Stomach -

Adenocarcinoma

This article was last reviewed and updated on March 14, 2018
by Jason Wasserman, MD PhD FRCPC

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.

 

The normal stomach

The stomach is a hollow organ located in the middle of your abdomen. Food that you eat enters the stomach after traveling down the esophagus. The stomach is responsible for breaking down and absorbing food so that it can be used by your body. The inner surface of the stomach is lined by a layer of cells called epithelium. Under the epithelium is a thin layer of supportive tissue called the lamina propria. Together, the epithelium and lamina propria form a layer called mucosa.

 

What is adenocarcinoma?

Adenocarcinoma of the stomach 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. See the section called Histologic types to learn more.

 

Types of adenocarcinoma in the stomach:

 

  • Intestinal type adenocarcinoma.

  • Diffuse (signet cell) type adenocarcinoma.

 

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.


The diagnosis of adenocarcinoma is usually made after a small sample of tissue is removed in a procedure called a biopsy. Most patients are then offered surgery to remove the entire tumour. Some patients may be offered chemotherapy or other treatments before surgery is performed.

Histological type

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.

 

Why is this important? 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.

Histological grade

Grade is a word pathologists use to describe how different the cancer looks compared to the normal tissue in that location. Because most adenocarcinomas develop from from the precursor 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 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).


Why is this important? Compared to well and moderately differentiated tumours, poorly differentiated are associated with worse prognosis.

Tumour size

These tumours are measured in three dimensions but only the largest dimension is typically included in the report.  For example, if the tumour measures 8.0 cm by 4.1 cm by 2.3 cm, the report may describe the tumour size as 8.0 cm in greatest dimension.  

 

Tumour size is not reported in a biopsy specimen.

Tumour extension
​All adenocarcinomas start in the epithelium on the inner surface of the stomach. Tumour extension describes how far the cancer cells have traveled from the epithelium into the wall of the stomach. The movement of cancer cells from the epithelium into the wall is referred to as invasion.

 

  • Carcinoma in situ or high grade dysplasia - The cancer cells are only seen in the epithelium on the inner surface of the stomach.

  • Lamina propria, muscularis mucosae, and submucosa - These tissues are immediately below the epithelium. Once the cancer cells these tissues, it is referred to as invasive

  • Muscularis propria - The cancer cells have gone through the submucosa and entered a thick bundle of muscle called the muscularis propria in the middle of the wall.

  • Subserosal soft tissue - The cancer cells have passed the thick bundle of muscle and entered the tissue just below the outer surface of the stomach called the subserosal soft tissue. 

  • Serosa and nearby organs - The cancer cells have traveled through the entire wall of stomach and are now at the serosa which lines the outer surface of the stomach. Cancer cells that reach the serosa may enter nearby organs such as the duodenum or esophagus.

Why is this important? Tumour extension is used to determine the pathologic Tumour stage (see Pathologic stage below). Tumours that invade deeper into the wall of the stomach or into nearby organs are associated with worse prognosis.

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.


Why is this important? 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.


Why is this important? 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.

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 considered positive when there are cancer cells at the very edge of the cut tissue.

A negative margin means there were no cancer cells at the very edge of the cut tissue. If all the margins are negative, most pathology reports will say how far the closest cancer cells were to a margin. The distance is usually described in millimeters.

Why is this important? A positive margin is associated with a higher risk that the tumour will grow back (recur) in the same site after treatment.

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.

Lymph nodes
Metastatic disease describes the process where cancer cells escape the main tumour and travel to another part of the body. Lymph nodes are small immune organs located throughout the body. They are a common target for metastatic disease.

 

The presence of cancer cells in a lymph node (also called lymph node metastases) is associated with a higher risk that the cancer cells will be found in other lymph nodes or in a distant organ such as the lungs. For this reason, lymph nodes in the area of the tumour are often removed and submitted for pathological examination.

 

Most reports include the total number of lymph nodes examined and the number that contain cancer cells.

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

All adenocarcinomas of the stomach start in the inner lining of the stomach (the epithelium). Your pathologist will give a tumour stage from Tis to T4 based on how far the cancer cells have traveled from the inner lining into the wall of the stomach or the tissues surrounding the stomach.

  • 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.

  • T1 - The cancer cells have entered the tissue just below the epithelium. These tissues are referred to as the lamina propria, muscularis mucosae, and submucosa.

  • T2 - The cancer cells have entered the thick bundle of muscle (the muscularis propria) in the middle of the wall of the stomach.

  • T3 - The cancer cells have traveled almost through the entire wall and are in the subserosal connective tissue just below the outer surface of the stomach.

  • T4 - The cancer cells have gone through the entire wall of the stomach or have entered surrounding organs such as the esophagus or duodenum.


Nodal stage (pN) for adenocarcinoma of the stomach

Adenocarcinoma is given an nodal stage between 0 and 3 based on the presence or absence of cancer cells inside lymph nodes.

  • 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.

  • N3 - Cancer cells are seen in seven or more lymph nodes.


If no lymph nodes are submitted for pathological examination, the nodal stage cannot be determined and the nodal stage is listed as NX.

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 production

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.

 

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

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