Stomach – Adenocarcinoma

by Jason Wasserman, MD PhD FRCPC, reviewed on June 1, 2020

Quick facts:

• Adenocarcinoma is a type of stomach cancer.
• It develops from the cells that line the inside of the stomach.
• Pathologists divide adenocarcinoma of the stomach into two groups, intestinal type and diffuse type, based how the cancer cells look through the microscope.

In this article you will learn about:

• The anatomy and histology of the stomach
• What is adenocarcinoma?
• Your biopsy report for adenocarcinoma
• Your pathology report after the tumour has been removed
• Types of adenocarcinoma
• Tumour grade
• Tumour size
• Tumour extension​
• Perineural invasion​
• Lymphovascular invasion​
• Lymph nodes
• Margins
• Treatment effect
• Pathologic stage
• HER2

The anatomy and histology of the stomach

The stomach is a hollow organ found near the middle of your abdomen. Food that you eat travels down your esophagus into the stomach. The stomach is responsible for breaking down and absorbing food so that it can be used by your body.

The stomach is made up of six layers of tissue:

• Epithelium – This is  the inside surface of the stomach. The epithelium is made up of specialized epithelial cells that connect together to form glands. Some of these cells produce acid which helps your stomach breakdown food. Other cells produce mucus which protects the lining of the stomach from the acid inside.
• Lamina propria – The lamina propria is a thin layer of connective tissue directly below the epithelium. The lamina propria supports the glands.
• Muscularis mucosa – The muscularis mucosa is a thin layer of muscle cells below the lamina propria.
• Submucosa – The submucosa sits directly below the muscularis mucosa. It contains large blood vessels and lymphatic channels.
• Muscularis propria – The muscularis propria is a thick bundle of muscle in the middle of the stomach. The muscularis propria allows the stomach to mix and break down the food you eat.
• Subserosal soft tissue – This is a layer of tissue near the outer surface of the stomach. Most of the subserosal soft tissue is made up of fat.
• Serosa– The serosa is a thin layer of tissue on the outside surface of the stomach. It surrounds the stomach and separates is from nearby tissues and organs such as the spleen, colon, liver, diaphragm, pancreas, adrenal gland, kidney, and small intestine. Another name for the serosa is the visceral peritoneum.

What is adenocarcinoma?

Adenocarcinoma is a type of stomach cancer. It starts from the cells in the epithelium on the inside of the stomach. There are two different types of adenocarcinoma that can start in the stomach:

• Intestinal type adenocarcinoma.
• Diffuse (signet cell) type adenocarcinoma.

See the section called Types of adenocarcinoma (below) to learn more.

In many cases, adenocarcinoma starts from a pre-cancerous disease called intestinal metaplasia. Intestinal metaplasia occurs when the epithelium normally found in the stomach becomes damaged and is replaced by the type of epithelium that is normally found in the small bowel.

Your biopsy report for adenocarcinoma

A biopsy is a surgical procedure that removes a small piece of tissue for examination by a pathologist. The purpose of a biopsy is to establish a diagnosis. A test called immunohistochemistry may be performed to confirm the diagnosis.

Other information that may be included in your biopsy report are the type of adenocarcinoma and the tumour grade. The results of a test to look for a protein called HER2 may also be described.

Your doctors will use this information to plan treatment such as surgery, radiation, and chemotherapy. Continue reading to learn more about tumour grade and extension in adenocarcinoma.

Your pathology report after the tumour has been removed

After the tumour has been removed completely, it will be sent to a pathologist who will prepare another pathology report. This report will confirm or revise the original diagnosis and provide additional important information such tumour size, extension, and spread of tumour cells to lymph nodes. This information is used to determine the cancer stage and to decide if additional treatment is required.

Continue reading to learn more about the information found in this report.

Types of adenocarcinoma

There are different types of adenocarcinoma in the stomach and each is called a histologic type. The histologic type of your tumour can only be determined after a sample of the tumour is examined under a microscope by your pathologist. The histologic type is based on the shape and size of the cancer cells and the way the cancer cells stick together.

The two most common histologic types of adenocarcinoma in the stomach are:

• Intestinal type – When examined under the microscope, these tumours look similar to the types of tumours that normally in the small intestine or colon. This type of adenocarcinoma usually starts from the pre-cancerous condition called intestinal metaplasia.
• Diffuse (signet cell ) type – When examined under the microscope, these tumours are made up of cells that do not stick together as the tumour grows. The tumour cells are round and the inside of the cell is filled with a material called mucin. Pathologists call these cells signet cells. This type of tumour can be harder to diagnosis because the individual tumour cells are harder to see under the microscope.

The histologic type is important because the diffuse type has a higher chance of spreading to other parts of the body and is associated with worse prognosis.

There are other types of adenocarcinoma in the stomach but they are rare and will not be discussed in this article.

Tumour grade

Grade is a word pathologists use to describe the difference between the tumour cells and normal, healthy tissue. Because most adenocarcinomas develop from from the pre-cancerous condition intestinal metaplasia (which looks like small bowel), the grade for adenocarcinoma of the stomach is actually is based on how different the cancer cells look compared to the cells in the small bowel.

The normal, healthy small bowel is made up of small round structures called glands. For this reason, adenocarcinoma is given a grade based on how much of the tumour is made up of glands:

1. Well differentiated – More than 95% of the tumour is made up of glands.
2. Moderately differentiated – 50% to 95% of the tumour is made up of glands.
3. Poorly differentiated or undifferentiated – Less than 50% of the tumour is made up of glands. All diffuse type adenocarcinomas are considered poorly differentiated (grade 3).

Compared to well and moderately differentiated tumours, poorly differentiated tumours grow faster and are more likely to spread to other parts of the body.

Tumour size

This is the size of the tumour measured in centimetres. Tumour size will only be described in your report after the entire tumour has been removed. The tumour is usually measured in three dimensions but only the largest dimension is described in your report. For example, if the tumour measures 4.0 cm by 2.0 cm by 1.5 cm, your report will describe the tumour as being 4.0 cm.

Tumour extension​

Adenocarcinoma starts in the epithelium on the inner surface of the stomach. The movement of cancer cells from the epithelium into the tissue below is called invasion.

Tumour extension describes how far the cancer cells have spread from the epithelium into the layers of tissue below.

Your pathology report will describe the tumour extension as follows:

• High grade dysplasia – The cancer cells are only found  in the epithelium of the stomach. This is a non-invasive form of cancer. High grade dysplasia is also called carcinoma in situ.
• Intramuscosal – The tumour is called intramucosal if the cancer cells have not spread any further than the lamina propria or muscularis mucosa.
• Submucosal – Submucosal means that the cancer cells have passed the muscularis mucosa and are into the submucosa.
• Muscularis propria – The muscularis propria is the thick bundle of muscle in the middle of the stomach. This amount of tumour extension can usually only be seen after the entire tumour has been removed.
• Subserosal soft tissue – Cancer cells in the subserosal soft tissue are near the outer surface of the stomach.
• Serosa – Cancer cells that pass the serosa on on the outside surface of the stomach. From here, cancer cells are able to spread to nearby organs such as the spleen, pancreas, small intestine, colon, adrenal gland, or kidney.

Tumour extension is important because it is used to determine the pathologic tumour stage (see Pathologic stage below). Cancer cells that have spread further into the stomach or surrounding organs are more likely to come back after treatment in the area of the original tumour or spread to another part of the body.

Perineural invasion​

Nerves are like long wires made up of groups of cells called neurons. Nerves send information (such as temperature, pressure, and pain) between your brain and your body. Perineural invasion means that cancer cells were seen attached to a nerve.

Cancer cells that have attached to a nerve can use the nerve to travel into tissue outside of the tumour. This increases the risk that the tumour will come grow back in the same area of the body (recurrence) after treatment.

Lymphovascular invasion​

Blood moves around the body through long thin tubes called blood vessels. Another type of fluid called lymph which contains waste and immune cells moves around the body through lymphatic channels.

Cancer cells can use blood vessels and lymphatics to travel away from the tumour to other parts of the body. The movement of cancer cells from the tumour to another part of the body is called metastasis.

Before cancer cells can metastasize, they need to enter a blood vessel or lymphatic. This is called lymphovascular invasion.

Lymphovascular invasion increases the risk that cancer cells will be found in a lymph node or a distant part of the body such as the lungs. In particular, cancer cells seen inside a large vein outside of the tumour is associated with a high risk that the cancer cells will eventually be found in the lung or liver.

Lymph nodes

Lymph nodes are small immune organs located throughout the body. Cancer cells can travel from the tumour to a lymph node through lymphatic channels located in and around the tumour (see Lymphovascular invasion above). The movement of cancer cells from the tumour to a lymph node is called a metastasis.

Your pathologist will carefully examine each lymph node for cancer cells. Lymph nodes that contain cancer cells are often called positive while those that do not contain any cancer cells are called negative. Most reports include the total number of lymph nodes examined and the number, if any, that contain cancer cells.

Finding cancer cells in a lymph node is associated with an increased risk that the cancer cells will spread to other parts of the body. The number of lymph nodes with cancer cells is also used to determine the nodal stage (see Pathologic stage below).

Margins

A margin is any tissue that was cut by the surgeon in order to remove the tumour from your body. Whenever possible, surgeons will try to cut tissue outside of the tumour to reduce the risk that any cancer cells will be left behind after the tumour is removed.

The margins described in your report will depend on how much tissue was removed with the tumour. If the tumour was small and located in the middle of the stomach, all of the margins may be within the stomach. If the tumour was larger or located near the esophagus or small bowel, there may also be a margin in the esophagus or in an area of the small bowel called the duodenum.

Your pathologist will carefully examine all the margins in your tissue sample to see how close the cancer cells are to the edge of the cut tissue. Margins will only be described in your report after the entire tumour has been removed.

A margin is called positive when there are tumour cells at the very edge of the cut tissue. A positive margin is associated with a higher risk that the tumour will recur in the same site after treatment. A negative margin means that no tumour cells were seen at any of the cut edges of tissue.

Treatment effect

​If you received treatment (either chemotherapy or radiation therapy) for your cancer prior to the tumour being removed, your pathologist will examine all of the tissue submitted to see how much of the tumour is still alive (viable).

The treatment effect will be reported on a scale of 0 to 3 with 0 being no viable cancer cells (all the cancer cells are dead) and 3 being extensive residual cancer with no apparent regression of the tumour (all or most of the cancer cells are alive).

Lymph nodes with cancer cells will also be examined for treatment effect.

Pathologic stage

​The pathologic stage for adenocarcinoma is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer.

This system uses information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M)  to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each part a number. In general, a higher number means more advanced disease and worse prognosis.

Pathologic stage is not reported on a biopsy specimen. It is only reported when the entire tumour has been removed in an excision or resection specimen.

Tumour stage (pT) for adenocarcinoma of the stomach

Your pathologist will give a tumour stage from Tis to T4 based on how far the cancer cells have spread from the epithelium on the inner surface of the stomach into the tissue below.

• Tis – The cancer cells are seen only within the epithelium on the inner surface of the stomach. This stage is also known as carcinoma in situ or high-grade dysplasia.
• T1a – The cancer cells have spread into the lamina propria or muscularis mucosa just below the epithelium.
• T1b – The cancer cells have spread into the submucosa.
• T2 – The cancer cells have spread into the muscularis propria.
• T3 – The cancer cells are in the tissue just below the outer surface of the stomach in the subserosal soft tissue.
• T4a – The cancer cells have gone through the serosa and are on the outer surface of the stomach.
• T4b – The cancer cells have spread into organs near the stomach.​

Nodal stage (pN) for adenocarcinoma of the stomach

Adenocarcinoma is given an nodal stage between N0 and N3 based on the number of lymph nodes with cancer cells.

• N0 – No cancer cells are seen in any of the lymph nodes examined.
• N1 – Cancer cells are seen in one or two lymph nodes.
• N2 – Cancer cells are seen in three to six lymph nodes.
• N3a – Cancer cells are seen in seven to fifteen lymph nodes.
• N3b – Cancer cells are seen in more than fifteen lymph nodes.
• NX – No lymph nodes were sent to pathology for examination.

Metastatic stage (pM) for adenocarcinoma of the stomach

Adenocarcinoma is given a metastatic stage between 0 and 1 based on the presence of cancer cells at a distant site in the body (for example the lungs). The metastatic stage can only be determined if tissue from a distant site is submitted for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as MX.

HER2

HER2 is protein made by cells throughout the body. HER2 behaves like a switch that allows cells to grow and divide. Some cancer cells produce extra amounts of HER2 which allows them to grow and divide much faster than normal cells.

One out of every five tumours in the stomach produce extra HER2. For this reason, your pathologist will order a test to look for HER2 in the cancer cells.

The most common test used to look for HER2 in cancer cells is called immunohistochemistry. Another test that is used to look for HER2 is called fluorescence in situ hybridization (FISH).

If immunohistochemistry was performed on the tumour, your report will describe the results as:

• Negative (0 or 1) – The cancer cells are not producing extra HER2.
• Equivocal (2) – The cancer cells may be producing extra HER2.
• Positive (3) – The cancer cells are definitely producing extra amounts of HER2.

Some treatments are only offered to patients with HER2 producing (positive) tumours. Talk to your doctor about the treatment options available for you.