Lung – Adenocarcinoma

by Jason Wasserman, MD PhD FRCPC, updated on September 12, 2019

Quick facts

• Adenocarcinoma is a type of lung cancer.
• In older patients, smoking is the most common cause of lung adenocarcinoma.
• Your pathology report will include important information such as the tumour size, histologic type, and whether cancer cells are found in any lymph nodes.

In this article you will learn about:

• The normal lung
• What is adenocarcinoma?
• Immunohistochemistry
• Tumour size
• Histologic type
• Multiple tumours
• Minimally invasive adenocarcinoma
• Pleural invasion
• Invasion of organs outside of the lung
• Treatment effect
• Lymphovascular invasion
• Margins
• Lymph nodes
• Pathologic stage

The normal lung

The lungs are large organs found in our chest. They are connected to the outside of the body by hollow tubes called airways. Air travels from our mouth and nose down the airways into the lungs.

The lungs are a paired organ which means there is one on each side of the body (right and left). Each lung is divided into lobes. The right lung has three lobes, upper, middle, and lower. The left lung has only two lobes, upper and lower.

The body needs oxygen to produce energy. In the lungs, oxygen leaves the air and enters our blood. The oxygen is then delivered to the whole body by the blood. The production of energy creates carbon dioxide which is removed from the blood in the lungs.

The lungs are made up of thousands of small air filled spaces. These air filled spaces are lined by a single layer of small flat cells called pneumocytes. The tissue just below the pneumocytes is called stroma.

What is adenocarcinoma?

Adenocarcinoma is a type of lung cancer. Adenocarcinoma starts from the pneumocytes that line the inside of the air spaces. Adenocarcinoma is the most common type of lung cancer in North America.

In many cases, this tumour starts from a pre-cancerous disease called atypical adenomatous hyperplasia. The cells in atypical adenomatous hyperplasia look abnormal but they are not yet cancer cells.

Over time, atypical adenomatous hyperplasia can turn into a more serious condition called adenocarcinoma in situ. This condition is considered a non-invasive type of cancer because the abnormal cells are only seen on inner surface of the air spaces and the growth is less than 3 centimeters in size.

Invasive adenocarcinoma means the tumour cells have entered the stroma below the surface of the air space or that the tumour is larger than 3 centimeters. The movement of tumour cells from the airspace into the stroma is called invasion.
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The diagnosis of adenocarcinoma is usually made after a small sample of tissue is removed in a procedure called a biopsy or a fine needle aspiration (FNA). Surgery may then be performed to remove the entire tumour.

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.

Immunohistochemistry​

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

Adenocarcinoma usually shows the following results:

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

Why is this important? This test is used to confirm the diagnosis of adenocarcinoma. Your report may not include all of the results shown above.

Tumour size

​This is the size of the tumour measured in centimeters (cm). The size of the tumour can only be measured after the entire tumour has been removed. The tumour is measured in three dimensions but only the largest dimension may be described in your pathology report.

If some of the tumour is non-invasive, the invasive and non-invasive parts will be measured separately. In this situation, your report will include the size of the whole tumour (invasive plus non-invasive parts) and the size of just the invasive part.

Why is this important? Only the invasive part of the tumour is used to determine the tumour stage (see Pathologic stage below).

Histologic type

There are different types of adenocarcinoma in the lung and each is called a histologic type. The histologic type of your tumour can only be determined after a sample of the tumour is examined under a microscope by your pathologist. The histologic type is based on the shape and size of the cancer cells and the way the cancer cells stick together.

A tumour may be made up of just one histologic type or multiple histologic types may be seen in the same tumour. If multiple histologic types are seen, your pathology report will describe the percentage of the tumour made up by each type. The histologic type that makes up most of the tumour is called the predominant type (or predominant pattern).

The most common histologic types of adenocarcinoma in the lung are:

• Lepidic – The cancer cells in the lepidic type are seen growing along the inner lining of the air spaces. The cancer cells replace the normal pneumocytes as they grow. If the tumour is made up entirely of the lepidic type and is less than 3 centimeters in size, it is called adenocarcinoma in situ.
• Acinar – The cancer cells in the acinar type stick together to form small round groups of cells with an open space in the middle. The open space is called a lumen.
• Solid – The cancer cells in the solid type grow as one large group of cells with little space in between the cells.
• Micropapillary – The cancer cells in the micropapillary type stick together to form small groups of cells that sit inside an empty space.
• Papillary – The cancer cells in the papillary type stick together to form long finger like projections of tissue.

Why is this important? Some patterns, such as micropapillary and solid, are more likely to spread to lymph nodes or other tissues outside of the lungs. The spread of cancer cells to a lymph node or other part of the body is called metastasis.

Multiple tumours

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 cancer 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 histologic type. For example, if all of the tumours are acinar type adenocarcinoma.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 a metastasis.
2. The tumours are unrelated. This is the more likely explanation when the tumours are of different histologic types. For example, one tumour is an adenocarcinoma while the other is a squamous cell carcinoma. In this situation the tumours are considered separate primaries and not metastatic disease.​

Why is this important? Tumour nodules increase the tumour stage while metastatic disease increases the metastatic stage (see Pathologic stage below). Both are associated with worse prognosis.

Minimally invasive adenocarcinoma

A tumour is called minimally invasive if the invasive part of the tumour is no greater than 0.5 centimeters in size. Once the invasive area of the tumour passes 0.5 centimeters, the diagnosis changes to invasive adenocarcinoma (it is no longer minimally invasive).

The invasive part of the tumour is usually found next to a non-invasive area which may be larger than 0.5 centimeters. The non-invasive part is called adenocarcinoma in situ.

Why is this important? Minimally invasive adenocarcinoma is associated with very good prognosis compared to invasive adenocarcinoma. However, when a minimally invasive adenocarcinoma is found in the same lung as an invasive adenocarcinoma, the prognosis is determined by the larger tumour.

Pleural invasion

​The lungs are surrounded by a thin tissue called 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 pleura under the microscope to see if any cancer cells have passed the inner lining of the pleural. The movement of cancer cells through the inner lining of the pleural is called pleural invasion.

Why is this important? Pleural invasion increase the tumour stage (see Pathologic stage below) and is associated with worse prognosis.

Invasion of organs outside of the lung

The lung is surrounded by several organs including bones, muscles, diaphragm, heart, esophagus, and trachea. Large tumours can grow grow beyond the lung and into any of these surrounding organs.

Why is this important? Invasion into another organ increases the tumour stage (see Pathologic stage below) and is associated with worse prognosis.

Treatment effect​

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 living (viable) 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%.

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 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.

For adenocarcinoma, a margin is considered positive when there are cancer cells at the edge of the cut tissue. 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.

Why is this important? A positive margin is associated with a higher risk that the cancer will re-grow (local recurrence) 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, 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 (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.

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

​Pathologic stage

​The pathologic stage for adenocarcinoma 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.

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 adenocarcinoma

Adenocarcinoma 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.

• T1 – The tumour is 3 cm or less and there is no pleural invasion.
• T2 – The tumour is greater than 3 cm but less then 5 cm or there is pleural invasion.
• T3 – The tumour is greater than 5 cm but less then 7 cm or a separate tumour nodule is found in the same lobe of the lung or the cancer cells are seen in the outer lining of the lung, nerves outside the lung, or the lining the surrounds the heart.
• T4 – The tumour is greater than 7 cm or a separate tumour nodule is found in a different lobe of the lung on the same side or cancer cells are seen in adjacent organs such as the heart, esophagus, aorta, or trachea.

Nodal stage (pN) for adenocarcinoma

Adenocarcinoma 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 adenocarcinoma

Adenocarcinoma 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.