Well Differentiated Neuroendocrine Tumor of the Stomach: Understanding Your Pathology Report

Section Editor: David Driman
November 11, 2026

A well-differentiated neuroendocrine tumor of the stomach is a type of cancer that starts in hormone-producing cells in the stomach lining. These cells are called neuroendocrine cells. Most of these tumors grow very slowly, and many are small and found by chance during an endoscopy. An older name for this tumor is carcinoid tumor, and your report may use either name.

Doctors divide neuroendocrine tumors of the stomach into three types, and the type has a large effect on how the tumor behaves and how it is treated. This article explains the three types of neuroendocrine tumor of the stomach, how the tumor is graded and staged, and what the other findings in your pathology report mean.

What causes a neuroendocrine tumor of the stomach?

Most neuroendocrine tumors of the stomach are caused by long-term exposure to high levels of gastrin. Gastrin is a hormone that tells the stomach to make acid. It also signals certain neuroendocrine cells in the stomach, called enterochromaffin-like (ECL) cells, to grow. When gastrin levels stay high for many years, these cells multiply and can eventually form a tumor.

The most common cause of high gastrin levels is atrophic gastritis, especially the autoimmune type. In atrophic gastritis, the glands that make stomach acid are damaged and lost. The body responds to the low acid by making more and more gastrin. A much less common cause is a gastrin-producing tumor called a gastrinoma, which is usually found in the pancreas or small intestine.

Some neuroendocrine tumors of the stomach develop without high gastrin levels. The cause of these tumors is not known.

What are the symptoms of a neuroendocrine tumor of the stomach?

Many neuroendocrine tumors of the stomach cause no symptoms. They are often found during an endoscopy to evaluate anemia or as part of follow-up for atrophic gastritis. When symptoms occur, they may include:

Bleeding and anemia. The tumor can bleed slowly, which can lead to anemia, tiredness, or dark stools.
Abdominal pain or indigestion. Larger tumors can cause pain, nausea, or a feeling of fullness after eating.
Symptoms of the underlying condition. People with atrophic gastritis may have symptoms of low vitamin B12. People with a gastrinoma may have repeated ulcers and diarrhea.
Flushing and diarrhea. Rarely, a tumor that has spread to the liver releases hormones that cause flushing of the skin, diarrhea, or wheezing. This is called carcinoid syndrome.

How is the diagnosis made?

The diagnosis of a neuroendocrine tumor of the stomach is usually made after a biopsy taken during an upper endoscopy. Small tumors are often removed completely during the endoscopy using a procedure called endoscopic mucosal resection or endoscopic submucosal dissection. A pathologist then examines the tissue under a microscope.

Under the microscope, a well-differentiated neuroendocrine tumor consists of small, uniform cells arranged in nests, cords, or small glands. The cells have round nuclei with finely speckled chromatin, which pathologists often describe as a “salt and pepper” pattern. The term well differentiated means the tumor cells still look a lot like normal neuroendocrine cells.

Your doctor will often also take biopsies from the normal-looking lining in different parts of the stomach. These biopsies show whether atrophic gastritis is present, which helps determine the type of tumor. They may also show ECL cell hyperplasia, an increase in ECL cells caused by high gastrin levels. A blood test for gastrin and imaging such as an endoscopic ultrasound or CT scan may also be used, especially for tumors larger than 1 cm.

Immunohistochemistry

Immunohistochemistry is a test that uses antibodies to show which proteins are present in cells. For a neuroendocrine tumor of the stomach, it confirms that the tumor cells are neuroendocrine cells and helps separate the tumor from adenocarcinoma, the most common type of stomach cancer. Your report may describe some of the following results.

Synaptophysin and chromogranin. The tumor cells are positive for synaptophysin and chromogranin. These proteins are found in neuroendocrine cells and confirm the diagnosis.
INSM1. The tumor cells are usually positive for INSM1, another neuroendocrine marker.
Cytokeratins. The tumor cells are positive for cytokeratins, which shows that they come from the lining of the stomach.
Ki-67. Ki-67 shows how many tumor cells are dividing. The result is used to assign the grade, as described below.

Not every laboratory performs every one of these tests, so your report may include only some of them.

What are the different types of neuroendocrine tumor of the stomach?

The World Health Organization (WHO) classification (5th edition, 2019) divides well differentiated neuroendocrine tumors of the stomach into three types. Your pathology report may not state the type directly, because it depends on information from your doctor, blood tests, and the biopsies of the surrounding stomach lining.

Type 1. Type 1 tumors make up about 70% to 80% of neuroendocrine tumors of the stomach. They develop in people with atrophic gastritis and high gastrin levels. They are usually small, often multiple, and almost always grade 1 or grade 2. Type 1 tumors very rarely spread, and the outlook is excellent.
Type 2. Type 2 tumors make up about 5% of neuroendocrine tumors of the stomach. They develop in people with a gastrinoma, a condition called Zollinger-Ellison syndrome. Many of these people have an inherited condition called multiple endocrine neoplasia type 1 (MEN1). Type 2 tumors are also usually small and multiple, but they spread more often than type 1 tumors.
Type 3. Type 3 tumors make up about 15% to 25% of neuroendocrine tumors of the stomach. They develop without high gastrin levels or atrophic gastritis. They are usually single and larger, and they can be any grade. Type 3 tumors are the most likely to spread to lymph nodes and the liver.

Histologic grade

The grade of a neuroendocrine tumor of the stomach describes how quickly the tumor cells are dividing. Pathologists use two measurements to decide the grade. One is the number of dividing cells, called mitotic figures, counted in an area of 2 square millimeters. The other is the Ki-67 index, the percentage of tumor cells that stain with Ki-67. When the two measurements disagree, assign the higher grade.

Grade 1 (G1). Fewer than 2 mitotic figures per 2 square millimeters and a Ki-67 index below 3%. Grade 1 tumors grow very slowly.
Grade 2 (G2). 2 to 20 mitotic figures per 2 square millimeters or a Ki-67 index of 3% to 20%. Grade 2 tumors grow a little faster.
Grade 3 (G3). More than 20 mitotic figures per 2 square millimeters or a Ki-67 index above 20%. Grade 3 tumors grow faster and are more likely to spread. A well differentiated grade 3 tumor is different from a poorly differentiated neuroendocrine carcinoma, which is a much more aggressive cancer.

Tumor size and number

The size of a neuroendocrine tumor of the stomach is one of the most important findings in your report. Tumors 1 cm or smaller rarely spread, while larger tumors carry a higher risk. If more than one tumor is present, which is common in type 1 tumors, your report will usually give the number of tumors and the size of the largest one.

Depth of invasion

Depth of invasion describes how far a neuroendocrine tumor of the stomach has grown into the stomach wall. Most small tumors are found in the lamina propria or the submucosa, the layers just below the surface. Tumors that reach the thick muscle layer, called the muscularis propria, or go beyond it are more likely to spread. Depth of invasion helps determine the tumor stage.

Lymphovascular invasion

Lymphovascular invasion means that cells from the neuroendocrine tumor were seen inside a blood vessel or lymphatic channel. Tumor cells can use these vessels to spread to lymph nodes and other organs. Finding lymphovascular invasion increases the risk of spread, and it may lead your doctors to recommend further treatment after an endoscopic removal.

Perineural invasion

Perineural invasion means that cells from the neuroendocrine tumor were seen along or around a nerve. It is uncommon in small stomach tumors. When present, it is usually seen in larger tumors that have grown deeper into the stomach wall.

Margins

A margin is the edge of the tissue that was cut to remove the neuroendocrine tumor of the stomach. For an endoscopic removal, the pathologist checks the deep margin at the bottom of the tissue and the mucosal margins around the sides. For a surgical removal of part of the stomach, the pathologist checks the proximal, distal, and omental margins.

Negative margin. No tumor cells are seen at the cut edge, which means the tumor was likely removed completely.
Positive margin. Tumor cells are seen at the cut edge, which means some of the tumor may have been left behind. For small type 1 tumors, a positive margin does not always need more treatment, and your doctor may recommend close follow-up instead.

Lymph nodes

Lymph nodes are only removed when part of the stomach is removed by surgery, which is more common for type 3 tumors. The pathologist examines each lymph node under a microscope to look for tumor cells. Your report will give the number of lymph nodes examined and the number that contain tumor. Finding tumor cells in a lymph node is called a metastasis and increases the stage.

Pathologic stage (pTNM)

The pathologic stage of a neuroendocrine tumor of the stomach is based on the AJCC staging system (Version 9, in use since January 2024). The stage is assigned only after the tumor has been removed, and it is often not given for small tumors removed during endoscopy. The stage combines the tumor stage (pT), the nodal stage (pN), and, when known, distant spread (pM).

Tumor stage (pT)

pT1. The tumor has grown into the lamina propria or submucosa and is 1 cm or smaller.
pT2. The tumor has grown into the muscularis propria, or it is larger than 1 cm.
pT3. The tumor has grown through the muscularis propria into the tissue just below the outer surface of the stomach.
pT4. The tumor has grown through the serosa (the outer surface of the stomach) or into nearby organs.

If more than one tumor is present, the letter “m” may be added to the tumor stage, for example pT1(m).

Nodal stage (pN)

pN0. No tumor cells were found in the examined lymph nodes.
pN1. Tumor cells were found in at least one nearby lymph node.
pNX. No lymph nodes were sent for examination.

Metastatic stage (pM)

Distant spread is only included in the pathology report when a tumor sample from another organ has been examined. The category pM1a means spread to the liver only, pM1b means spread to sites outside the liver, and pM1c means spread to both.

What is the prognosis?

The prognosis for a person with a well differentiated neuroendocrine tumor of the stomach depends mostly on the type, size, grade, and stage of the tumor. For type 1 tumors, the outlook is excellent, and more than 95% of people are alive 5 years after the diagnosis. Type 1 tumors may come back in the stomach because the atrophic gastritis that caused them is still present, but these new tumors are usually small and easy to remove.

Type 2 tumors also have a good outlook, although about 10% to 30% spread to lymph nodes or other organs. Type 3 tumors behave more like other stomach cancers, and more than half have spread by the time they are found. For all types, small grade 1 tumors confined to the lamina propria or submucosa have the best outlook.

What happens after the diagnosis?

Treatment for a neuroendocrine tumor of the stomach depends mostly on the type and size of the tumor. The European Neuroendocrine Tumor Society (ENETS) published guidance on managing these tumors in 2023.

Type 1 tumors. Small type 1 tumors are often monitored with regular endoscopies, and tumors larger than 1 cm are usually removed endoscopically. Surgery is considered only for larger tumors that cannot be removed endoscopically or that have high-risk features. The first follow-up endoscopy is usually within 12 months, then every one to three years.
Type 2 tumors. Treatment focuses on the gastrinoma causing the high gastrin levels. The stomach tumors are often removed during endoscopy or watched.
Type 3 tumors. A small grade 1 tumor under 1 cm may be removed during endoscopy. Most type 3 tumors are treated with surgery to remove part of the stomach and the nearby lymph nodes.
Tumors that have spread. Medications called somatostatin analogs, such as octreotide and lanreotide, are often used first to slow tumor growth. Other options include everolimus, chemotherapy, and a targeted radiation treatment called lutetium-177 oxodotreotide (Lutathera). Health Canada approved Lutathera in 2019 for tumors that have spread or cannot be removed and are growing.

People with type 1 tumors also need follow-up for atrophic gastritis itself, which can cause low vitamin B12 levels and slightly increase the risk of stomach adenocarcinoma.

Questions to ask your doctor

What type of neuroendocrine tumor do I have, type 1, type 2, or type 3?
Do I have atrophic gastritis, and what caused it?
How large was the tumor, and wwerethere mmultiple tumors
What grade is the tumor, and what was the Ki-67 index?
How deeply did the tumor grow into the stomach wall?
Was lymphovascular invasion seen?
Was the tumor removed completely, and were the margins negative?
Do I need imaging or a blood test for gastrin?
Do I need surgery, or can the tumor be watched or removed during endoscopy?
How often will I need follow-up endoscopies?
Should I be checked for vitamin B12 deficiency?
Should I be tested for an inherited condition such as MEN1?