Adenocarcinoma of the Stomach: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
April 5, 2026

Adenocarcinoma is the most common type of stomach cancer, accounting for about 90 to 95% of all cases. It starts in the gland-forming cells that line the inside of the stomach — cells that normally produce mucus and digestive juices to protect the stomach and help it break down food. In adenocarcinoma, these cells grow uncontrolled, forming a tumor that can invade deeper layers of the stomach wall and spread to other parts of the body.

This article will help you understand the findings in your pathology report — what the terms mean, what the numbers indicate, and why each piece of information matters for your care.

What causes adenocarcinoma of the stomach?

Stomach adenocarcinoma develops over time due to a combination of environmental, infectious, and genetic factors. The most common risk factors include:

• Chronic Helicobacter pylori (H. pylori) infection — This bacterium damages the stomach lining and causes long-standing inflammation, which over many years can progress to intestinal metaplasia (a precancerous change in the stomach lining) and eventually cancer. H. pylori is the most important modifiable risk factor for stomach cancer worldwide.
• Epstein-Barr virus (EBV) infection — EBV is found in approximately 10% of stomach adenocarcinomas. EBV-positive tumors tend to have a distinct biology and may respond differently to certain treatments, including immunotherapy.
• Diet and lifestyle — Diets high in salt-preserved or smoked foods, low in fruits and vegetables, and heavy tobacco use all increase risk.
• Inherited genetic conditions — A small but important subset of stomach cancers is caused by inherited gene mutations. CDH1 gene mutations cause hereditary diffuse gastric cancer, a syndrome in which affected individuals have a very high lifetime risk of diffuse-type (signet ring cell) stomach cancer. Lynch syndrome, caused by inherited mutations in mismatch repair genes, also increases stomach cancer risk. Familial adenomatous polyposis (FAP), caused by APC gene mutations, is associated with fundic gland polyps and a modestly increased gastric cancer risk. If your pathology report shows mismatch repair deficiency or diffuse-type adenocarcinoma, especially in a younger patient, your doctor may recommend genetic counseling to evaluate for an inherited condition.

What are the symptoms?

Many people with early stomach cancer have no symptoms. As the tumor grows, symptoms may include difficulty swallowing (dysphagia), early fullness or bloating after small meals, persistent stomach pain or discomfort, unexplained weight loss, nausea, or vomiting. Some people experience dark or tarry stools or blood in vomit, which can indicate gastrointestinal bleeding. Ongoing blood loss can cause anemia — a low red blood cell count — resulting in fatigue and weakness.

How is the diagnosis made?

The diagnosis is made after a tissue sample is examined under the microscope by a pathologist. The sample is typically obtained during an upper endoscopy (gastroscopy), in which a doctor passes a thin flexible tube with a camera through the mouth into the stomach to examine the lining and take small tissue samples called biopsies from suspicious areas.

Under the microscope, cancer is identified when the normal glandular cells of the stomach lining are replaced by malignant cells that grow in a disorganized pattern and invade deeper tissue. The pathologist describes the histologic type (how the cancer cells are arranged), the grade (how abnormal they look), and whether features such as lymphovascular or perineural invasion are present.

Once cancer is confirmed, imaging studies — typically CT scans of the chest, abdomen, and pelvis — are used to determine how far it has spread. Endoscopic ultrasound (EUS) may be used to assess the depth of tumor growth into the stomach wall, and in some cases, a PET-CT scan is performed to detect active disease throughout the body.

Histologic types

Pathologists classify stomach adenocarcinoma into several types based on how the tumor cells are arranged under the microscope. Knowing the type provides information about behavior and may influence treatment decisions.

• Tubular adenocarcinoma — The most common type. The cancer cells form irregular, tube-like glands that invade the deeper layers of the stomach wall.
• Intestinal-type adenocarcinoma — The tumor cells resemble cells found in the intestine. This type often develops in the setting of chronic H. pylori infection, intestinal metaplasia, or long-standing inflammation.
• Papillary adenocarcinoma — The cancer cells form finger-like projections called papillae. This type tends to be more well-differentiated and slower growing than other types.
• Mucinous adenocarcinoma — The tumor produces large amounts of mucus that collect in pools around the cancer cells. When more than 50% of the tumor is made up of mucus, it is classified as mucinous. This type can be more aggressive and may spread more readily.
• Diffuse-type (poorly cohesive) adenocarcinoma — The cancer cells do not stick together and spread individually through the stomach wall without forming glands. This type can be difficult to detect early, is more likely to infiltrate widely, and tends to have a worse prognosis than intestinal-type tumors.
• Signet ring cell carcinoma — A specific form of diffuse-type adenocarcinoma in which each tumor cell contains a large droplet of mucus that pushes the nucleus to the edge of the cell, giving it a signet ring shape. This subtype tends to behave aggressively. When present in a younger patient, hereditary diffuse gastric cancer (CDH1 mutation) should be considered.

Tumor grade

Grade describes how closely the cancer cells resemble normal stomach cells under the microscope. Tumors that look more like normal cells tend to grow more slowly; tumors that look very abnormal tend to grow faster and spread earlier.

• Grade 1 (well differentiated) — More than 95% of the tumor forms glands. Closely resembles normal stomach tissue.
• Grade 2 (moderately differentiated) — Between 50% and 95% of the tumor forms glands.
• Grade 3 (poorly differentiated) — Less than 50% of the tumor forms glands. Looks quite abnormal.
• Undifferentiated — No gland formation is seen at all.

Diffuse-type adenocarcinomas and signet ring cell carcinomas are, by definition, poorly differentiated or undifferentiated, since their cells do not form glands at all. Your pathology report will include the grade because it helps predict how the tumor is likely to behave and whether additional treatment is needed.

Level of invasion

Invasion refers to how deeply the tumor has grown into the layers of the stomach wall. The stomach wall is made up of several distinct layers:

• Mucosa — the innermost lining, where adenocarcinoma begins. This includes the epithelial cells where cancer starts, a thin connective tissue layer called the lamina propria, and a thin inner muscle layer called the muscularis mucosae.
• Submucosa — a supportive layer of connective tissue beneath the mucosa, containing blood vessels and lymphatic channels.
• Muscularis propria — the thick outer muscle layer that contracts to mix and move food.
• Subserosa — a thin layer of connective tissue just beneath the outer surface.
• Serosa — the smooth outer covering of the stomach that faces the abdominal cavity.

As the tumor grows deeper, it becomes more likely to spread to lymph nodes or distant organs. In advanced cases, the tumor can grow directly into neighboring structures such as the spleen, pancreas, colon, liver, or abdominal wall. The deepest layer the tumor has reached is used to determine the pathologic tumor stage (pT).

Perineural invasion

Perineural invasion means that cancer cells are growing along or around a nerve. Nerves run through the stomach wall and surrounding tissue, and tumor cells that reach them can use them as a pathway into adjacent structures. Perineural invasion is 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 stomach wall. Once inside these vessels, cancer cells can travel to nearby lymph nodes or, through the bloodstream, reach distant organs such as the liver or lungs. Its presence increases the risk of spread and may influence decisions about additional treatment. Your report will state whether lymphovascular invasion is present or absent.

Surgical margins

A margin is the edge of the tissue removed during surgery. The pathologist examines the margin surfaces to determine whether cancer cells are present at the cut edge.

• Negative margin — No cancer cells are found at the cut edge. This suggests the tumor was completely removed in that area.
• Positive margin — Cancer cells are present at the cut edge, raising concern that some cancer may remain in the body. Additional treatment is usually recommended.

In stomach cancer surgery, several margin types are assessed and reported separately:

• Proximal margin — the upper cut end of the stomach specimen, toward the esophagus.
• Distal margin — the lower cut end, toward the small intestine (duodenum).
• Radial (circumferential) margin — the outer soft-tissue surface, particularly important when the tumor is located along the back wall of the stomach, where it is close to adjacent structures. This margin is considered positive if tumor cells are within 1 mm of the edge.
• Omental margin — the edge of the fatty tissue (omentum) attached to the stomach that is removed along with the specimen.

Treatment effect

Many patients with stomach cancer receive chemotherapy before surgery (called neoadjuvant chemotherapy) to shrink the tumor and improve the chances of complete removal. After the operation, the pathologist evaluates how much viable tumor remains and assigns a response score using the modified Ryan scheme:

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

A complete or near-complete response (scores 0–1) is associated with a significantly better prognosis. This score is always interpreted in conjunction with the pathologic stage and other findings.

Lymph nodes

Lymph nodes are small immune organs that can trap cancer cells as they spread through the lymphatic system. During surgery, lymph nodes near the stomach are removed and examined by the pathologist. Your report will state the total number of lymph nodes 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 found in a lymph node, the report may also note whether it has broken through the outer wall of the node — a finding called extranodal extension, which is associated with a worse prognosis. The number of involved lymph nodes is one of the most important factors in staging and in decisions about additional treatment.

Biomarker and molecular testing

Biomarker testing is an essential part of managing stomach adenocarcinoma. The results directly influence treatment recommendations and can identify patients who may benefit from targeted therapy or immunotherapy.

HER2

HER2 (human epidermal growth factor receptor 2) is a protein that promotes cell growth. In some stomach cancers, the HER2 gene is amplified — extra copies are present — causing tumor cells to produce too much HER2 protein. These tumors are called HER2-positive. HER2-targeted therapies such as trastuzumab (Herceptin), often combined with chemotherapy or immunotherapy, have demonstrated significant benefit in HER2-positive advanced gastric cancer.

HER2 is tested by immunohistochemistry (IHC) to measure protein levels, with results scored as 0, 1+, 2+, or 3+. Scores of 0 or 1+ are negative; 3+ is positive; 2+ is equivocal and requires confirmatory testing by fluorescence in situ hybridization (FISH) or another gene amplification assay to determine whether the HER2 gene is truly amplified. HER2 testing is performed at the time of diagnosis for all patients with locally advanced or metastatic gastric adenocarcinoma.

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 mechanism, allowing the immune system to recognize and attack the cancer. PD-L1 testing uses the Combined Positive Score (CPS), which measures PD-L1 expression across both tumor cells and surrounding immune cells.

In stomach cancer, PD-L1 CPS is now routinely tested because it guides first-line treatment decisions in advanced disease. A CPS of 1 or higher indicates that immunotherapy combined with chemotherapy may be beneficial. Higher CPS values (≥5 or ≥10) are associated with greater benefit from checkpoint inhibitors in some clinical settings. Your report will state the CPS score, and your oncologist will explain how it applies to your treatment options.

Mismatch repair (MMR) protein testing

Mismatch repair proteins — MLH1, PMS2, MSH2, and MSH6 — are part of the cell’s system for fixing small errors in DNA. When one or more are absent from tumor cells, the result is called mismatch repair-deficient (MMR-deficient or dMMR), also known as microsatellite instability-high (MSI-high). When all proteins are present, the result is MMR-proficient (pMMR).

MMR testing is important in stomach cancer for two reasons. First, MMR-deficient tumors may respond particularly well to checkpoint inhibitor immunotherapy. Second, MMR deficiency may indicate Lynch syndrome, an inherited condition caused by a germline mutation in one of the MMR genes that significantly increases the lifetime risk of stomach, colorectal, endometrial, and other cancers. Genetic counseling and testing are usually recommended when MMR deficiency is identified, particularly in younger patients or those with a family history of cancer, as the implications extend to family members.

Claudin 18.2

Claudin 18.2 (CLDN18.2) is a protein normally found in the tight junctions between gastric lining cells. Some stomach cancers continue to express this protein at high levels, making them candidates for targeted therapies that specifically attack cells with Claudin 18.2. The drug zolbetuximab, an antibody that targets Claudin 18.2, is now FDA-approved for use in combination with chemotherapy in Claudin 18.2-positive, HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma.

Testing is done by immunohistochemistry. A tumor is considered positive if 75% or more of the cancer cells show moderate-to-strong membranous staining (2+ or 3+). Your report will describe the staining intensity and percentage of positive cells. If your tumor is Claudin 18.2-positive, your doctor will discuss whether this changes your treatment plan.

For detailed explanations of these and other biomarker tests used in stomach cancer, 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 tumor (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.

Tumor stage (pT)

• pT1a — Tumor is limited to the mucosa.
• pT1b — Tumor has grown into the submucosa.
• pT2 — Tumor has grown into the muscularis propria (main muscle layer).
• pT3 — Tumor has grown through the muscularis propria into the subserosa or pericolorectal connective tissue (without penetrating the serosa).
• pT4a — Tumor has penetrated through the serosa (outer surface) into the abdominal cavity.
• pT4b — Tumor has grown directly into an adjacent organ or structure, such as the spleen, pancreas, colon, liver, or abdominal wall.

Nodal stage (pN)

• pN0 — No cancer found in any lymph nodes examined.
• pN1 — Cancer found in 1 to 2 lymph nodes.
• pN2 — Cancer found in 3 to 6 lymph nodes.
• pN3a — Cancer found in 7 to 15 lymph nodes.
• pN3b — Cancer found in 16 or more lymph nodes.
• pNX — Lymph nodes were not assessed.

What is the prognosis for adenocarcinoma of the stomach?

The prognosis for stomach adenocarcinoma depends on several factors working together. The most important are the pathologic stage — particularly how deeply the tumor has grown into the stomach wall and how many lymph nodes are involved — and whether the tumor was completely removed with negative margins.

Early-stage tumors confined to the mucosa or submucosa (pT1) with no lymph node involvement have the best outlook and are often curable with surgery alone. As the tumor grows deeper or spreads to more lymph nodes, the risk of recurrence increases substantially. Advanced local disease (pT3-T4) or significant lymph node involvement (pN2-N3) typically requires multimodal treatment including chemotherapy before or after surgery.

Additional factors affecting prognosis include tumor grade, histologic type (diffuse-type tumors and signet ring cell carcinomas tend to have a worse prognosis than intestinal-type tumors), the presence of lymphovascular or perineural invasion, and, when neoadjuvant chemotherapy was given, the degree of treatment response. A complete or near-complete pathologic response (Ryan score 0 or 1) is associated with a meaningfully better long-term outcome.

Biomarker results also matter: HER2-positive tumors may respond well to HER2-targeted therapy; MMR-deficient and high PD-L1 CPS tumors may benefit substantially from immunotherapy; and Claudin 18.2-positive tumors now have an approved targeted option. These treatments have improved outcomes for patients with advanced stomach cancer, and clinical trials continue to evaluate new combinations. Your treatment team will consider all of these factors together when discussing your individual prognosis and treatment plan.

What happens after diagnosis?

After diagnosis, your medical team uses your pathology report, imaging results, and overall health to plan treatment. The team typically includes a surgeon, medical oncologist, radiation oncologist, and pathologist. Treatment depends on stage, biomarker results, and your general health.

For resectable disease, most patients receive chemotherapy before surgery (neoadjuvant chemotherapy) to shrink the tumor, followed by surgery to remove the stomach (partial or total gastrectomy) along with regional lymph nodes, followed by further chemotherapy after surgery. If your tumor is HER2-positive, Claudin 18.2-positive, or MMR-deficient, your oncologist will incorporate targeted therapy or immunotherapy into your plan. For advanced or metastatic disease, systemic treatment — guided by biomarker results — is the primary approach.

After treatment, you will have regular follow-up, including clinic visits, blood tests, and periodic imaging. If a significant portion of the stomach was removed, your team will monitor your nutrition, weight, and vitamin levels (particularly vitamin B12, iron, and calcium). It may recommend dietary adjustments or supplements to prevent deficiencies.

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 histologic type and grade does my pathology report show?
• What is the pathologic stage of my cancer (pT and pN), and what does that mean for my prognosis?
• How deeply did the tumor invade the stomach wall, and has it spread to lymph nodes?
• Were the surgical margins clear? Was the tumor completely removed?
• Was lymphovascular or perineural invasion present?
• If I received chemotherapy before surgery, what was the tumor regression score?
• What were the results of HER2 testing, and does my tumor qualify for HER2-targeted therapy?
• What was the PD-L1 CPS score, and does immunotherapy play a role in my treatment?
• Was Claudin 18.2 testing performed, and is my tumor positive?
• Was the cancer tested for mismatch repair deficiency, and should I be referred for genetic counseling to assess for Lynch syndrome or hereditary diffuse gastric cancer?
• What additional treatment is recommended, and in what order will it be given?
• Are there clinical trials available for my stage and tumor profile?
• What follow-up tests and monitoring will I need, and how often?