Adenocarcinoma of the lung

by Jason Wasserman MD PhD FRCPC
May 26, 2022

What is adenocarcinoma of the lung?

Adenocarcinoma is a type of lung cancer. Adenocarcinoma starts from specialized cells called pneumocytes that line the inside of the air spaces called alveoli in the lungs. It is the most common type of lung cancer in North America.

What causes adenocarcinoma in the lung?

The leading cause of adenocarcinoma is tobacco smoking. Other less common causes include radon exposure, occupational agents, and outdoor air pollution.

What diseases lead to adenocarcinoma of the lung?

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

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

Adenocarcinoma in situ becomes invasive adenocarcinoma if the cancer cells spread into the stroma below the surface of the air space or if the tumour grows to be larger than 3 centimetres in size.

How do pathologists make the diagnosis of adenocarcinoma in the lung?

The initial diagnosis of adenocarcinoma in the lung 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. The type of surgery performed to remove the tumour will depend on the size of the tumour and its location in your lung. A wedge resection is usually performed to remove small tumours and those near the outside of the lungs. Lobectomies and pneumonectomies are performed for large tumours or those that are near the centre of the lungs.

After the entire tumour is removed, it will be sent to a pathologist for examination under the microscope. Your final pathology report will include important information such as the tumour size, histologic type, and whether the tumour cells have spread into other tissues such as the pleural or lymph nodes. This information will be explained in greater detail in the sections below.

What other tests are performed to confirm the diagnosis of adenocarcinoma?

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.

What are the subtypes of adenocarcinoma in the lung?

Pathologists divide adenocarcinoma of the lung into different subtypes based on the way the cells stick together as the tumour grows. Pathologists call this the pattern of growth and the most common patterns of growth are called lepidic, solid, acinar, papillary, and micropapillary.

A tumour may show just one pattern of growth or multiple patterns of growth may be seen in the same tumour. If multiple patterns of growth are seen, most pathologists will describe the percentage of the tumour made up by each pattern. The histologic type that makes up most of the tumour is called the predominant pattern.

The pattern of growth is important because 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.

Common patterns of growth include:

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

What happens if multiple tumours are 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 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 metastasis.
2. The tumours have developed separately. 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.​

What is minimally invasive adenocarcinoma?

A tumour is called minimally invasive if the invasive part of the tumour is no greater than 0.5 centimetres in size. Once the invasive area of the tumour passes 0.5 centimetres, 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 centimetres. The non-invasive part is called adenocarcinoma in situ.

Minimally invasive adenocarcinoma is associated with a 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.

What does pleural invasion mean?

​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. For this reason, your pathologist will closely examine all the sections of the 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. Pleural invasion increases the tumour stage (see Pathologic stage below) and is associated with a worse prognosis.

Has the tumour spread 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 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 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%.

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 lymphatic channels. Tumour cells can use blood vessels and lymphatics to travel away from the tumour to other parts of the body. The movement of tumour cells from the tumour to another part of the body is called metastasis.

Before tumour cells can metastasize, they need to enter a blood vessel or lymphatic. This is called lymphovascular invasion. Lymphovascular invasion increases the risk that tumour cells will be found in a lymph node or a distant part of the body such as the lungs.

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.

For adenocarcinoma of the lung, 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 cancer 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. 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 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 adenocarcinoma of the lung?

​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 a worse prognosis.

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.

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.