Squamous cell carcinoma of the esophagus

by Jason Wasserman MD PhD FRCPC
May 24, 2023

What is squamous cell carcinoma of the esophagus?

Squamous cell carcinoma is a type of esophageal cancer. It starts from specialized squamous cells that cover the inside of the esophagus.

What causes squamous cell carcinoma in the esophagus?

Squamous cell carcinoma in the esophagus is associated with both long-term alcohol use and smoking although a variety of injuries and chemicals can also cause this kind of cancer.

What are the symptoms of squamous cell carcinoma in the esophagus?

Symptoms of squamous cell carcinoma in the esophagus include difficulty or pain when swallowing food. This is sometimes described as the sensation of food getting “stuck” after swallowing. The symptoms are worse initially with solids but progress to both solids and liquids.

How do pathologists make the diagnosis of squamous cell carcinoma in the esophagus?

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.

What does it mean if squamous cell carcinoma of the esophagus is described as well, moderately, or poorly differentiated?

Pathologists divide squamous cell carcinoma of the esophagus into three grades – well, moderately, and poorly differentiated – based on how much the tumour cells look like normal squamous cells when examined under the microscope. The grade is important because higher-grade tumours (moderately and poorly differentiated tumours) behave in a more aggressive manner and are more likely to spread to other parts of the body.

Squamous cell carcinoma of the esophagus is graded as follows:

1. Well differentiated squamous cell carcinoma of the esophagus – A well differentiated tumour (also known as grade 1) is made up of tumour cells that look almost the same as normal squamous cells.
2. Moderately differentiated squamous cell carcinoma of the esophagus – A moderately differentiated tumour (also known as grade 2) is made up of tumour cells that clearly look different from normal squamous cells, however, they can still be recognized as squamous cells.
3. Poorly differentiated squamous cell carcinoma of the esophagus – A poorly differentiated tumour (also known as grade 3) is made up of tumour cells that look very little like normal squamous cells. These cells can look so abnormal that your pathologist may need to order an additional test such as immunohistochemistry to confirm the diagnosis.

What does invasion mean and why is the level of invasion important?

Pathologists use the word invasion to describe the spread of tumour cells from the inside of the esophagus into the surrounding tissues. All squamous cell carcinomas in the esophagus start in a thin layer of tissue on the inside of the esophagus called the epithelium. Below the epithelium is another thin layer of supporting tissue called the lamina propria. Together the epithelium and lamina propria is called the mucosa. The layers of tissue below the mucosa include the submucosa, muscularis propria, and adventitia. As the tumour grows the cells can spread into these layers. Eventually, the tumour cells can break through the outside surface of the esophagus and spread directly into nearby organs and tissues.

Pathologists use special terms for tumours that are only seen near the inside surface of the esophagus. High grade dysplasia is a term used to describe a tumour that only involves the epithelium. Intramucosal is a term used to describe a tumour that involves the epithelium, lamina propria, or muscularis mucosa but does not extend into the submucosa.

The level of invasion is the deepest point of invasion and it can only be measured after the tumour is examined under the microscope by a pathologist. The level of invasion is important because tumours that invade deeper into the wall of the esophagus are more likely to spread to other parts of the body. The level of invasion is also used to determine the pathologic tumour stage (pT).

​What does perineural invasion mean?

Perineural invasion is a term pathologists use to describe cancer cells attached to or inside a nerve. A similar term, intraneural invasion, is used to describe cancer cells inside a nerve. Nerves are like long wires made up of groups of cells called neurons. Nerves are found all over the body and they are responsible for sending information (such as temperature, pressure, and pain) between your body and your brain. Perineural invasion is important because the cancer cells can use the nerve to spread into surrounding organs and tissues. This increases the risk that the tumour will regrow after surgery. If perineural invasion is seen, it will be included in your report.

What does lymphovascular invasion mean?

Lymphovascular invasion means that cancer cells were seen inside a blood vessel or lymphatic vessel. Blood vessels are long thin tubes that carry blood around the body. Lymphatic vessels are similar to small blood vessels except that they carry a fluid called lymph instead of blood. The lymphatic vessels connect with small immune organs called lymph nodes that are found throughout the body. Lymphovascular invasion is important because cancer cells can use blood vessels or lymphatic vessels to spread to other parts of the body such as lymph nodes or the lungs. If lymphovascular invasion is seen, it will be included in your report.

Were lymph nodes examined and did any contain cancer cells?

Lymph nodes are small immune organs found throughout the body. Cancer cells can spread from a tumour to lymph nodes through small vessels called lymphatics. Lymph nodes are not always removed at the same time as the tumour. However, when lymph nodes are removed, they will be examined under a microscope and the results will be described in your report.

Cancer cells typically spread first to lymph nodes close to the tumour although lymph nodes far away from the tumour can also be involved. For this reason, the first lymph nodes removed are usually close to the tumour. Lymph nodes further away from the tumour are only typically removed if they are enlarged and there is a high clinical suspicion that there may be cancer cells in the lymph node. Most reports will include the total number of lymph nodes examined, where in the body the lymph nodes were found, and the number (if any) that contain cancer cells. If cancer cells were seen in a lymph node, the size of the largest group of cancer cells (often described as “focus” or “deposit”) will also be included.

Why is the examination of lymph nodes important?

The examination of lymph nodes is important for two reasons. First, this information is used to determine the pathologic nodal stage (pN). Second, finding cancer cells in a lymph node increases the risk that cancer cells will be found in other parts of the body in the future. As a result, your doctor will use this information when deciding if additional treatment such as chemotherapy, radiation therapy, or immunotherapy is required.

What does it mean if a lymph node is described as positive?

Pathologists often use the term “positive” to describe a lymph node that contains cancer cells. For example, a lymph node that contains cancer cells may be called “positive for malignancy” or “positive for metastatic carcinoma”.

What does it mean if a lymph node is described as negative?

Pathologists often use the term “negative” to describe a lymph node that does not contain any cancer cells. For example, a lymph node that does not contain cancer cells may be called “negative for malignancy” or “negative for metastatic carcinoma”.

What does extranodal extension mean?

All lymph nodes are surrounded by a thin layer of tissue called a capsule. Extranodal extension means that cancer cells within the lymph node have broken through the capsule and have spread into the tissue outside of the lymph node. Extranodal extension is important because it increases the risk that the tumour will regrow in the same location after surgery. For some types of cancer, extranodal extension is also a reason to consider additional treatment such as chemotherapy or radiation therapy.

What is a margin?

​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 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 the 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.

What is the pathologic stage (pTNM) for squamous cell carcinoma of the esophagus?

​The pathologic stage for squamous cell carcinoma of the esophagus 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 a more advanced disease and a worse prognosis.

Tumour stage (pT) for squamous cell carcinoma of the esophagus

Squamous cell carcinoma is given a tumour stage between 1 and 4 based on how far the tumour cells have spread from the epithelium on the inner surface of the esophagus into the wall of the esophagus or surrounding tissues.​

• Tis – The tumour 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.
• T1 – The tumour cells have spread into the lamina propria, muscularis mucosae, or submucosa.
• T2 – The tumour cells have spread into the muscularis propria of the esophagus.
• T3 – The tumour cells have spread through the wall and are seen on the outer surface of the esophagus.
• T4 – The tumour extended into surrounding organs or tissues such as the lungs or aorta.

Nodal stage (pN) for squamous cell carcinoma of the esophagus

Squamous cell carcinoma is given a nodal stage between 0 and 3 based on finding tumour cells in a lymph node and the number of lymph nodes involved.

• N0 – No tumour cells are seen in any lymph nodes examined.
• N1 – Tumour cells are seen in one or two lymph nodes.
• N2 – Tumour cells are seen in three to six lymph nodes.
• N3 – Tumour cells are seen in more than 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) for squamous cell carcinoma of the esophagus

Squamous cell carcinoma is given a metastatic stage of 0 or 1 based on the presence of tumour 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.