Squamous cell carcinoma

This article was last reviewed and updated on November 20, 2019

by Jason Wasserman, MD PhD FRCPC

Quick facts:

• Squamous cell carcinoma is a type of cancer of the esophagus.
• It starts from the cells that line the inside of the esophagus.
• Your pathology report for squamous cell carcinoma includes important information such as the tumour size and the distance the cancer cells have traveled into the wall of the esophagus and surrounding tissues.

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 esophagus is made up of six layers of tissue:

• Epithelium – The epithelium is 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.

What is squamous cell carcinoma?

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.

Squamous cell carcinoma 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.

Symptoms of squamous cell carcinoma in the esophagus include difficultly or pain when swallowing food. The symptoms are worse initially with solids but progress to both solids and liquids.

The diagnosis of squamous cell carcinoma 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.

Histologic grade

Pathologists use the word grade to describe how different the cancer cells in squamous cell carcinoma look compared the squamous cells normally found in the esophagus.

Pathologists divide the grade into three categories based on how the cancer cells look when examined under the microscope.

1. Well differentiated – The cancer cells look very similar to the normal squamous cells.
2. Moderately differentiated – The cancer cells are clearly abnormal but still share many features with normal squamous cells.
3. Poorly differentiated – The cancer cells look very different than normal squamous cells. Special tests such as immunohistochemistry may need to be performed to prove that the cancer cells are squamous cells.

Why is this important? Grade is important because poorly differentiated tumours are more likely to spread to other parts of the body and to re-grow after treatment.

Tumour site

The esophagus is a long tube that starts at the back of your throat and ends at the top of the stomach. The normal esophagus is divided into three parts:

1. Cervical esophagus – This is the first part of the esophagus. It starts at the back of the throat and ends near the bottom of your neck.
2. Thoracic esophagus – This is the second part of the esophagus. It starts at the bottom of your neck and ends where the esophagus meets the stomach.
3. Gastroesophageal junction – This is the connection between the esophagus and the stomach.

In your report, tumour  site refers to the part of the esophagus or stomach involved by the tumour. Most squamous cell carcinomas start in the cervical or thoracic part of the esophagus.

Tumour size
This is the size of the tumour. Tumour size will only be described in your report after the entire tumour has been removed. The tumour is usually measured in three dimensions but only the largest dimension is described in your report. For example, if the tumour measures 4.0 cm by 2.0 cm by 1.5 cm, your report will describe the tumour as being 4.0 cm.

Tumour extension

​The esophagus is a tube and the wall of the tube is made up of six different layers of tissue (see The esophagus above). Squamous cell carcinoma 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.

​Perineural invasion

Nerves are like long wires made up of groups of cells called neurons. Nerves send information (such as temperature, pressure, and pain) between your brain and your body. Perineural invasion means that cancer cells were seen attached to a nerve.

Why is this important? Cancer cells that have attached to a nerve can use the nerve to travel into tissue outside of the original tumour. This increases the risk that the tumour will re-grow in the same area of the body (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.

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).

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 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.

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) for squamous cell carcinoma of the esophagus

Squamous cell carcinoma 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.
• T1 – The cancer cells have broken out of the epithelium and have entered the lamina propria, muscularis mucosae, or submucosa.
• T2 – The cancer cells are in the muscularis propria of the esophagus.
• T3 – The cancer cells have gone through the entire wall and is on the outer surface of the esophagus.
• T4 – The tumour has gone 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 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) for squamous cell carcinoma of the esophagus

Squamous cell carcinoma 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.