Learn about your diagnosis

Esophagus – Adenocarcinoma

by Jason  Wasserman, MD PhD FRCPC, reviewed on November 22, 2019.

Quick facts:
  • Adenocarcinoma is a type of esophageal cancer.
  • Adenocarcinoma starts on the inside of the esophagus close to the stomach.
  • Adenocarcinoma is associated with a pre-cancerous disease called Barretts esophagus.
  • Many patients also have a long history of acid reflux disease or GERD.
The normal esophagus

The esophagus is a long hollow tube that starts at the back of your throat and ends at the top of your stomach. Swallowed food travels down the esophagus into the stomach.

normal esophagus mucosa

The wall of the esophagus is made up of six layers of tissue:

  • Epithelium – This is the tissue on the inside surface of the esophagus. The epithelium is made up of cells called squamous cells. The squamous cells connect together to form a barrier that protects the inside of the esophagus from injury.
  • Lamina propria – The lamina propria is a thin layer of connective tissue directly below the epithelium. The lamina propria supports the squamous cells.
  • 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, lymphatic channels, and glands.
  • Muscularis propria – The muscularis propria is a thick bundle of muscle in the middle of the wall of the esophagus. The muscularis propria allows the esophagus to move food towards the stomach.
  • Adventitia – The tissue on the outer surface of the esophagus is called the adventitia. It surrounds the esophagus and separates is from nearby tissues and organs such as the airway and the aorta.
Acid reflux and Barretts esophagus

Certain conditions, such as long standing acid reflux (acid splashing up from the stomach into the esophagus) cause the squamous cells to be replaced by a type of epithelium that looks similar to epithelium from the small bowel. This change is called Barretts esophagus.

What is adenocarcinoma?

Adenocarcinoma is a type of esophageal cancer. Most patients with adenocarcinoma of the esophagus have had Barretts esophagus for many years. For this reason, Barretts esophagus is considered a pre-cancerous condition that can lead to adenocarcinoma.

Adenocarcinoma is the most common type of esophageal cancer in developed countries and it is more common in men than women.

The diagnosis of adenocarcinoma is usually made after a small sample of tissue is removed in a procedure called a biopsy and the tumour is later removed  in a resection specimen such as an esophagectomy. In many cases a portion of the stomach is removed at the same time.

Histologic grade

Grade is a word pathologists use to describe how different the cancer looks compared to normal, healthy tissue. Because adenocarcinoma develops from tissue which looks like small bowel (Barretts esophagus), the grade for adenocarcinoma of the esophagus is based on how different the cancer cells look compared to the normal, healthy 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. The grade is divided into four levels which range from tumours with lots of glands to tumours with few if any 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 – Less than 50% of the tumour is made up of glands.
  4. Undifferentiated – There are no glands seen anywhere in the tumour.

Why is this important? Grade is important because poorly differentiated and undifferentiated tumours are associated with worse prognosis and are more likely to spread to other parts of the body (metastasize).

Tumour site

The esophagus is a long tube that extends from the top of the neck to the stomach. In your report, tumour site refers to the part of the esophagus or stomach involved by the tumour. Most adenocarcinomas start near the end of the esophagus (the distal portion) or the area where the esophagus meets the stomach (the gastroesophageal junction; see below).

Relationship of tumour to the gastroesophageal junction

The gastroesophageal junction is the area where the esophagus meets the stomach. The location of the tumour relative to this area is important because tumours that start completely within the esophagus (above the junction) or just slightly below the junction, are called esophageal tumours. Those that start below the junction and are entirely within the stomach are called gastric tumours.

Why is this important? Esophageal and gastric tumours are treated differently and have different prognosis. Talk to your doctor about the location of your tumour and the treatment options available.

Tumour size

After the tumour has been removed fully, your pathologist will measure it in three dimensions although only the largest dimension is typically included in your report. For example, if the tumour measures 5.0 cm by 3.2 cm by 1.1 cm, the report may describe the tumour size as 5.0 cm in greatest dimension.

Tumour extension

The esophagus is a tube and the wall of the tube is made up of six different layers of tissue (see above). Adenocarcinoma starts in the epithelium on the inner surface of the esophagus. 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 esophagus. 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 esophagus. The amount of tumour extension can usually only be seen after the entire tumour has been removed.
  • Adventitia – The adventitia is the tissue on the outside surface of the esophagus. The adventitia separates the esophagus from other organs that are near the esophagus in the neck or chest. Once the cancer cells pass the adventitia they are outside of the esophagus and able to spread into other organs.

Why is this important? 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 wall of the esophagus or surrounding organs are more likely to come back after treatment in the area of the original tumour or spread (metastasize) to a distant site such as the lungs.

Dysplasia and Barrett’s esophagus

Invasive adenocarcinoma in the esophagus develops from the pre-cancerous condition Barretts esophagus. Before turning into cancer, the cells in Barretts esophagus usually start to show an abnormal pattern of growth called dysplasia. For this reason, it is not uncommon for your pathologist to describe seeing Barretts esophagus and dysplasia in addition to the adenocarcinoma.

Perineural invasion

Nerves are like long wires made up of groups of cells called neurons. Nerves transmit information (such as temperature, pressure, and pain) between your brain and your body.

Perineural invasion is a term pathologists use to describe cancer cells attached to a nerve. Cancer cells that have attached to a nerve can use the nerve to travel into tissue outside of the original tumour.

Why is this important? Perineural invasion is associated with a higher risk that the tumour will come back in the same area of the body (local 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.

Margins

In the esophagus, a margin is any tissue that was cut by the surgeon in order to remove the tumour from your body. The types of margins present will depend on the type of procedure that was performed.

For esophagectomy specimens where an entire segment of esophagus has been removed, the margins will include:

  • Proximal margin – This margin is located near the upper portion of the esophagus closer to the mouth.
  • Distal margin – This margin is located near lower portion of the esophagus. The distal margin can be in the esophagus or the stomach.
  • Radial margin – This is the tissue around the outside of the esophagus.

For endoscopic resections where only a small piece of the inside of the esophagus has been removed, the margins will include:

  • Mucosal margin – This is the tissue that lines the inner surface of the esophagus.
  • Deep margin – This tissue is inside the wall of the esophagus. It is located below the tumour.

In the esophagus, a margin is considered positive when there are cancer cells at the very edge of the cut tissue.

Why is this important? A positive margin is associated with a higher risk that the tumour will re-grow 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

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.

Lymph nodes from the neck are sometimes removed at the same time as the main tumour in a procedure called a neck dissection. The lymph nodes removed usually come from different areas of the neck and each area is called a level. The levels in the neck include 1, 2, 3, 4, and 5. Your pathology report will often describe how many lymph nodes were seen in each level sent for examination.

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.

Why is this important? 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).

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)

Adenocarcinoma is given a tumour stage between 1 and 4 based on the distance the cancer cells have traveled from the epithelium on the inner surface of the esophagus into the wall of the esophagus.​

  • Tis – The cancer cells are still only in the epithelium on the inner surface of the esophagus. Another name for this type of tumour is high grade dysplasia.
  • T1a – The cancer cells have broken out of the epithelium and have entered the lamina propria, muscularis mucosae, or submucosa. This stage is often given the special name intramucosal adenocarcinoma.
  • T1b – The cancer cells have entered the submucosa.
  • T2 – The cancer cells have entered the muscularis propria in the middle of the wall.
  • T3 – The cancer cells are in the adventitia on the outer surface of the esophagus.
  • T4 – The cancer cells have traveled beyond the esophagus into surrounding organs or tissues such as the lungs or aorta.

Nodal stage (pN)

Adenocarcinoma is given a nodal stage between 0 and 3 based on the presence of cancer cells in a lymph node and the number of lymph nodes involved.

  • 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 more then six 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)

Adenocarcinoma is given a metastatic stage of 0 or 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 X.

HER2

HER2 is a special type of protein called a receptor. 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 cases of esophageal cancers produce extra HER2, 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. 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? Specific treatments are available for patients with HER2 producing tumours. Talk to your doctor about the HER2 status of your tumour and the treatment options available for you.

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