A. Definition of pleural mesothelioma
Pleural mesothelioma is a cancer that arises in the double layered covering that occurs around your lungs, called the pleura.1
The pleura has a cell type called mesothelial cells which is the origin of the cancer and hence the name mesothelioma.
One of the double layers of pleura is normally attached to the inside of the chest wall and the other is around the air spaces of the lung. There is a small space between these two layers called the pleural space. The pleura and pleural space help with the expansion of the lung synchronously with the movement of the chest wall.
This sort of covering occurs in other organs too, such as the heart and abdominal organs. In these instances they are called by their respective location. Eg. peri cardial mesothelioma in the heart or peritoneal mesothelioma in the abdomen.
B. Importance of understanding symptoms and treatments
If there is a growth or a collection in the pleural space, this obstructs the expansion of lungs.
In pleural mesothelioma there is an excessive and uncontrolled growth of mesothelial cells just like any other cancer.This growth occurs in pleura and pleural space, and interferes with the smooth expansion of the lungs. This is felt as adifficulty in breathing by the patient.
Even though Mesothelioma is a rare cancer, it is important that symptoms such as shortness of breath should be brought to the attention of a doctor quickly.
Pleural mesothelioma is caused mostly due to exposure to Asbestos dust. This is a cancer that’s unfortunately difficult to cure completely. The treatment options that are available, merely help to control the symptoms and reduce the growth. .
Symptoms of pleural mesothelioma
Overview of common symptoms
The symptoms of malignant pleural mesothelioma, (malignant meaning cancerous) can be broadly categorized into two groups.
- Shortness of breath
- Chest pain
- Persistent cough
These respiratory symptoms are all caused by the growth or thickening in the pleura and sometimes from fluid collection that accumulates in the pleural space, called a pleural effusion. The symptoms are caused due to the impairment of lung expansion and the irritant and pressure effects.
These general/ ‘non specific’ symptoms occur throughout the body due to substances produced by the cancer that are circulating around the body. They are common to many cancers.
- Unexplained weight loss
- Night sweats
Causes and risk factors
Exposure to Asbestos fibres is the most common cause for Mesothelioma and this has been strongly supported by research.2
Link to asbestos exposure
Exposure to Asbestos fibres are known to occur in many different occupations. Asbestos material ,when disrupted during their usage or construction, has fibres that can be airborne and can get inhaled and deposited in the lung. These are resistant to breakdown by the body and persist in the lung causing a reaction. With time they can cause changes to the cells that lead to cancer. Reportedly, it takes about 30 to 40 years from the time of first exposure to Asbestos to develop mesothelioma.
Occupational and environmental risk factors
There are many occupations that are known to be high risk for Asbestos exposure. Employees at risk include shipyard workers, construction site workers, demolition crews and automotive and railway industry workers etc. It is believed that even the family members of these workers may be exposed to Asbestos fibres as they are carried in the clothing of the workers into their households. Exposure through the environment can only occur if someone lives close to a demolition site or a construction site. Just because a house roof is constructed from Asbestos does not mean its inhabitants are exposed, unless it’s decaying or disrupted in some way.
Other potential causes
However a few other risk factors have been lately reported, such as a genetic mutation called Bap-1 that can run in families.2 Radiotherapy given to the chest for another cancer and some other rare chemicals are also suspected to cause malignant pleural mesothelioma.
Diagnosing pleural mesothelioma
Medical history and physical examination
One or more of the above mentioned symptoms occurring over a long time, should alert a person to seek medical advice. A thorough occupational history, family history and past medical history should be taken by a clinician to explore risk factors.Physical examination may reveal some reduction of lung expansion.
- Chest X-ray
- CT scan
- MRI scan
The investigations would usually begin with a chest x-ray which may show pleural thickening or a pleural effusion like a haziness in the lung shadow.
If mesothelioma is suspected, the patient needs to be urgently referred for further investigations. A physical examination and chest x ray is not enough to rule out mesothelioma.5
One of the best modalities to investigate is a CT-scan with contrast material. MRI is also an additional imaging modality that is sometimes used to see spread of the disease to nearby structures. In addition investigations like PET -CT scans may be required to assess spread.
To diagnose Malignant pleural mesothelioma, a biopsy or in other words, a tissue sample from a suspected area in the pleura is a requirement.3
There are mainly two ways to obtain a piece of tissue from the suspected area.
This is when a camera is introduced to the pleural space in the chest and tissue is taken directly from the pleural thickening site. This is done in an operation theatre under sedation and/or anaesthesia.
- Needle biopsy
The other is to obtain tissue via a thick needle going through the skin on the chest over the suspected area of the pleura and obtaining a sample. This is more suitable for patients who are not medically suitable to undergo a procedure under sedation or anaesthesia.
Additionally tissue sampling can be done through a procedure called endobronchial ultrasound or EBUS. In this procedure, a small tube with ultra sound scanning facility, is introduced to your airway passage. This can be used to locate suspicious areas around the lung or even lymph nodes where cancer could have spread to. Then a needle can be passed through the same tube and tissue samples can be obtained.
In addition to a biopsy like this, tumour cells that are there in a fluid collection within the pleura can also be sampled. This is only enough to suspect mesothelioma but it is usually not recommended for a definitive diagnosis. This obtaining of cells collected in a pleural space collection is called cytology testing.
The cells and tissue obtained thus are processed and studied under the microscope. Additional tests such as immunohistochemistry is often recommended for diagnosis.6
Pleural mesothelioma also has subtypes; epithelioid mesothelioma, sarcomatoid mesothelioma and biphasic mesothelioma.1 This categorisation is based on their microscopic appearance and can indicate the severity of their outcome.. For example, sarcomatoid mesothelioma has a worse outcome compared to the other two subtypes.
Staging of pleural mesothelioma
Explanation of staging system
Staging means assessing how much the cancer has spread, based on a standard system.
The main components of the staging in Mesothelioma is based on the size of the cancer, whether it has spread to lymph nodes and to distant organs. This is called the TNM staging.
Information from this is used for surgical staging or the number staging method. 1
Stage 1 is when cancer is only in one side of the pleura in your body, either only in the outer covering, (1A) or inner covering(1B)
Stage 2 is when cancer involves both inner and outer pleural layers on one side of the body and also extends into the diaphragm( muscle between your chest cavity and abdomen that helps you breath) or lung tissue
Stage 3 is when cancer has spread to chest wall and / or to outer covering of the heart (pericardium) but can potentially be removed by surgery, or it has spread to lymph nodes of the same side
Stage 4 is when it has spread to the other side of the body, through the diaphragm to abdominal cavity, through to the inner pericardium or to the lymph nodes on the other side of the chest etc.
Importance of staging for treatment planning
Staging is important as stage 4 is considered inoperable where cancer cannot be resected by operation. But there are other instances where even at an earlier stage the cancer cannot be resected out.
Treatment for malignant mesothelioma often requires a multi modal approach.7,8 Because of the location in the pleura, it is hard to cut out all cancer and some cancer cells can be left behind and regrow. Therefore other additional treatment like radiotherapy and chemotherapy is needed. There are also some newer treatment methods like immunotherapy and targeted therapy that are used with some success.
Surgery for most cancers are done with either the aim to completely cure the disease or with palliative intent, meaning to reduce the bulk of the cancer and reduce discomfort to patients.The same principle applies in mesothelioma. Surgery is rarely done for curative intent as it is hard to resect all of the cancer.
Even if done to cure completely in selected, suitable patients, the surgery is still quite complex and can cause complications. One such surgery is extra pleural pneumonectomy which includes removal of pleura and lung and possibly part of diaphragm or pleurectomy with decortication4 which removes pleura without the lung.
Surgery is often accompanied by other treatments like chemotherapy.
Chemotherapy is a systemic treatment given to the entire body, so that cancer cells left behind anywhere can be killed. Since it works in the entire body, there can be general side effects.
There are drugs like Carboplatin and Cisplatin which are used for Malignant pleural mesothelioma.
- Radiation therapy
Radiation is used over the operated area to kill remaining cancer cells that are left behind.
Emerging and experimental treatments
There are some additional treatment methods that are fairly new and still need large clinical trials to confirm their effect.
This is one treatment method where certain drugs enhance some immune cells and mechanisms in your body to kill the cancer cells.
- Targeted therapy
Targeted therapy is a modality when the treatment aims to modify some component needed for cancer growth. This in turn interferes with the cancer growth and reduces the cancer progression. For example, there’s a substance in the body called VEGF which is useful for new blood vessel formation that is needed for cancer growth. Targeted therapy attempts to block VEGF from working. So, it blocks the process needed for cancer growth.
- Gene therapy
These are treatments that are still being investigated for their effectiveness.
C. Palliative care and symptom management
Palliative care is treatment aimed at making the patient comfortable by reducing the cancer bulk.
Surgically, some procedures like pleurodesis, prevents the cancer from collecting repeatedly in the pleural space by fusing the pleural layers together. Removing pleural fluid as it occurs as well as pain relief are some other methods.
Malignant pleural mesothelioma is a rare cancer occuring in the coverings of the lung and is chiefly due to asbestos exposure.
Pleural mesothelioma is hard to cure completely and treatment is often aimed at reducing the cancer bulk and reducing symptoms.
Main symptoms are breathlessness, chest pain, weight loss etc.
A chest x-ray is often not enough to detect mesothelioma. Patients need imaging such as CT scans and a biopsy. Cells collected in the pleural space can also be tested.
Cancer is then categorised into a stage to decide on the treatment approach.
Treatment is often multi-modal with surgery done to remove the bulk of cancer. Complete resection of cancer is usually not possible and additional treatment like radiotherapy or chemotherapy is needed.
Some newer treatments like immunotherapy and targeted therapy are also being trialed now.
- Pleural Mesothelioma: Asbestos Exposure, Symptoms, Prognosis [Internet]. Cleveland Clinic. Available from: https://my.clevelandclinic.org/health/diseases/15044-pleural-mesothelioma
- Malignant Mesothelioma | Malignant Mesothelioma Information [Internet]. www.cancer.org. [cited 2023 Jul 4]. Available from: https://www.cancer.org/cancer/types/malignant-mesothelioma.html
- Mayo Clinic. Mesothelioma - Symptoms and causes [Internet]. Mayo Clinic. 2019. Available from: https://www.mayoclinic.org/diseases-conditions/mesothelioma/symptoms-causes/syc-20375022
- Scherpereel A, Astoul P, Baas P, Berghmans T, Clayson H, de Vuyst P, et al. Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma. European Respiratory Journal. 2009 Aug 28;35(3):479–95.
- Diffuse malignant mesothelioma [Internet]. www.pathologyoutlines.com. Available from: https://www.pathologyoutlines.com/topic/pleuramesothelioma.html
- NHS Choices. Mesothelioma [Internet]. NHS. 2019. Available from: https://www.nhs.uk/conditions/mesothelioma/