Atypical carcinoid tumour of the lung

What is an atypical carcinoid tumour?

An atypical carcinoid tumour is a type of cancer made up of specialized neuroendocrine cells. This type of tumour can start in the lungs or in any other location where neuroendocrine cells are normally found.

In the lung, these tumours start from the neuroendocrine cells normally found in the walls of the airways and are often located in the central part of the lung near the heart. Since they are closely associated with airways, they can block and lead to the collapse of the lung. They can also invade through the airway which can lead to coughing up blood.

Compared to other types of cancer, atypical carcinoid tumours are slow-growing but can spread away from the lungs to other parts of the body. The movement of cancer cells to another part of the body is called metastasis.

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.

Normal lung

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. They allow the lungs to exchange oxygen in the air for carbon dioxide in the blood. Type 2 pneumocytes are larger and shaped more like a cube. They produce a chemical called surfactant that helps the lung tissue to expand and contract. The alveoli are surrounded by a fine network of blood vessels called capillaries which carry blood in and out of the lungs.

Neuroendocrine cells in the lungs

Neuroendocrine cells are specialized cells that communicate with the nervous system and with other cells by producing hormones. 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 that they send signals to cells in the immune system when problems are detected in the lungs. These signals can result in a process called inflammation.

Carcinoid syndrome

Because atypical carcinoid tumours are made up of neuroendocrine cells, the tumour can make and release hormones such as serotonin. The extra serotonin can cause symptoms such as flushing and diarrhea.  Doctors describe these symptoms as carcinoid syndrome. These symptoms atypically only occur if the tumour has spread to the liver.

How is an atypical carcinoid tumour diagnosed?

The diagnosis of atypical carcinoid is usually made after a small sample of tissue is removed from the lung in a procedure called a biopsy or a fine needle aspiration (FNA). However, imaging can also lead a doctor to suspect carcinoid. When examined under the microscope, atypical carcinoid tumours are made up of cells that all look very similar. Pathologists often describe the nucleus of the cell as “salt and pepper” because the chromatin or genetic material looks like small dark dots on a white background.

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

Atypical carcinoid tumours usually show the following results:

Marker Result
Chromogranin Positive (reactive)
Synaptophysin Positive (reactive)
CD56 Positive (reactive)
TTF-1 Usually positive (reactive) but can be negative (non-reactive)

 

These tests are used to confirm the diagnosis of an atypical carcinoid tumour. Your report may not include all of the results shown above. In addition, since atypical carcinoid tumours show a slow rate of cell division, the Ki-67 proliferation index (a type of immunohistochemistry that highlights dividing cells) is often reported as low.

Surgery may be performed to remove the entire tumour and you may see the name of the procedure performed 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.

Typical vs atypical carcinoid tumour

To make the diagnosis of an atypical carcinoid tumour, the number of mitotic figures (dividing tumour cells) is between 2 and 10 over an area of 2 square millimetres or 10 high powered fields of magnification. There can also be evidence for a type of cell death called necrosis.

Tumours with less than 2 mitotic figures and without necrosis are classified as typical carcinoid tumours. Your pathologist will make this distinction because atypical carcinoid tumours have a higher risk of spreading to other parts of your body or growing back in the lung after treatment.

​Margins

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.

Margin

If no cancer cells are seen at any of the cut edges of tissue, the margins are called negative. 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 cancer will re-grow (local recurrence) in the same site after treatment.

What is a carcinoid tumourlet?

A group of neuroendocrine cells in the lung that measures less than 5 millimetres in size is called a carcinoid tumourlet. In addition to the size, a group of neuroendocrine cells can only be called a tumourlet if the cells do not show any abnormal features such as an increased number of dividing cells or cell death. A dividing cell is called a mitotic figure because it is undergoing a process called mitosis which creates two new cells.

Most pathologists consider carcinoid tumourlets to be a benign (non-cancerous) overgrowth of neuroendocrine cells and not a type of cancer. Carcinoid tumourlets can be found in the lung tissue surrounding an atypical carcinoid tumour or in lung tissue removed for other reasons.

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

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 Pathologic stage 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).

Pathologic stage

​Atypical carcinoid tumours are 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 atypical carcinoid tumour

Atypical carcinoid 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 atypical carcinoid tumour

Atypical carcinoid 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 atypical carcinoid tumour

Atypical carcinoid 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 June 24, 2021)
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