by Jason Wasserman MD PhD FRCPC
March 4, 2024

Adenosquamous carcinoma of the lung is a rare and aggressive form of non-small cell lung cancer (NSCLC) that exhibits characteristics of both adenocarcinoma and squamous cell carcinoma.

What are the symptoms of adenosquamous carcinoma of the lung?

Symptoms of adenosquamous carcinoma 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 causes adenosquamous carcinoma of the lung?

The exact causes of adenosquamous carcinoma remain largely unknown, but risk factors are consistent with those of other lung cancers: smoking, exposure to radon gas, asbestos, and other carcinogens. Genetic predispositions may also play a role in the development of this cancer type.

What is the prognosis for a person diagnosed with adenosquamous carcinoma of the lung?

The prognosis for individuals diagnosed with adenosquamous carcinoma of the lung generally tends to be poorer compared to other forms of NSCLC, primarily due to its aggressive nature and potential for early metastasis. Prognosis significantly depends on the stage at diagnosis, with early-stage cancers having a more favourable outcome compared to those diagnosed at an advanced stage.

How is this diagnosis made?

The initial diagnosis of adenosquamous carcinoma of 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.

Your pathology report for adenosquamous carcinoma of the lung

The information found in your pathology report for adenosquamous carcinoma of the lung depends on the type of procedure performed. Your pathology report after a small procedure such as a fine needle aspiration biopsy (FNAB) may provide only the diagnosis and the results of tests used to confirm the diagnosis such as immunohistochemistry (IHC). After a larger surgical procedure to remove the tumour, your pathology report may include additional information such as the tumour size, spread through air spaces (STAS), pleural invasion, and margins. If any lymph nodes were removed, they will be described as well. Molecular tests may be performed to look for genetic changes in the tumour and those results may be included in the biopsy report or after the tumour is removed. All of these topics are discussed in greater detail in the sections below.

Microscopic features of this tumour

Under the microscope, adenosquamous carcinoma presents a mix of two distinct types of cancer cells: glandular cells typical of adenocarcinoma and large squamous cells characteristic of squamous cell carcinoma. The glandular cells may be arranged in glands, solid nests, or in a lepidic pattern along preexisting alveolar structures. The squamous cells are typically arranged in large groups and the cells may be described as keratinizing if the cells are producing a large amount of a protein called keratin (that makes the cells look pink) or non-keratinizing if the cells are not producing a lot of keratin (which makes them look more blue).

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, adenosquamous carcinoma of the lung usually shows the following results:

• TTF-1 – Positive in the glandular part of the tumour.
• p40 – Positive in the squamous cell part of the tumour.
• CK5 – Positive in the squamous cell part of the tumour.
• Chromogranin – Negative.
• Synaptophysin – Negative.

Genetic changes found in adenosquamous carcinoma of the lung

Genetic changes commonly found in adenosquamous carcinoma 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 adenosquamous carcinoma 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 adenosquamous carcinomas. 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 adenosquamous carcinoma 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 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.

Pathologic stage (pTNM)

​The pathologic stage for adenosquamous carcinoma 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)

Adenosquamous carcinoma 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)

Adenosquamous carcinoma 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 will be 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

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