgery may still be possible.
• pT4b — Cancer has invaded critical structures such as the aorta, vertebral body, or airways. Surgery is usually not possible.

Nodal stage (pN)

• pN0 — No cancer found in any lymph nodes examined.
• pN1 — Cancer found in 1 or 2 lymph nodes.
• pN2 — Cancer found in 3 to 6 lymph nodes.
• pN3 — Cancer found in 7 or more lymph nodes.
• pNX — Lymph nodes were not assessed.

What is the prognosis for adenocarcinoma of the esophagus?

The prognosis for esophageal adenocarcinoma depends on several factors working together. The most important is the pathologic stage at the time of surgery, particularly how deeply the tumour has grown into the esophageal wall and whether lymph nodes are involved. Tumors confined to the inner layers (pT1a or pT1b) with no lymph node involvement have a significantly better prognosis than those that have penetrated the full thickness of the wall or spread to multiple nodes.

Additional factors that influence prognosis include tumour grade (higher grade tutumorsehave more aggressive behavior), the presence of lymphovascular or perineural invasion, margin status (whether the tumour was completely removed), and — when neoadjuvant therapy was given — the degree of treatment response. A complete or near-complete pathologic response to pre-surgical chemotherapy and radiation (score 0 or 1) is associated with a substantially better long-term outcome.

Biomarker results also play a role: HER2-positive tumors may respond very well to HER2-targeted therapy; PD-L1-positive and MMR-deficient tumors may benefit substantially from immunotherapy. These targeted options have improved outcomes meaningfully for patients with advanced disease over the past decade, and new combinations continue to be evaluated in clinical trials.

Your treatment team will consider all of these factors together when discussing your individual prognosis and treatment plan.

Questions to ask your doctor

Your pathology report contains important information that will guide your care. The following questions may help you prepare for your next appointment.

• What is the pathologic stage of my cancer (pT and pN), and what does that mean for my prognosis?
• How deeply did the cancer grow into the esophageal wall?
• Were any lymph nodes involved, and if so, how many?
• Were the surgical margins clear? Was the tumour completely removed?
• Was lymphovascular or perineural invasion present, and how does that affect my treatment plan?
• What was the tumour grade?
• If I received treatment before surgery, what was the tumour regression score, and what does it mean?
• What were the results of HER2 testing, and does my tumour qualify for HER2-targeted therapy?
• What was the PD-L1 CPS score, and does immunotherapy play a role in my treatment?
• Was the cancer tested for mismatch repair deficiency, and should I be referred for genetic counseling to assess for Lynch syndrome?
• Are there clinical trials available for my stage and tumour profile?
• What follow-up tests and imaging will I need, and how often?