Adenosquamous carcinoma of the lung

by Jason Wasserman MD PhD FRCPC
June 17, 2025

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Adenosquamous carcinoma is a type of lung cancer that contains two distinct kinds of cancer cells: glandular cells and squamous cells. Glandular cells normally produce mucus and other substances that help keep the airways moist, while squamous cells typically line the inside surface of the airways. Due to this combination, adenosquamous carcinoma exhibits features of two other types of lung cancer: adenocarcinoma (derived from glandular cells) and squamous cell carcinoma (derived from squamous cells). This tumour is known for its aggressive behaviour and higher risk of spreading.

What are the symptoms of adenosquamous carcinoma of the lung?

Common symptoms include:

• A persistent cough that gets worse over time.

• Coughing up blood.

• Shortness of breath.

• Chest pain.

If the tumour has spread to other parts of the body, additional symptoms may appear depending on the location involved. For example, if the tumour spreads to bones, it may cause bone pain or weaken the bone, increasing the risk of fracture (called a pathologic fracture).

What causes adenosquamous carcinoma of the lung?

The exact causes of adenosquamous carcinoma of the lung are not fully understood, but several known risk factors increase the likelihood of developing this cancer:

• Smoking tobacco: This is the most common cause of all types of lung cancer.

• Radon exposure: A radioactive gas found in some homes.

• Asbestos exposure: Often linked to occupations such as construction, mining, or shipbuilding.

• Other harmful substances: Chemicals and industrial pollutants.

• Genetic factors: Family history and inherited conditions may also increase risk.

How is this diagnosis made?

The diagnosis of adenosquamous carcinoma typically begins with imaging tests, such as a chest X-ray or CT scan, followed by the removal of a small sample of lung tissue through a biopsy or fine needle aspiration (FNA). The tissue sample is examined under a microscope by a pathologist (a doctor specialized in diagnosing diseases by looking at tissue samples).

If the biopsy confirms the tumour is adenosquamous carcinoma, surgery may then be performed to remove the entire tumour. The type of surgery depends on the size and location of the tumour in the lung:

• Wedge resection: Removal of small tumours near the outer edge of the lung.

• Lobectomy: Removal of a lobe of the lung for larger tumours.

• Pneumonectomy: Removal of an entire lung for tumours close to the center or large tumours.

What does adenosquamous carcinoma look like under the microscope?

Under the microscope, adenosquamous carcinoma contains a mixture of two different cancer cell types:

• Glandular cells: Often arranged in glandular structures (similar to glands) or in solid groups. These cells sometimes line the alveoli (air sacs) in a pattern called lepidic.

• Squamous cells: Usually form large groups, and they can be described as:

  • Keratinizing: When cells produce a large amount of keratin (a protein that makes the cells appear pink under a microscope).

  • Non-keratinizing: When cells do not produce much keratin (making them appear more blue under a microscope).

What additional tests may be performed to confirm the diagnosis?

Your pathologist may use special tests called immunohistochemistry (IHC) to help confirm the diagnosis and distinguish adenosquamous carcinoma from other types of lung cancer. Immunohistochemistry helps identify specific proteins produced by cancer cells. For adenosquamous carcinoma, typical results include:

• TTF-1: Positive in glandular cells.

• p40 and CK5: Positive in squamous cells.

• Chromogranin and synaptophysin: Typically negative in both the glandular and squamous cells.

Spread through air spaces (STAS)

Spread through air spaces (STAS) describes a pattern of lung cancer growth where cancer cells spread into nearby air spaces within the lung. The presence of STAS often means a higher risk of the cancer returning (recurrence) and generally indicates a poorer prognosis, especially for early-stage tumours.

Pathologists examine the lung tissue surrounding the tumour under a microscope to determine if cancer cells are floating freely or attached separately to the alveolar walls, away from the main tumour mass.

Multiple tumours in the lung

It is possible to have more than one tumour in the lung. When multiple tumours are found, your pathology report will describe each tumour separately.

There are two reasons why multiple tumours might occur:

• Spread from one tumour: Likely if all tumours are the same type (such as all being adenosquamous carcinomas). Smaller tumours are called nodules if found on the same side of the lung, and metastases if found on the opposite lung.

• Separate tumours: If tumours are of different types (for example, one adenosquamous carcinoma and one squamous cell carcinoma), they are likely to have developed separately. These tumours are considered separate primary cancers.

Pleural invasion

The pleura is a thin lining surrounding the lungs and the inside of the chest wall. When cancer cells spread to the pleura, it is referred to as pleural invasion. Pleural invasion is important because it typically means:

• Higher tumour stage: Cancer that invades the pleura is considered more advanced.

• Poorer prognosis: Pleural invasion often leads to complications, such as fluid buildup (pleural effusion), which can cause shortness of breath, chest pain, and cough.

Lymphovascular invasion

Lymphovascular invasion means cancer cells have entered small vessels (blood vessels or lymphatic channels) within the lung tissue. This is important because cancer cells in these vessels can travel to lymph nodes or distant parts of the body, leading to further metastasis (spread).

Margins

In pathology, a margin refers to the edge of tissue removed during surgery to remove a tumour. After lung surgery, pathologists carefully examine all of these tissue edges under a microscope to determine if the tumour has been completely removed.

Margins assessed in lung cancer surgeries typically include:

• Bronchial margin – This is where the surgeon cuts through the airway.

• Vascular margin – These are the areas where large blood vessels near the tumour are cut.

• Parenchymal margin – This margin includes the edge of lung tissue around the tumour.

• Pleural margin – The pleura is a thin lining surrounding the lung, and this margin is examined to determine if the tumour grows close to or through this lining.

Margins can be described in two ways:

• Negative margin – No cancer cells are seen at any cut edge. This indicates that the tumour has likely been entirely removed, which is the goal of surgery.

• Positive margin – Cancer cells are seen at the cut edge of the tissue. A positive margin means there could still be tumour cells remaining in your body. Patients with a positive margin may require additional treatments, such as a second surgery or radiation therapy, to remove any remaining tumour cells and reduce the risk of recurrence.

The status of the margins helps your doctor determine the need for additional treatment and plays an important role in predicting the likelihood of the tumour growing back.

Lymph nodes

Lymph nodes are small, bean-shaped organs that play an essential role in the immune system. They are connected throughout the body by small channels called lymphatic vessels. Cancer cells can spread from a tumour through these lymphatic vessels and into nearby lymph nodes—a process called lymph node metastasis.

Lymph nodes in the lungs and chest are grouped into specific areas, known as lymph node stations. There are 14 different lymph node stations, each with a specific location:

• 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 (aortopulmonary window) lymph nodes.

• Station 6: Para-aortic lymph nodes (near the ascending aorta or phrenic nerve).

• Station 7: Subcarinal lymph nodes (below the carina, where the trachea splits into bronchi).

• Station 8: Paraesophageal lymph nodes (alongside the esophagus below the carina).

• Station 9: Pulmonary ligament lymph nodes.

• Station 10: Hilar lymph nodes (at the lung hilum, where airways enter the lung).

• Station 11: Interlobar lymph nodes (between lung lobes).

• Station 12: Lobar lymph nodes (within lung lobes).

• Station 13: Segmental lymph nodes (within lung segments).

• Station 14: Subsegmental lymph nodes (within smaller lung subsegments).

If lymph nodes are removed during surgery, a pathologist carefully examines them under a microscope to see if they contain cancer cells. The pathology report typically includes:

• The total number of lymph nodes examined.

• The locations (stations) of the lymph nodes examined.

• The number of lymph nodes containing cancer cells.

• The size of the largest group of cancer cells (often called a “focus” or “deposit”).

Lymph node examination provides important information that helps your doctor determine the cancer’s pathologic nodal stage (pN). It also helps predict the likelihood that cancer cells may have spread to other parts of the body, guiding decisions about additional treatments such as chemotherapy, radiation therapy, or immunotherapy.

Biomarkers for adenosquamous carcinoma of the lung

Biomarkers are specific molecules found inside tumour cells. These molecules help doctors understand how the tumour behaves and how it might respond to different treatments. Testing for biomarkers is important in lung cancer because some tumours contain genetic changes or alterations that make them respond well to targeted therapies. Targeted therapies are drugs designed specifically to attack cancer cells with these genetic changes. Identifying these biomarkers helps doctors choose the most effective treatment options.

Pathologists look for biomarkers using specialized laboratory tests.

Two common tests include:

• Next-generation sequencing (NGS) – This test examines many genes at the same time to find mutations (changes in the genetic material of tumour cells). NGS can quickly identify multiple biomarkers from a single tissue sample.

• Immunohistochemistry (IHC) – This test uses special stains that attach to specific proteins produced by cancer cells. When these proteins are present, the tumour cells change colour under the microscope. IHC helps confirm whether certain biomarkers are present in the tumour.

Common biomarkers tested in adenosquamous carcinoma of the lung

Your pathology report may include information about the following biomarkers. Each biomarker can help guide your treatment and provide important information about your tumour.

• EGFR: Mutations (changes) in the EGFR gene are common in lung cancer, particularly in individuals who have never smoked, women, and those of East Asian ancestry. Tumours with EGFR mutations often respond very well to targeted therapies called EGFR inhibitors. Your report will describe the tumour as EGFR-positive if a mutation is found. If no mutation is found, it will be called EGFR-negative.

• ALK: Changes in the ALK gene, known as ALK rearrangements or fusions, lead to tumour growth and are often found in younger patients or non-smokers. Tumours with ALK gene rearrangements usually respond well to medications called ALK inhibitors. Your report will say your tumour is ALK-positive if this change is present. If it is not present, your tumour will be ALK-negative.

• ROS1: ROS1 rearrangements (fusions) cause cancer cells to grow quickly. ROS1-positive tumours typically respond well to targeted ROS1 inhibitor therapies. If your tumour has a ROS1 rearrangement, it will be described as ROS1-positive. If no rearrangement is found, it will be described as ROS1-negative.

• BRAF: Certain mutations in the BRAF gene can cause tumour cells to grow rapidly. Tumours with specific BRAF mutations, particularly the V600E mutation, can be treated with BRAF inhibitors. If a BRAF mutation is found, your tumour will be described as BRAF-positive. If no mutation is found, it will be called BRAF-negative.

• MET: Mutations in the MET gene, especially mutations leading to “MET exon 14 skipping,” cause increased tumour growth. MET-positive tumours often respond to targeted therapies known as MET inhibitors. Your pathology report will describe your tumour as MET-positive if this mutation is present. If no mutation is found, your tumour will be MET-negative.

• RET: RET rearrangements or fusions result in uncontrolled tumour growth. Tumours with RET fusions usually respond very well to RET inhibitors. Your report will state that your tumour is RET-positive if a fusion is found. If a fusion is not found, it will be described as RET-negative.

• NTRK1-3: NTRK gene fusions are rare but can strongly promote tumour growth. Tumours with NTRK fusions usually respond to targeted medications known as TRK inhibitors. If an NTRK fusion is detected, your tumour will be described as NTRK-positive. If not, it will be described as NTRK-negative.

• KRAS: KRAS mutations are common in lung cancers, especially among smokers. Historically, KRAS-positive tumours were difficult to treat, but recent drugs targeting a specific KRAS mutation (KRAS G12C) have shown promising results. If a KRAS mutation is present, your tumour will be described as KRAS-positive. If no mutation is detected, your tumour is KRAS-negative.

• ERBB2 (HER2): ERBB2 mutations (also known as HER2 mutations) can drive tumour growth, particularly in non-smokers. Tumours with HER2 mutations may respond to targeted therapies currently under investigation or available in specialized centres. If your tumour has an ERBB2 mutation, it will be described as ERBB2-positive. If no mutation is found, it will be ERBB2-negative.

• NRAS: Mutations in the NRAS gene occur most commonly in tumours of people who have smoked. Currently, targeted therapies specific to NRAS mutations are limited; however, identifying this mutation can still aid in understanding tumour behaviour. Your tumour will be described as NRAS-positive if a mutation is found or NRAS-negative if no mutation is present.

• MAP2K1 (MEK1): MAP2K1 mutations are more common among smokers and are associated with increased tumour growth. Currently, treatments specifically targeting MAP2K1 mutations are still being studied. Your pathology report will indicate if a MAP2K1 mutation is present (MAP2K1-positive) or not (MAP2K1-negative).

• NRG1: NRG1 gene rearrangements are rare but significant because they can promote rapid tumour growth. Researchers are actively investigating targeted treatments for tumours with NRG1 rearrangements. Your tumour will be described as NRG1-positive if this rearrangement is found. If it is not found, it will be NRG1-negative.

Why are biomarker tests important for treatment?

Identifying these biomarkers in your tumour is essential because they help doctors choose the most effective treatments. Some biomarkers match specific drugs that directly target tumour cells. These treatments often work better and have fewer side effects than traditional chemotherapy.

If your tumour does not have biomarkers that match available targeted treatments, your doctor may recommend other options, such as chemotherapy or immunotherapy. Your medical team will help you understand your test results and the best treatment options available for you.

Pathologic staging (pTNM)

Pathologic staging describes how far the cancer has spread based on the TNM system. This system provides important information about prognosis and treatment decisions.

Tumour stage (pT)

The pathologic tumour stage describes the size and extent of the primary lung tumour. It ranges from 1 to 4 and helps determine the prognosis and the best treatment approach.

• T1: The tumour is no larger than 3 centimeters and is limited to the lung, without involving nearby structures.

• T2: The tumour is larger than 3 centimeters but no larger than 5 centimeters, or it invades the visceral pleura (the lung’s covering), or it partially blocks an airway (bronchus), but is not close to the lung hilum.

• T3: The tumour is larger than 5 centimeters but no larger than 7 centimeters, or it has directly invaded nearby structures such as the chest wall, pericardium (heart covering), diaphragm, or has separate tumour nodules within the same lung lobe.

• T4: The tumour is larger than 7 centimeters, or it has invaded vital structures such as the heart, major blood vessels, trachea, esophagus, spine, or has separate tumour nodules in a different lobe of the same lung.

Nodal stage (pN)

The pathologic nodal stage is based on the number of lymph nodes that contain cancer cells and the location of the lymph nodes involved.

• NX: No lymph nodes submitted.

• N0: No cancer cells in lymph nodes.

• N1: Cancer cells in lymph nodes close to the tumour (stations 10–14).

• N2: Cancer cells in lymph nodes in the middle of the chest (stations 7–9).

• N3: Cancer cells in lymph nodes far from the tumour or on the opposite side of the chest (stations 1–6).

Treatment effect

If you had chemotherapy or radiation therapy before surgery, the treatment effect describes how well the tumour responded. Pathologists measure the amount of viable (living) tumour tissue remaining after treatment, expressed as a percentage. A lower percentage of viable tumour indicates a better response to treatment.

Prognosis of adenosquamous carcinoma of the lung

Adenosquamous carcinoma often has a poorer prognosis compared to other lung cancers due to its aggressive nature and tendency to spread early. However, prognosis depends significantly on the stage at which the diagnosis is made. Early-stage tumours typically have a better outlook than advanced-stage tumours.

Questions to ask your doctor

If you have been diagnosed with adenosquamous carcinoma, consider asking:

• What is my tumour stage, and what does it mean?

• Were the surgical margins clear (negative)?

• Were lymph nodes involved?

• Will I need additional treatment like chemotherapy or radiation?

• Should I have genetic testing to guide treatment?

• How frequently should I be followed up for monitoring?

• Are there clinical trials available for my condition?