Adenocarcinoma of the lung

by Jason Wasserman MD PhD FRCPC
September 23, 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 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. 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 pathologic tumour stage (pT) 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?​

Lymphovascular invasion means that cancer cells were seen inside of a blood vessel or lymphatic vessel. Blood vessels are long thin tubes that carry blood around the body. Lymphatic vessels are similar to small blood vessels except that they carry a fluid called lymph instead of blood. The lymphatic vessels connect with small immune organs called lymph nodes that are found throughout the body. Lymphovascular invasion is important because cancer cells can use blood vessels or lymphatic vessels to spread to other parts of the body such as lymph nodes or the liver.

What is a margin?

​In pathology, a margin is the edge of a tissue that is cut when removing a tumour from the body. The margins described in a pathology report are very important because they tell you if the entire tumour was removed or if some of the tumour was left behind. The margin status will determine what (if any) additional treatment you may require.

Most pathology reports only describe margins after a surgical procedure called an excision or resection has been performed for the purpose of removing the entire tumour. For this reason, margins are not usually described after a procedure called a biopsy is performed for the purpose of removing only part of the tumour. The number of margins described in a pathology report depends on the types of tissues removed and the location of the tumour. The size of the margin (the amount of normal tissue between the tumour and the cut edge) depends on the type of tumour being removed and the location of the tumour.

Pathologists carefully examine the margins to look for tumour cells at the cut edge of the tissue. If tumour cells are seen at the cut edge of the tissue, the margin will be described as positive. If no tumour cells are seen at the cut edge of the tissue, a margin will be described as negative. Even if all of the margins are negative, some pathology reports will also provide a measurement of the closest tumour cells to the cut edge of the tissue.

A positive (or very close) margin is important because it means that tumour cells may have been left behind in your body when the tumour was surgically removed. For this reason, patients who have a positive margin may be offered another surgery to remove the rest of the tumour or radiation therapy to the area of the body with the positive margin. The decision to offer additional treatment and the type of treatment options offered will depend on a variety of factors including the type of tumour removed and the area of the body involved. For example, additional treatment may not be necessary for a benign (non-cancerous) type of tumour but may be strongly advised for a malignant (cancerous) type of tumour.

Were lymph nodes examined and did any contain cancer cells?

Lymph nodes are small immune organs found throughout the body. Cancer cells can spread from a tumour to lymph nodes through small vessels called lymphatics. For this reason, lymph nodes are commonly removed and examined under a microscope to look for cancer cells. The movement of cancer cells from the tumour to another part of the body such as 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 (see picture below).

If any lymph nodes were removed from your body, they will be examined under the microscope by a pathologist and the results of this examination will be described in your report. Most reports will include the total number of lymph nodes examined, where in the body the lymph nodes were found, and the number (if any) that contain cancer cells. If cancer cells were seen in a lymph node, the size of the largest group of cancer cells (often described as “focus” or “deposit”) will also be included.

The examination of lymph nodes is important for two reasons. First, this information is used to determine the pathologic nodal stage (pN). Second, finding cancer cells in a lymph node increases the risk that cancer cells will be found in other parts of the body in the future. As a result, your doctor will use this information when deciding if additional treatment such as chemotherapy, radiation therapy, or immunotherapy is required.

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.

What is 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 of the lung 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 of the lung 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 of the lung 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.