Adenocarcinoma of the esophagus

What is adenocarcinoma of the esophagus?

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

The 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 stomach is filled with a strong acid that helps your body break down food. The inner surface of the esophagus is lined by specialized squamous cells that form a barrier to protect the inside of the esophagus. This thin tissue barrier is called the epithelium.

normal esophagus histology

What causes adenocarcinoma of the esophagus?

Certain conditions, such as long-standing acid reflux disease cause the squamous cells that line the inside of the esophagus to be replaced by cells that are normally found in the small intestine. These intestinal cells are designed to protect tissue from the strong acids in the stomach. The change from squamous epithelium to intestinal epithelium is an example of intestinal metaplasia.

When intestinal metaplasia happens in the esophagus it is given the special name Barrett’s esophagus. Most patients with adenocarcinoma of the esophagus have had Barrett’s esophagus for many years. For this reason, Barrett’s esophagus is considered a pre-cancerous condition that can lead to adenocarcinoma.

How do pathologists make this diagnosis?

The diagnosis is usually made after a small piece of the tumour is removed in a procedure called a biopsy. The tissue is sent to a pathologist for examination under a microscope. A special test called immunohistochemistry may be performed to confirm the diagnosis. Most patients are then offered surgery to remove the tumour entirely. Some patients may be offered radiation or chemotherapy before or after the tumour is removed.

Once removed, the entire tumour will be sent to a pathologist who will examine parts of it under the microscope. Additional information such as the tumour size and spread of tumour cells to lymph nodes will be provided in the final pathology report.

esophagus adenocarcinoma

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 that looks like small bowel, 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.

  • Well differentiated – More than 95% of the tumour is made up of glands.
  • Moderately differentiated – 50 to 95% of the tumour is made up of glands.
  • Poorly differentiated – Less than 50% of the tumour is made up of glands.
  • Undifferentiated – There are no glands seen anywhere in the tumour.

Grade is important because poorly differentiated and undifferentiated tumours are more likely to spread to other parts of the body and are associated with a worse overall prognosis.

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.

Your pathologist may 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.

One out of every five cases of esophageal cancers produce extra HER2 and 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.

What to look for in your report after the tumour is removed

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 the greatest dimension.

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.

Esophageal and gastric tumours are treated differently and have different prognoses. Talk to your doctor about the location of your tumour and the treatment options available.

Tumour extension

Adenocarcinoma starts in the epithelium on the inner surface of the esophagus. Tumour extension describes how far the cancer cells have spread from the epithelium into the layers of tissue below. The movement of cancer cells from the epithelium into the tissue below is called invasion.

Most pathology reports describe tumour extension as follows:

  • 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.

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 to a distant site such as the lungs. The movement of cancer cells to another part of the body is called metastasis.

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. Perineural invasion is important because it is associated with a higher risk that the tumour will come back in the same area of the body (local recurrence) after treatment.

perineural invasion

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.

lymphovascular invasion

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 is important because it 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.

Margin

For esophagectomy specimens where an entire segment of the 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. A positive margin is associated with a higher risk that the tumour will re-grow in the same site after treatment.

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 metastasis.

Lymph node

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.

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).

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 a worse prognosis.

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 than six lymph nodes.
  • NX – No lymph nodes were sent to the pathologist for examination.​

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.

by Jason  Wasserman, MD PhD FRCPC (updated July 28, 2021)
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