Squamous cell carcinoma of the lung

by Jason Wasserman MD PhD FRCPC
May 26, 2022

What is squamous cell carcinoma of the lung?

Squamous cell carcinoma is a type of lung cancer. The tumour starts from specialized squamous cells that are normally found on the inside of the airways of the lungs. These cells normally form a barrier called the epithelium which helps protect the airways from damage.

What causes squamous cell carcinoma in the lung?

The most common cause of squamous cell carcinoma in the lungs is long-term exposure to cigarette smoke.

How do pathologists make the diagnosis of squamous cell carcinoma of the lung?​

The diagnosis of squamous cell carcinoma is usually made after a small sample of tissue is removed in a procedure called a biopsy or a fine needle aspiration (FNA). The diagnosis can also be made after the entire tumour has been removed.

What does squamous cell carcinoma of the lung look like under the microscope?

When examined under the microscope, squamous cell carcinoma is usually made up of large pink cells that grow in groups called sheets or nests. However, the tumour cells in squamous cell carcinoma look different from the healthy squamous cells that normally line the inside of the airways. The tumour cells are usually larger than normal squamous cells and the nucleus of the cell which holds the genetic material is darker. Pathologists describe these cells as hyperchromatic. Tumour cells also tend to show a range of shapes and sizes which pathologists describe as pleomorphic. Numerous mitotic figures (tumour cells dividing to create new tumour cells) are also usually seen.

What other tests may be performed to confirm the diagnosis?

Your pathologist may perform a test called immunohistochemistry to confirm the diagnosis. This test helps differentiate squamous cell carcinoma from other tumours such as adenocarcinoma that can look similar under the microscope. The results will be described as positive (reactive) or negative (non-reactive).

Squamous cell carcinoma usually shows the following results:

• p40 – Positive.
• CK5 – Positive.
• TTF-1 – Negative.
• Chromogranin – Negative.
• Synaptophysin – Negative.

What happens if more than one tumour is found?

In some situations, more than one tumour is found when the lung tissue is examined under the microscope. When this happens, each tumour will be described separately in your report.

There are two possible explanations for finding more than one tumour:

1. The tumour cells from one tumour have spread to another part of the lung. This explanation is more likely when all of the tumours are of the same type. For example, all of the tumours are squamous cell carcinoma. If the tumours are on the same side as the body, the smaller tumours are called nodules. If the tumours are on different sides of the body (right and left lung), the smaller tumour is called metastasis. Tumour nodules increase the tumour stage while metastatic disease increases the metastatic stage (see Pathologic stage below). Both are associated with a worse prognosis.
2. The tumours have developed separately. This is the more likely explanation when the tumours are of different types. For example, one tumour is a squamous cell carcinoma and the other is an adenocarcinoma. In this situation, the tumours are considered separate primaries and not metastatic disease.​

What does pleural invasion mean and why is it important?

​The lungs are surrounded by a thin tissue called the pleura. The pleura has both an inner and outer lining. The inner lining touches the lung and the outer lining faces an open cavity called the pleural space. Tumours that break through the inner lining of the pleura can spread into the pleural space and from there to other parts of the body.

Your pathologist will closely examine all the sections of the pleura under the microscope to see if any tumour cells have passed the inner lining of the pleural. The movement of tumour cells through the inner lining of the pleural is called pleural invasion. Pleural invasion is important because it increases the tumour stage (see Pathologic stage below) and is associated with a worse prognosis.

Has the tumour grown into organs outside of the lung?

The lung is surrounded by several organs including bones, muscles, diaphragm, heart, esophagus, and trachea. Large tumours can grow beyond the lung and into any of these surrounding organs. Invasion into another organ is important because it increases the tumour stage (see Pathologic stage below) and is associated with a worse prognosis.

What does treatment effect​ mean?

Treatment effect is described in your report only if you received either chemotherapy or radiation therapy prior to surgery to remove the tumour. In order to determine the treatment effect, your pathologist will measure the amount of viable (living) tumour and express that number as a percentage of the original tumour. For example, if your pathologist finds 1 cm of viable tumour and the original tumour was 10 cm, the percentage of viable tumour is 10%.

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

What is a margin?

In order to remove a tumour from the lung, normal lung tissue, blood vessels, and airways all have to be cut. Any tissue that is cut when removing a tumour is called a margin and all margins are examined closely for any microscopic evidence of tumour. Margins will only be described in your report after the entire tumour has been removed.

For squamous cell carcinoma, a margin is considered positive when there are tumour cells at the edge of the cut tissue. If no tumour cells are seen at any of the cut edges of tissue, the margins are called negative. A positive margin is associated with a higher risk that the tumour will re-grow (local recurrence) in the same site after treatment.

What are lymph nodes​?

Lymph nodes are small immune organs located throughout the body. Tumour 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 tumour cells from the tumour to a lymph node is called metastasis.

Lymph nodes from the neck, chest, and lungs may be removed at the same time as the tumour. These lymph nodes are divided into areas called stations. There are 14 different stations in the neck, chest, and lungs. Your pathology report will describe the number of lymph nodes examined from each station.

Stations that may be described in your report:

• Station 1 – Lower cervical, supraclavicular, and sternal notch lymph nodes.
• Station 2 – Upper paratracheal lymph nodes.
• Station 3 – Prevascular and retrotracheal lymph nodes.
• Station 4 – Lower paratracheal lymph nodes.
• Station 5 – Subaortic lymph nodes (aortopulmonary window).
• Station 6 – Paraaortic lymph nodes (ascending aorta or phrenic).
• Station 7 – Subcarinal lymph nodes.
• Station 8 – Paraesophageal lymph nodes (below carina).
• Station 9 – Pulmonary ligament lymph nodes.
• Station 10 – Hilar lymph nodes.
• Station 11 – Interlobar lymph nodes.
• Station 12 – Lobar lymph nodes.
• Station 13 – Segmental lymph nodes.
• Station 14 – Subsegmental lymph nodes.

Your pathologist will carefully examine each lymph node for tumour cells. Lymph nodes that contain tumour cells are often called positive while those that do not contain any tumour cells are called negative. If tumour cells are found in a lymph node, the station of the positive lymph node will be described in your report.

Finding tumour cells in a lymph node increases the nodal stage (see Pathologic stage below) and is associated with a worse prognosis. The nodal stage selected will depend on where the lymph node with tumour cells was located (the station).

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

​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 a worse prognosis.

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

Squamous cell carcinoma is given a tumour stage between 1 and 4 based on the size of the tumour, the number of tumours found in the tissue examined, and whether the tumour has broken through the pleural or has spread to organs around the lungs.

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

Squamous cell carcinoma is given a nodal stage between 0 and 3 based on the presence or absence of cancer cells in a lymph node and the location of the lymph nodes that contain tumour cells.

• NX – No lymph nodes were sent for pathologic examination.
• N0 – No tumour cells were found in any of the lymph nodes examine
• N1 – Tumourcells were found in at least one lymph node from inside the lung or around the large airways leading into the lung. This stage includes stations 10 through 14.
• N2 – Tumour cells were found in at least one lymph node from the tissue in the middle of the chest and around the large airways. This stage includes stations 7 through 9.
• N3 – Tumour cells were found in the neck or in any lymph nodes on the side of the body opposite (contralateral) to the tumour. This stage includes stations 1 through 6.

Metastatic stage (pM) for squamous cell carcinoma of the lung

Squamous cell carcinoma is given a metastatic stage of 0 or 1 based on the presence of tumour cells in the lung on the opposite side of the body or at a distant body site (for example the brain). The metastatic stage can only be determined if tissue from the opposite lung or distant site is sent for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as pMX.