Mesothelioma

by Katherina Baranova MD and Matt Cecchini MD FRCPC
June 21, 2025

Mesothelioma is a type of cancer that starts from specialized cells called mesothelial cells. These cells form a thin lining around specific internal organs, such as the lungs, heart, and abdominal organs. This lining is called the mesothelium. Mesothelioma most commonly affects the lining around the lungs (called the pleura) but can also affect the lining around the heart (pericardium) or abdominal cavity (peritoneum). Another name for this type of cancer is malignant mesothelioma.

What causes mesothelioma?

The most common cause of mesothelioma is asbestos exposure. Asbestos is a mineral previously used in construction materials and insulation. When asbestos fibers are inhaled, they can become trapped in the lining of the lungs or abdomen, causing inflammation and damage over many years. This damage can eventually lead to the development of mesothelioma.

Some people with mesothelioma have a genetic risk due to inherited changes in specific genes, such as BAP1. People born with changes in this gene have a higher chance of developing mesothelioma even after minimal asbestos exposure.

Mesothelioma can occasionally develop in people who have no known history of asbestos exposure or genetic changes.

What are the symptoms of mesothelioma?

The symptoms of mesothelioma depend on the area of the body affected. For pleural mesothelioma (in the lining of the lungs), common symptoms include:

• Shortness of breath.

• Chest pain or discomfort.

• Persistent cough.

• Unexplained weight loss.

• Night sweats or fever.

• Swelling in the chest wall or neck.

Symptoms of pericardial mesothelioma (around the heart) often include:

• Chest pain.

• Difficulty breathing, especially when lying down.

• Fatigue.

• Irregular heartbeats or palpitations.

Symptoms can start mild and get worse over time. It is important to discuss these symptoms with your doctor, especially if you have a known history of asbestos exposure.

How is mesothelioma diagnosed?

The diagnosis of mesothelioma is typically made after a small tissue sample is removed during a procedure called a biopsy. This biopsy is often done by inserting a needle or small surgical instrument into the affected area.

Because mesothelioma can look similar to other conditions (such as lung infections or metastatic cancers), your pathologist may perform additional tests, including:

• Immunohistochemistry (IHC): This test helps identify proteins unique to mesothelioma cells.

• Fluorescence in situ hybridization (FISH): This test looks for specific genetic changes, such as the loss of a gene called CDKN2A, which is common in mesothelioma.

What do mesothelioma cells look like under the microscope?

When examining mesothelioma under a microscope, pathologists classify the tumour into three main types based on the appearance of the cells:

• Epithelioid mesothelioma: The most common type. The cells are rounded and tend to stick together, forming structures like glands or tubules.

• Sarcomatoid mesothelioma: Made up of long, spindle-shaped cells that tend to spread widely into surrounding tissues. This type often grows and spreads faster.

• Biphasic mesothelioma: A mixture of both epithelioid and sarcomatoid cells. Pathologists must see at least 10% of each type to diagnose this.

Another subtype is desmoplastic mesothelioma, which is related to the sarcomatoid type. It appears as dense scar-like tissue and can be challenging to diagnose.

The cell type matters because epithelioid mesothelioma usually has a better prognosis, while sarcomatoid and biphasic types tend to behave more aggressively.

What other tests help confirm the diagnosis?

Your pathologist will use tests such as immunohistochemistry (IHC) and fluorescence in situ hybridisztion (FISH) to confirm mesothelioma.

Immunohistochemistry (IHC)

IHC is used to identify specific proteins in the tumour cells. Mesothelioma cells typically show these results:

• Calretinin – Positive.

• WT-1 – Positive.

• D2-40 – Positive.

• Cytokeratin 5/6 – Positive.

• Claudin-4, MOC-31, BerEP4, TTF-1 – Usually negative (these are markers of other cancers).

Additional helpful markers include:

• BAP1: Normally, cells show positive nuclear staining for BAP1. Mesothelioma cells often lose BAP1 staining (negative result), helping distinguish mesothelioma from non-cancerous conditions.

• MTAP: Loss of MTAP protein staining is also common in mesothelioma and indicates loss of the CDKN2A gene.

Fluorescence in situ hybridization (FISH)

FISH testing helps identify whether genetic material has been lost or moved. The most important change tested is the loss of the CDKN2A gene. Loss of this gene is strongly associated with mesothelioma and typically indicates a more aggressive tumour.

Lymphovascular invasion

Cancer cells can spread into tiny blood vessels or lymphatic channels, a process called lymphovascular invasion. Blood vessels carry blood throughout the body, while lymphatic channels carry lymph fluid, which plays a crucial role in immune function. When tumour cells enter these channels, they can spread to other parts of the body, such as lymph nodes, the liver, or bones. Finding lymphovascular invasion means a higher risk of cancer spreading.

Margins

A margin is the healthy tissue surrounding a tumour that is removed during surgery. Pathologists examine margins carefully to ensure all cancer has been removed.

• A negative margin means no tumour cells are found at the cut edge of the tissue.

• A positive margin means tumour cells are present at the cut edge. This increases the risk that cancer will come back in the same place and may require additional treatment.

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.

Pathologic stage

Mesothelioma is staged using the TNM system, which considers:

Tumour size and spread (T-stage)

• T1: Tumour limited to the pleura on one side.
• T2: Tumour involving diaphragm or lung tissue.
• T3: Tumour involving deeper layers (such as chest wall).
• T4: Extensive tumour involving heart, spine, or other important organs.

Lymph node involvement (N-stage)

• N0: No tumour cells found in lymph nodes.
• N1: Tumour cells found in lymph nodes on the same side as the tumour.
• N2: Tumour cells found in lymph nodes farther away or on the opposite side.

Metastatic disease (M-stage)

• M0: No tumour cells in distant sites.
• M1: Tumour cells found in distant sites (e.g., liver or brain).

Higher numbers in each category indicate more advanced disease and usually a poorer prognosis.

Prognosis

The prognosis (expected outcome) for mesothelioma depends on several factors:

• Type of mesothelioma: Epithelioid has the best prognosis; sarcomatoid and biphasic types are more aggressive.

• Stage of the tumour: Early-stage tumours have a better prognosis than advanced ones.

• Lymph node involvement and metastasis: If tumour cells are in lymph nodes or distant organs, prognosis is generally poorer.

• Genetic factors: Loss of genes such as BAP1 or CDKN2A usually means a more aggressive tumour.

Mesothelioma is generally an aggressive cancer with a challenging prognosis. However, early detection, accurate diagnosis, and modern treatments can improve outcomes significantly.

Questions to ask your doctor:

• What type of mesothelioma do I have?

• What is the stage of my mesothelioma, and how does that affect my treatment options?

• Do my pathology results show any genetic changes such as BAP1 or CDKN2A loss?

• Should my family members undergo genetic testing?

• Will I need additional treatments after surgery, such as chemotherapy, immunotherapy, or radiation therapy?

• What is my prognosis given the specific features of my tumour?

• How often should I have follow-up visits and scans?

• Are there clinical trials available that I could join?

• What support resources are available for mesothelioma patients and families?