Squamous cell carcinoma of the esophagus

by Jason Wasserman MD PhD FRCPC
May 9, 2022

What is squamous cell carcinoma of the esophagus?

Squamous cell carcinoma is a type of esophageal cancer. Squamous cell carcinoma starts on the inside of the esophagus from the squamous cells in the epithelium.

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 squamous cell carcinoma in the esophagus.

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?

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. This report will confirm or revise the original diagnosis and provide additional important information such tumour size, extension, margins, and spread of tumour cells to lymph nodes. This information is used to determine the cancer stage and to decide if additional treatment is required.

How do pathologists grade squamous cell carcinoma of the esophagus?

Pathologists use the term differentiated to divide squamous cell carcinoma of the esophagus into three grades – well-differentiated, moderately differentiated, and poorly differentiated. The grade is based on how much the tumour cells look like normal squamous cells. A well-differentiated tumour (grade 1) is made up of tumour cells that look almost the same as normal squamous cells. A moderately differentiated tumour (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. A poorly differentiated tumour (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. The grade is important because less differentiated tumours (moderately and poorly differentiated tumours) behave in a more aggressive manner and are more likely to spread to other parts of the body.

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?

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 a term pathologists use to describe tumour cells attached to a nerve. Perineural invasion is important because tumour cells that have become attached to a nerve can grow along the nerve and into surrounding tissues. This increases the risk that the tumour will re-grow after treatment.

What does lymphovascular invasion mean?

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. The term lymphovascular invasion is used to describe tumour cells that are found inside a blood vessel or lymphatic channel. Lymphovascular invasion is important because once the tumour cells are inside a blood vessel or lymphatic channel they are able to metastasize (spread) to other parts of the body such as lymph nodes or the lungs.

What are 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 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).

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 does treatment effect mean?

​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 effects.​

How do pathologists determine the pathologic stage (pTNM) for squamous cell carcinoma of the esophagus?

​The pathologic stage for squamous cell carcinoma 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.

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 of the 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 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) 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.