Adenocarcinoma of the lung

by Jason Wasserman MD PhD FRCPC and Zuzanna Gorski MD
March 27, 2024

Adenocarcinoma is a type of non-small cell lung cancer (NSCLC) and the most common type of lung cancer accounting for 40% of all cases in North America. It starts from specialized cells called pneumocytes that line the inside of small air spaces called alveoli in the lungs.

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 are the symptoms of adenocarcinoma in the lung?

Symptoms of adenocarcinoma of the lung include persistent or worsening cough, coughing up blood, chest pain, and shortness of breath. Tumours that have spread to other parts of the body may cause additional symptoms depending on the location in the body. For example, tumours that spread to bones may cause bone pain and can cause the bone to break. Doctors describe this as a pathologic fracture.

What conditions are associated with 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 is this diagnosis made?

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.

Histologic types of adenocarcinoma of the lung

Adenocarcinoma of the lung is classified into histologic types based on its pattern of growth, the way the cancer cells stick together, and the structures it forms. The most common histologic types of adenocarcinoma are lepidic, solid, acinar, papillary, and micropapillary.

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

Lepidic pattern

Lepidic-type adenocarcinoma of the lung means that cancer cells are seen growing along the inner lining of the air spaces called alveoli. The cancer cells replace the normal pneumocytes as they grow. This is the most common histologic type of adenocarcinoma. If the tumour is less than 3 cm in size and shows an entirely lepidic pattern of growth, it is called adenocarcinoma in situ.

Acinar pattern

Acinar-type adenocarcinoma of the lung means that the cancer cells form small, round groups of cells with an open space in the middle, called a lumen. This is the second most common histologic type of adenocarcinoma.

Solid pattern

Solid-type adenocarcinoma of the lung means that the cancer cells form large groups with little space between them. This type of adenocarcinoma is more aggressive than the lepidic and acinar types and more likely to metastasize (spread) to lymph nodes.

Papillary pattern

Papillary-type adenocarcinoma of the lung means that the cancer cells stick together to form long finger-like projections of tissue called papilla. The papillary type of adenocarcinoma tends to be more aggressive than lepidic predominant tumours but is less aggressive than the solid or micropapillary types.

Micropapillary pattern

Micropapillary-type adenocarcinoma of the lung means that the cancer cells stick together to form small groups of cells that sit inside a space. This aggressive type of cancer frequently metastasizes (spreads) to lymph nodes and other parts of the lungs.

Tumour grade

Adenocarcinoma of the lung is divided into three grades (well differentiated moderately differentiated, and poorly differentiated) based on a combination of the predominant (most common) histologic type (pattern of growth) and the worst (or most aggressive) histologic type. The tumour grade is important because it is a good predictor of how the tumour will respond to treatment. This grading scheme is only applied to nonmucinous adenocarcinoma of the lung (tumours not producing large amounts of mucin).

Grading scheme for adenocarcinoma of the lung:

• Well differentiated: A mostly or entirely lepidic-type tumour with less than 20% solid or micropapillary growth.
• Moderately differentiated: A mostly or entirely acinar-type or papillary-type tumour with less than 20% solid or micropapillary growth.
• Poorly differentiated: A tumour with greater than 20% solid or micropapillary growth or with areas made up of complex glands or single cells.

Immunohistochemistry

Immunohistochemistry (IHC) is a test that allows pathologists to identify specific types of cells based on the chemicals, typically proteins, those cells are making. Because different types of cells express different IHC markers, pathologists can use this test to distinguish between different types of cancers.

When IHC is performed, adenocarcinoma of the lung usually shows the following results:

• TTF-1 – Positive in 80% of tumours.
• p40 – Negative.
• CK5 – Negative.
• Chromogranin – Negative.
• Synaptophysin – Negative.

Genetic changes found in adenocarcinoma carcinoma of the lung

Genetic changes commonly found in adenocarcinoma of the lung include mutations in genes such as EGFR, KRAS, and ALK. Pathologists test for these and other genetic alterations using techniques such as next-generation sequencing (NGS), immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH). Identifying specific genetic mutations is important for selecting targeted therapies.

Spread through air spaces

Spread through air spaces (STAS) describes a pattern of invasion seen in lung cancer, where cancer cells are observed spreading into the air spaces in the lung tissue outside of the tumour. The presence of STAS has been associated with a higher risk of recurrence and worse overall survival in patients with adenocarcinoma of the lungs, especially in those with early-stage disease. Recognizing STAS can therefore provide valuable prognostic information and help in risk stratification.

Pathologists identify STAS by carefully examining the lung tissue surrounding the tumour under a microscope. They look for tumour cells or clusters of cells within the air spaces that are separate from the main tumour and not attached to the tumour edge, often located at a distance from the tumour mass itself. These cells can be free-floating or attached to the alveolar walls but are distinguishable from the primary tumour and not explained by other processes such as artefact or lymphovascular invasion.

Multiple tumours

It is not uncommon for more than one tumour to be found in the same lung. 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.​

Pleural invasion

Pleural invasion refers to the spread of cancer cells into the pleura, which is the thin layer of tissue that surrounds the lungs and lines the inside of the chest cavity. There are two layers of the pleura: the visceral pleura, which sticks to the lungs, and the parietal pleura, which lines the chest wall and diaphragm. Pleural invasion by lung cancer means that the tumour has grown beyond the lung tissue itself and into the surrounding pleural layers.

Pleural invasion is important both for determining the pathologic stage and for prognosis:

• Tumour stage: The presence of pleural invasion is a significant factor in determining the stage of lung cancer. Tumours that invade the pleura are considered more advanced than those confined to the lung parenchyma (the functional tissue of the lung). According to the TNM classification system used for staging lung cancer, pleural invasion may increase the T category of the tumour, which signifies tumour size and extent. For example, a tumour that invades the visceral pleura might be classified as T2, while invasion into the parietal pleura or involvement of pleural effusion (fluid accumulation) could lead to a higher classification.
• Prognosis: Patients with lung cancer that has invaded the pleura generally have a poorer prognosis than those without pleural involvement. This is because pleural invasion reflects a more aggressive tumour that is more likely to spread and cause complications, such as pleural effusion, which can impair lung function and lead to symptoms like chest pain, cough, and shortness of breath.

Lymphovascular invasion​

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

Margins

​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.

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.

Lymph nodes

Lymph nodes are small immune organs found throughout the body. Cancer cells can spread through small lymphatic vessels from a tumour to lymph nodes. 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.

Pathologic stage (pTNM)

​The pathologic stage for adenocarcinoma of the lung is based on the TNM staging system, an internationally recognized system 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 a more advanced disease and a worse prognosis.

Tumour stage (pT)

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)

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 examined.
• 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 any lymph nodes on the side of the body opposite (contralateral) to the tumour. This stage includes stations 1 through 6.

Treatment effect​

Treatment effect is described in your report only if you received either chemotherapy or radiation therapy before surgery to remove the tumour. 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%.

Learn more pathology

Atlas of pathology