by Katherina Baranova MD and Matt Cecchini MD FRCPC
May 26, 2022

What is mesothelioma?

Mesothelioma is a type of cancer that starts from specialized mesothelial cells. These cells are normally found on the outside surface of the lungs and the intra-abdominal organs such as the colon and small intestine. Another name for mesothelioma is malignant mesothelioma.

What causes mesothelioma?

Mesothelioma is associated with asbestos exposure in most, but not all cases. Many patients exposed to asbestos will also have areas where their pleura has become abnormally thick. These areas are called pleural plaques and they can usually be seen on imaging of the lungs (x-ray or CT scan). When examined under the microscope, pleural plaques are made up of dense collagen layers that can have a basketweave appearance.

How do pathologists make the diagnosis of mesothelioma?

The diagnosis of mesothelioma is usually made after a small sample of tissue is removed in a procedure called a biopsy. In some cases, additional surgery may be performed. The diagnosis of mesothelioma can be challenging because non-cancerous conditions such as infection or pleural effusions can lead to changes in the mesothelial cells that can look similar to cancer under the microscope. In order to diagnose mesothelioma, your pathologist needs to see mesothelial cells forming a tumor, or spreading outside of the pleura into the surrounding tissue or the lungs. The spread of mesothelial cells into surrounding tissues is called invasion.

What other tests may be performed to confirm the diagnosis?

When examined under the microscope, other types of cancer can look very similar to mesothelioma. Most pathologists will perform a test called immunohistochemistry to help them decide if the abnormal cells are mesothelial cells or cells from another part of the body.

When immunohistochemistry is performed, mesothelial cells will typically show the following results:

• WT-1 – Positive
• Calretinin – Positive
• D2-40 – Positive
• Cytokeratin 5/6 – Positive
• MOC-31 – Negative
• BerEP4 – Negative
• Polyclonal CEA – Negative
• TTF-1 – Negative

Pathologists usually require a combination of immunohistochemical tests to help them decide if the abnormal cells are mesothelial cells or if they are from another part of the body.

In order to distinguish between mesothelioma and other conditions, some pathologists may use other immunohistochemical tests including BAP1 and mTAP. Both of these proteins are normally found in tissues throughout the body. However, they are not typically seen in mesothelioma. For that reason, a negative result for BAP1 or mTAP supports the diagnosis of mesothelioma.

What are the types of mesothelioma?

There are three types of mesothelioma based on how the cells look when examined under the microscope. Pathologists decide the type by looking at the size and shape of the cells and the way the cells stick together.

• Epithelioid mesothelioma – This type is made up of small cells with oval to cuboidal shapes that connect together, often forming small tubular or papillary structures.
• Sarcomatoid mesothelioma – This type is made up of cells that are longer than they are wide. Pathologists describe these cells as spindle cells. Unlike the cells in the epithelioid type mesothelioma, the spindle cells do not stick together as well to form structures and they spread widely into the surrounding tissue.
• Biphasic mesothelioma – This type is made up of a mixture of epithelioid and sarcomatoid-type cells. To be called biphasic, your pathologist needs to see at least 10% of each cell type in the tissue samples examined under the microscope.

Desmoplastic mesothelioma is another type of mesothelioma that is related to the sarcomatoid type. Desmoplastic mesothelioma can be challenging for the pathologist to diagnose. The tumour is made up of dense fibrous tissue with abnormal spindle cells.

The histologic type is important because patients with the epithelioid type will typically have the best prognosis followed by biphasic then sarcomatoid. The histologic subtype may influence what surgical procedures or therapies are used to treat your specific type of mesothelioma.

What is a margin?

A margin is the normal tissue that surrounds a tumour and is removed with the tumour at the time of surgery. If you underwent a complete resection with an extrapleural pneumonectomy, your pathologist will look for tumor cells at the cut edge of the tissue.

If no tumour cells are seen at the cut edge of the tissue the margin is called negative. If tumour cells are seen at the very edge of the cut tissue, the margin is called positive. A positive margin is important because it is associated with a greater risk that the tumour will come back in the same location (local recurrence) after treatment.

What does treatment effect​ mean?

Some patients will receive chemotherapy or radiation therapy prior to the tumour being removed surgically. If you received either chemotherapy or radiation therapy prior to surgery your pathologist will examine the tumour under the microscope to see how much of the tumour is still alive (viable). This is called the treatment effect.

To determine the treatment effect, your pathologist will measure the amount of living (viable) tumour and divide that number by the amount of the total tumour. The treatment effect is usually described as greater or less than 50% of residual viable tumor.

The amount that your tumor responded to therapy may help your oncologist understand how well the tumor is treated by chemotherapy and may be used to help guide further treatment.

What are lymph nodes?

Lymph nodes are small immune organs located throughout the body. Tumour cells can travel from the tumour to a lymph node through lymphatic channels located in and around the tumour. The movement of tumour cells from the tumour to a lymph node is called lymph node metastasis.

Lymph nodes from the neck, chest, and lungs may be removed at the same time as the tumour. Your pathology report will describe the number of lymph nodes examined. Your pathologist will carefully examine each lymph node for tumour cells. Lymph nodes that contain tumour cells are called positive while those that do not contain any tumour cells are called negative.

Finding tumour cells in a lymph node increases the nodal stage (see Pathologic stage below) and is associated with a worse prognosis. The nodal stage will depend on where the lymph node with tumour cells was located.

How do pathologists determine the pathologic stage for mesothelioma?

​The pathologic stage for mesothelioma 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 mesothelioma

Mesothelioma is given a tumour stage between 1 and 4 based on invasion by the tumor into other structures and the resectability of the tumour (the ability to surgically remove).

Nodal stage (pN) for mesothelioma

Mesothelioma is given a nodal stage between 0 and 2 based on the presence or absence of tumour cells in a lymph node and the location of the lymph nodes that contain tumour  cells.

• NX – No lymph nodes were sent for pathologic examination.
• N0 – No tumour cells were found in any of the lymph nodes examined
• N1 – Tumour cells were found in at least one lymph node in the hilum or mediastinum from the same side as the tumor.
• N2 -Tumour cells were found in at least one lymph node from the opposite side of the mediastinum or outside of the chest.

​Metastatic stage (pM) for mesothelioma

Mesothelioma is given a metastatic stage of 0 or 1 based on the presence of tumour at a distant body site (for example, the brain). The metastatic stage can only be determined if tissue from a distant site is sent for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as pMX.