Mesothelioma - Lungs and pleura -

This article will help you read and understand your pathology report for mesothelioma.

by Katherina Baranova MD and Matt Cecchini MD FRCPC, reviewed on February 21, 2020

Quick facts:

  • Mesothelioma is a cancer of the cells that cover the outside of the lung and inner portion of the chest wall.
  • It is strongly linked to asbestos exposure and smoking.
  • There are three types of mesothelioma: epithelioid, biphasic and sarcomatoid.
  • Your pathology report will include important information such as histologic type and whether cancer cells have spread to other parts of the body.

The anatomy of the lungs and pleura

Your lungs are located within your chest in a space known as the pleural cavity or pleural space. The surface of your lungs and chest wall are covered by a thin type of tissue called the pleurae (singular pleura). The pleura that covers the lung is called the visceral pleura and the pleura that covers the chest wall is known as the parietal pleura. The two layers of pleurae can be understood as a balloon within a balloon. The inner (visceral) pleura and outer (parietal) pleura are separated by a thin space called the pleural cavity.

Lung pleura

Pathologists call the pleural cavity a potential space because it is not usually filled with air. In normal conditions there is a thin layer of fluid between the two layers of pleura. Under the microscope the pleura is made up of a layer of cells called mesothelial cells. These cells are small, flat to cuboidal cells, with well-defined cell borders . The part of the cell that holds the genetic material of the cell, the nucleus, is usually found in the center of the cell.

What is mesothelioma?

Mesothelioma is a type of cancer that starts from the mesothelial cells that line the pleura. Mesothelioma can start in any location where mesothelial cells are normally found, although the most common location is in the parietal pleura. Another name for mesothelioma is malignant 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 basket weave appearance.

How do pathologists make this diagnosis?

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 making a tumor, or spreading outside of the pleura into the surrounding tissue or the lungs. The movement of mesothelial cells into surrounding tissues is called invasion.

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 distinguish between mesothelioma and other conditions, some pathologists may use other immunohistochemistry tests including BAP1 and mTAP. Normal cells in your body will make these proteins. However, these proteins are not produced in many cases of mesothelioma. If these proteins are not detected in the immunohistochemistry test this may help your pathologist 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.

You may see the name of the procedure in your pathology report. The name of the procedure will depend on the amount of tissue removed.

Types of procedure include:

  • Extrapleural pneumonectomy – This procedure involves the removal of lung, pericardium (membrane covering the heart), part of the diaphragm and parietal pleura.
  • Extended pleurectomy/decortication – This procedure involves the removal of the visceral and parietal pleura along with resection of the pericardium (membrane covering the heart) and the hemidiaphragm.
  • Pleurectomy/decortication – This procedure involves the removal of the visceral and parietal pleura.
  • Partial pleurectomy – This procedure involves the removal of a portion of pleura tissue.

Histologic type

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.

Types of mesothelioma

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 tumor 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.

Number of tumours (tumor focality)

Most mesotheliomas grow as a single large tumour that covers both the parietal and visceral pleura. It is often difficult to determine where the tumour stops and the normal, healthy pleural begins. Some mesotheliomas, however, grow as a smaller tumour that is easy to separate from the surrounding normal, healthy pleura. Pathologists describe these tumours as localized mesothelioma.

Patients with localized mesothelioma have a better prognosis and may be able to undergo successful resection of the tumor.

Margins

If you underwent a complete resection with an extrapleural pneumonectomy, your pathologist will look for tumor in closest proximity to the resected edge of the specimen

Treatment effect​

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.

Lymph nodes

Lymph nodes are small immune organs located throughout the body. Cancer cells can travel from the tumour to a lymph node through lymphatic channels located in and around the tumour. The movement of cancer cells from the tumour to a lymph node is called a 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 cancer cells. Lymph nodes that contain cancer cells are called positive while those that do not contain any cancer cells are called negative.

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

Pathologic stage

​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 worse prognosis.

The pathologic stage will only be described in your report after the entire tumour has been removed. It will not be included after a biopsy.

Mesothelioma staging

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 tumor.

  • T1 –  Tumor only involves the pleura
  • T2 – Tumor has spread into the diaphragm or the lung
  • T3 – Potentially resectable tumor that involves additional structures such as the mediastinal fat or the chest wall
  • T4 – Advanced technically unresectable tumor involving structures such as rib(s), other organs, spine or heart.

Nodal stage (pN) for mesothelioma

Mesothelioma is given a nodal stage between 0 and 2 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 in the hilum or mediastinum from the same side as the tumor.
  • N2 -Cancer 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 cancer 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.

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