Esophagus -

Adenocarcinoma

This article was last reviewed and updated on April 25, 2019.
by Jason  Wasserman, MD PhD FRCPC

Quick facts:

  • Adenocarcinoma is a type of esophageal cancer.

  • Adenocarcinoma starts on the inside of the esophagus.

  • Adenocarcinoma is associated with a pre-cancerous disease called Barretts esophagus.

  • Many patients also have a long history of acid reflux disease or GERD.

  • Your pathology report for adenocarcinoma includes important information such as the tumour size and the distance the cancer cells have traveled into the wall of the esophagus or surrounding tissues.

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. 

 

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

  • Mucosa - The first layer on the inside of the esophagus is called mucosa. The surface of the mucosa is called the epithelium and it is made up of squamous cells. The epithelium is surrounded by a special type of tissue called lamina propria which provides support for the squamous cells. Right below the lamina propria is a thin group of muscle cells called the muscularis mucosae.

  • Submucosa - The submucosa sits directly below the 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 helps move food from your mouth to your 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 aorta. 

 

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 (see picture below). This change is called Barretts esophagus.

What is adenocarcinoma?

Adenocarcinoma is a type of cancer that typically develops in patients who have had Barretts esophagus for many years. For this reason, Barretts esophagus is considered a pre-cancerous or precursor condition.

 

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 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 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

All adenocarcinomas start in the epithelium on the inside surface of the esophagus. The epithelium is part of the mucosa and is surrounded by lamina propria and a thin group of muscle cells called muscularis mucosae. The layers of tissue below the mucosa include the submucosa, muscularis propria, and adventitia. The movement of cancer cells from the epithelium into the lamina propria or the tissue below the mucosa is called invasion

 

Tumour extension is a way of describing how far the cancer cells have traveled from the epithelium into the tissue below. Your pathologist will carefully examine your tissue to find the cancer cells that have traveled the furthest from the epithelium.

If the cancer cells are only seen in the mucosa (lamina propria and muscularis mucosae), the tumour is given the special name intramucosal adenocarcinoma.

Cancer cells that invade deeper in the wall are more likely to come back in the area of the original tumour (local recurrence) after treatment or to travel (metastasize) to a lymph node or distant site such as the lungs.

Tumour extension is important because it is used to determine the tumour stage (see Pathologic stage below).

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

​Lymphatics and blood vessels are channels that normal cells use to travel around the body. The presence of cancer cells within a lymphatic or blood vessel is called lymphovascular invasion and is associated with a higher risk that the tumour will travel (metastasize) to either a lymph node or a distant site 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.

 

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

  • The proximal margin - The upper portion of the esophagus.

  • The distal margin - The lower portion of the esophagus or stomach.

  • The radial margin - The tissue around the outside of the esophagus.

 

Small endoscopic resection specimens will have a deep margin and no radial margin. In the esophagus, a margin is considered ‘positive’ when there are cancer 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. Your report will also say if a precursor was seen at the margin, such as high-grade dysplasia or adenoma

 

Margins will only be described in your report after the entire tumour has been removed.

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

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

Your pathologist will carefully examine all lymph nodes 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.

 

Finding cancer cells in a lymph node is important because it 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. 

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.

 

Specific treatments are available for patients with HER2 producing tumours.

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