Small cell carcinoma of the lung

What is small cell carcinoma?

Small cell carcinoma is a type of lung cancer. It is made up of neuroendocrine cells that are normally found in the lungs. The tumour often starts in the central portion of the lung, closest to the larger airways and the heart. As a result, when these cancers grow and start to invade, they can cause narrowing of the airways leading to symptoms of cough and trouble breathing.

Small cell carcinoma is considered a very aggressive type of cancer and the tumour cells have often spread to other parts of the body by the time a diagnosis is made. The movement of tumour cells to another part of the body is called metastasis.

Because small cell carcinoma is made up of neuroendocrine cells, the tumour can make and release hormones that can cause patients to have bloodwork abnormalities such as high calcium or low sodium, although these bloodwork changes also have many other causes aside from cancer.

The lungs

When you breathe, air enters your body through your mouth and nose and travels down airways into your lungs. You have two lungs, one on the right side of your chest and one on the left. Inside the lungs, oxygen enters the blood and carbon dioxide is removed from the body. As the airways enter the lungs they split into smaller and smaller airways, called bronchioles, ultimately ending in air-filled spaces called alveoli.

The alveoli are extremely small cup-shaped air-filled spaces surrounded by thin walls, often referred to as septa, which are lined by flat cells called pneumocytes. There are two types of pneumocytes. Type 1 pneumocytes are small and flat. Type 2 pneumocytes are larger and shaped more like a cube. The alveoli are surrounded by a fine network of blood vessels called capillaries which carry blood in and out of the lungs.

Normal lung

Neuroendocrine cells in the lungs

Neuroendocrine cells are specialized cells that behave in many ways like nerve cells but also make hormones like endocrine cells. In the lung, neuroendocrine cells are normally found in the walls of the airways. Scientists believe these cells play a role as airway sensors and regulate inflammation within the lung through their hormonal effects.

What causes small cell carcinoma?

These cancers develop when cells are damaged (often by the chemicals in cigarette smoke) and start to grow abnormally. The most common cause of this damage is cigarette smoke.

How is small cell carcinoma diagnosed?

The diagnosis of small 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 biopsy or FNA may be performed on the lung or another body site such as a lymph node.

Under the microscope, the tumour cells in small cell carcinoma are smaller than normal cells because they have less material in their cytoplasm (cell body). This also makes the cells look dark blue. The chromatin (genetic material) inside the nucleus of the cell is often described as fine or uniform. Large clumps of genetic material called nucleoli are usually not seen.

Small cell carcinoma

The tumour cells in small cell carcinoma are constantly dividing to create new tumour cells. This process is called mitosis and a cell that is actively dividing is called a mitotic figure. Pathologists often describe these tumours as having a very high rate of cell proliferation.

Your pathologist may perform a test called immunohistochemistry to confirm the diagnosis. The results will be described as positive (reactive) or negative (non-reactive).

Small cell carcinoma usually shows the following results:

  • Chromogranin – Positive.
  • Synaptophysin – Positive.
  • CD56 – Positive.
  • TTF-1 – Positive.

These tests are used to confirm the diagnosis of small cell carcinoma. Your report may not include all the results shown above. In addition, since small cell carcinoma shows a high rate of cell division, the Ki-67 index (a type of immunohistochemistry that highlights dividing cells) is often reported as high.

Small cell carcinoma grows very quickly and cancer cells have often spread to other parts of the body by the time a diagnosis is made. For this reason, most patients will not undergo surgery to remove the tumour in the lung. However, in some cases of small localized tumours, surgery may be performed to remove the entire tumour.

If you underwent surgery to remove the tumour from your lung, you may see the name of the procedure in your pathology report. The name will depend on the amount of tissue removed.

Procedure names include:

  • Wedge resection – In this procedure, the tumour is removed with only a small amount of normal lung around it.
  • Lobectomy – In this procedure, the entire lobe of the lung is removed along with the tumour.
  • Pneumonectomy – In this procedure, the entire lung on one side of the body is removed along with the tumour.


When surgery is performed to remove a tumour from the lungs, 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.

For small cell carcinoma, a margin is considered positive when there are cancer cells at the edge of the cut tissue. A positive margin is associated with a higher risk that the tumour will re-grow (local recurrence) in the same site after treatment. If no cancer cells are seen at any of the cut edges of tissue, the margins are called negative. Margins will only be described in your report after the entire tumour has been removed.


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. The movement of cancer 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.

Lymph node stations

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 (aorto-pulmonary 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 cancer cells. Lymph nodes that contain cancer cells are often called positive while those that do not contain any cancer cells are called negative. If cancer cells are found in a lymph node, the station of the positive lymph node will be described in your report.

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


​Small cell lung carcinoma may be staged using a two-part staging system.

  1. Limited stage means the cancer is found only on one side of the chest – either in part of one lung or in lymph nodes on the same side as the tumour. This stage can be treated with radiation to one side of the body only.
  2. Extensive stage means the cancer has spread to the other lung, to lymph nodes on the other side of the chest, or to other parts of the body such as the liver, brain, or bone. This stage also includes cases where cancer has spread to fluid around the lung or heart. Most people with small cell lung carcinoma have extensive-stage disease at diagnosis because this type of cancer spreads early and quickly and often does not cause symptoms early on.

Small cell lung cancer can also be staged using the TNM system. 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.

The pathologic stage will only be described in your report after the entire tumour has been removed. It will not be included after a biopsy.

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

Small 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.

Lung staging

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

Small 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 cancer cells.

  • NX – No lymph nodes were sent for pathologic examination.
  • N0 – No cancer cells were found in any of the lymph nodes examine
  • N1 – Cancer cells 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 -Cancer 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 – Cancer 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 small cell carcinoma of the lung

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

by Katherina Baranova MD and Matt Cecchini MD FRCPC (updated August 3, 2021)
A+ A A-