What are the other Names for this Condition? (Also known as/Synonyms)

• Malignant Pleural Mesothelioma
• Pleural Mesothelioma
• Primary Pleural Mesothelioma

What is Malignant Mesothelioma of Pleura? (Definition/Background Information)

• Malignant Mesothelioma of Pleura is a very uncommon, malignant tumor of the pleura, which is the outer membranous layer of the lungs. It is a primary lung tumor, indicating that the tumor is not found outside the pleura/lung
• A malignant mesothelioma is a malignancy of the mesothelial cells (membrane lining the various body cavities). Based on location of the tumor, 5 body sites have been identified which include:
  • Pleura (lung)
  • Peritoneum (abdomen)
  • Pericardium (heart)
  • Outer lining of the testis, called tunica vaginalis
  • Ovary
• Malignant Mesothelioma of Pleura may be associated with asbestos exposure (inhalation of asbestos dust or fibers), certain surgical procedures, and radiation treatment to cancers in the chest region. The cause of formation of the tumor is not well-established
• Large-sized tumors may cause chest pain, abnormal fluid collection in the pleura, breathing difficulties, and dizziness. The complications of Malignant Pleural Mesothelioma include obstruction of the airways, metastasis to various regions, and recurrence following its surgical removal
• The treatment of Malignant Mesothelioma of Pleura is undertaken through surgery. However, since it is difficult to remove the entire tumor, chemotherapy and/or radiation therapy may be proposed
• The prognosis of Malignant Mesothelioma of Pleura is generally poor due to impairment of lung function, local invasion, and metastasis of the malignancy to various body sites

Who gets Malignant Mesothelioma of Pleura? (Age and Sex Distribution)

• Almost 75% of all malignant mesotheliomas found in the body are Malignant Mesotheliomas of Pleura; hence, the lungs are the most common location for this tumor type
• Even though the tumor may occur in children and young adults, 4 out of 5 tumors (80% of the cases) are found in older adults above the age of 75 years
• Both males and females are affected, although males are at a higher risk by virtue of their occupation
• No racial or ethnic group preference is generally noted

What are the Risk Factors for Malignant Mesothelioma of Pleura? (Predisposing Factors)

Currently, no definitive risk factors are noted for the development of Malignant Mesothelioma of Pleura. But it may be associated with the following factors:

• Association with asbestos/fiberglass exposure is strongly noted; the tumors may often develop many years after exposure to these substances. Workers exposed to asbestos include the following and those involved in occupations such as:
  • Manufacturing of industrial products containing asbestos such as paints, insulation, floor tiles, ceiling, etc.
  • Construction workers, home builders
  • Electricians
  • Firefighters
  • Demolition workers
  • Military personnel
  • Those working in chemical plant manufacturing facilities, refineries, power plants, etc.
  • Shipyard workers
• Secondary asbestos exposure (inhalation) during the job, when one may be exposed being in the vicinity. The environmental asbestos exposure can occur in a variety of ways
• Iatrogenic tumors: Some tumors have been reported to form following medical treatment for angina pectoris
• Chronic smoking
• In rare cases, treatment for breast cancer or lymphoma of mediastinum using radiation therapy is also known to cause the formation of malignant mesothelioma
• Exposure to eronite, a type of naturally-occurring mineral fiber, in some parts of the world (e.g. Turkey)
• Family history of mesothelioma: Mutations in BAP1 gene that can run in some families can increase the risk for malignant mesothelioma. The gene mutation can also cause an increased risk for a variety of cancers, such as ocular melanoma, clear cell renal cell carcinoma, liver cancer including intrahepatic cholangiocarcinoma, melanoma of skin, etc. in such individuals
• In experimental animal models, simian virus 40 (SV40, which is generally found in monkeys and humans) has been shown to cause malignant mesothelioma. However, whether SV40 causes mesothelioma in humans is not yet definitely established

Note:

• The adverse health effect caused by smoking and exposure to asbestos may act as a combination factor in some individuals and result in a much amplified risk for mesothelioma
• In some cases, no association to any of the above factors may be identified

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Malignant Mesothelioma of Pleura? (Etiology)

The exact cause and mechanism of formation of Malignant Mesothelioma of Pleura is unknown. However, the tumor formation seems to be influenced by exposure to certain carcinogenic substances (such as asbestos fibers), radiation therapy for cancer, and medical procedures involving the heart.

• Mesotheliomas have been shown to have a variety of different genetic mutations
• Long-term exposure to asbestos:
  • Asbestos is a silicate mineral with a fibrous structure. Due to its high heat resistance, it is used as a versatile insulating material in several industries including construction, firefighting, automobile industry, etc. However, it is harmful to humans and is recognized as a hazardous material
  • It is researched that when the asbestos particles get into the body (part/site), they irritate the body tissue causing genetic damage. The entry into the human body may be through inhalation of asbestos dust particles or by inadvertently swallowing small-sized asbestos fibers
  • Generally it takes years to develop mesothelioma; around 10-50 years following exposure to asbestos or asbestos products
• In general, it is known that cancers form when normal, healthy cells begin transforming into abnormal cells - these cancer cells grow and divide uncontrollably (and lose their ability to die), resulting in the formation of a mass or a tumor
• The transformation of normally healthy cells into cancerous cells may be the result of genetic mutations. Mutations allow the cancer cells to grow and multiply uncontrollably to form new cancer cells
• These tumors can invade nearby tissues and adjoining body organs, and even metastasize and spread to other regions of the body

What are the Signs and Symptoms of Malignant Mesothelioma of Pleura?

The signs and symptoms of Malignant Mesothelioma of Pleura may include:

• The presence of large-sized tumors that are nodular in appearance, in the pleural cavity
• The tumor can spread and obstruct major blood vessels
• Tiredness or fatigue, shortness of breath or rapid breathing
• Chest pain or discomfort, such as feelings of heaviness/fullness of the chest
• Intermittent cough
• With respect to lung mesothelioma, right side lung involvement is more common than the left side (in a 3:2 ratio, per some study reports). In majority of cases, only one side is involved; the involvement of both sides simultaneously is very uncommon
• Low-grade fever and profuse sweating
• Fainting or feeling faint, dizziness
• Pleural effusion; an abnormal collection of fluid within the pleura (or lining of the lung)
• Swelling in the lower legs
• Weight loss

There are no signs and symptoms during the initial stages of tumor growth and development. Also, small-sized tumors usually do not cause any symptoms. But, occasionally they may become painful, if the surrounding structures are compressed.

How is Malignant Mesothelioma of Pleura Diagnosed?

The following tools may be used towards establishing a diagnosis of Malignant Mesothelioma of Pleura:

• Complete evaluation of family (medical) history, along with a thorough physical examination; including examination of the lungs
• X-ray of the chest
• CT or CAT scan with contrast of the chest may show the presence of a mass. This radiological procedure creates detailed 3-dimensional images of structures inside the body
• MRI scans of the lungs: Magnetic resonance imaging (MRI) uses a magnetic field to create high-quality pictures of certain parts of the body, such as tissues, muscles, nerves, and bones. These high-quality pictures may reveal the presence of the tumor
• Whole-body PET scan, bone scan of affected region to check for tumor metastasis. This helps with the staging of the tumor

Although the above modalities can be used to make an initial diagnosis, a tissue biopsy of the tumor is necessary to make a definitive diagnosis to begin treatment. The tissue for diagnosis can be procured in multiple different ways which include:

• Fine needle aspiration (FNA) biopsy of the tumor: A FNA biopsy may not be helpful, because one may not be able to visualize the different morphological areas of the tumor. Hence, a FNA biopsy as a diagnostic tool has certain limitations, and an open surgical biopsy is preferred
• Core biopsy of the tumor
• Open biopsy of the tumor
• Bronchoscopy: A special medical instrument, called a bronchoscope, is inserted through the nose and into the lungs to collect small tissue samples
• Thoracentesis: During thoracentesis, physicians use a special medical device called a cannula, to remove fluid between the lungs and the chest wall for examination
• Thoracoscopy: A medical instrument called a thoracoscope is inserted into the chest through tiny incisions, in order to examine and remove tissue from the chest wall, which is then analyzed further
• Thoracotomy: Thoracotomy is a surgical invasive procedure with special medical instruments to open-up the chest and remove tissue from the chest wall or the surrounding lymph nodes of the lungs
• Mediastinoscopy: A medical instrument called a mediastinoscope is inserted into the chest wall to examine and remove samples

Tissue biopsy of the tumor:

• A biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
• Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
• Sometimes, the pathologist may perform additional studies, which may include immunohistochemical stains, electron microscopy, and molecular studies to assist in the diagnosis

Note: Due to the rarity of these tumors, the diagnosis of this malignancy can be missed. It can even cause diagnostic challenges during a frozen section biopsy.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Malignant Mesothelioma of Pleura?

Complications due to Malignant Mesothelioma of Pleura could include:

• Large tumors can obstruct the bronchus (airways) and other adjoining organs/structures
• Severely impaired lung function
• Metastasis of the tumor to other sites in the body such as to the lymph nodes
• Recurrence of the tumor after surgery, when the entire tumor is not removed
• Blood loss during invasive treatment methods may be heavy
• Damage of vital nerves, blood vessels, and surrounding structures during surgery
• Side effects from chemotherapy (toxicity), radiation therapy (radiation fibrosis)

How is Malignant Mesothelioma of Pleura Treated?

Once a diagnosis of Malignant Pleural Mesothelioma has been made, the extent to which the tumor has spread is assessed, known as staging. The staging for Pleural Mesothelioma is based upon the AJCC (American Joint Committee on Cancer) TNM staging system.

The TNM system is based on the following 3 parameters:

• T: It indicates the extent of spread of the main (primary) tumor
• N: It is the spread of cancer to nearby (regional) lymph nodes; the cancer spreads to the lymph nodes initially
• M: It indicates whether the cancer has spread (metastasized) to other organs of the body. (The most common sites are the pleura on the other side of the body, the lungs, and the peritoneum.)

T groups: Higher numbers indicate more advanced cancers.

• TX: The main tumor cannot be assessed for some reason
• T0: There is no evidence of a main tumor (the cancer is found elsewhere instead)
• T1: Mesothelioma is in the pleura lining the chest wall on one side of the chest. It may or may not also affect the pleura lining the diaphragm (the thin breathing muscle below the lungs) or the mediastinum (the space between the lungs). It may also have spread to the pleura covering the lung
• T2: Mesothelioma is in the pleura lining the chest wall on one side of the chest. It is also in the pleura coating the diaphragm, the mediastinum, and the lung. It also has grown into at least one of the following:
  • The diaphragm
  • The lung itself
• T3: The mesothelioma has grown further but may still possibly be removed with surgery. The tumor is in the pleura lining the chest wall on one side of the chest, as well as the pleura coating the lung, the diaphragm, and the mediastinum. It also has grown into at least one of the following:
  • The first layer of the chest wall (called the endothoracic fascia)
  • The fatty tissue in the mediastinum
  • A single place in the deeper layers of the chest wall
  • The surface of the pericardium (outer covering layer of the heart)
• T4: The mesothelioma has grown too far to be removed completely with surgery. The tumor has grown into the pleura lining the chest wall on one side of the chest, as well as the pleura coating the lung, diaphragm, and mediastinum on the same side. It also has grown into at least one of the following:
  • More than one place in the deeper layers of the chest wall, including the muscle or ribs
  • Through the diaphragm and into the peritoneum
  • Any organ in the mediastinum (esophagus, trachea, thymus, blood vessels)
  • The spine
  • Across to the pleura on the other side of the chest
  • Through the heart lining (pericardium) or into the heart itself

N groups: Higher numbers indicate more advanced cancers.

• NX: The nearby lymph nodes cannot be assessed
• N0: No spread to nearby lymph nodes
• N1: Spread to lymph nodes within the lung and/or around the area where the bronchus enters the lung (called hilar or bronchial lymph nodes) on the same side as the main tumor
• N2: Spread to other lymph nodes on the same side as the main tumor, such as the subcarinal (around the point where the windpipe branches into the left and right bronchi) and the mediastinal lymph nodes. Also includes spread to the lymph nodes in the space just behind the breastbone (called internal mammary lymph nodes) and those near the diaphragm (called peridiaphragmatic)
• N3: Spread to lymph nodes near the collarbone on either side (supraclavicular lymph nodes), and/or spread to hilar or mediastinal lymph nodes on the side opposite the main tumor

M groups: Higher numbers indicate more advanced cancers.

• M0: No spread to distant organs or areas
• M1: The cancer has spread to distant sites. This can be to distant lymph nodes or to other organs

Stage grouping for Pleural Mesothelioma:

Once the T, N, and M categories have been assigned, this information is combined in a process called stage grouping to assign an overall stage of I, II, III, or IV. Patients with lower stage numbers tend to have a better prognosis.

Stage I: T1, N0, M0

• Mesothelioma has grown into the pleura lining the chest wall on one side of the chest
• It might or might not also affect the pleura lining the diaphragm (the breathing muscle) or the mediastinum (the space between the lungs)
• It may also have spread to the pleura covering the lung (T1). It has not spread to the lymph nodes (N0) or to distant sites (M0)

Stage II: T2, N0, M0

• Mesothelioma has grown into the pleura lining the chest wall on one side of the chest
• It also is in the pleura coating the diaphragm, the mediastinum, and the lung
• The cancer has also grown into the diaphragm or the lung itself (T2)
• It has not spread to the lymph nodes (N0) or to distant sites (M0)

Stage III: Either of the following

T1 or T2, N1 or N2, M0:

• Mesothelioma has grown into the pleura lining the chest on one side, and might or might not have grown into the pleura lining the lung, the diaphragm, or the mediastinum
• It might also have grown into the muscle of the diaphragm or the lung itself (T1 or T2)
• It has spread to lymph nodes in the chest on the same side as the main tumor (N1 or N2)
• It has not spread to distant sites (M0)

OR

T3, N0 to N2, M0:

• Mesothelioma is in the pleura lining the chest on one side, and has grown into the first layer of the chest wall, the fatty tissue in the mediastinum, a single place in the deeper layers of the chest wall, or the outer covering layer of the heart (T3)
• It might or might not have spread to lymph nodes in the chest on the same side as the tumor, but it has not spread to lymph nodes near the collarbone or on the opposite side of the chest (N0, N1, or N2)
• It has not spread to distant sites (M0)

Stage IV: Any of the following:

T4, any N, M0:

• Mesothelioma has grown into the pleura lining the chest on one side and has grown into more than one place in the deeper layers of the chest wall (including the muscle or ribs), through the diaphragm and into the peritoneum, into any organ in the mediastinum, into the spine, across to the pleura on the other side of the chest, and/or through the heart lining or into the heart itself (T4)
• It might or might not have spread to lymph nodes (any N). It has not spread to distant sites (M0)

OR

Any T, N3, M0:

• The tumor may or may not have grown into nearby tissues (any T)
• It has spread to lymph nodes near the collarbone on either side and/or to hilar or mediastinal lymph nodes on the side opposite the main tumor (N3)
• It has not spread to distant sites (M0)

OR

Any T, any N, M1:

• The mesothelioma might or might not have grown into nearby tissues (any T)
• It might or might not have spread to the lymph nodes (any N)
• It has spread to distant sites (M1)

(Source: “The AJCC system for staging Pleural Mesothelioma”; information provided by the American Cancer Society, February 2016)

Note: Currently, staging information is available only for Malignant Pleural Mesothelioma, since it is the most common mesothelioma subtype.

In general, Malignant Pleural Mesothelioma is a highly-aggressive cancer and the treatment can be challenging. A multidisciplinary approach with a team of healthcare specialists and experts from various medical fields may be necessary to treat the cancer at a healthcare institution that has the experience and expertise in dealing with such high-grade cancers.

The treatment measures for Malignant Mesothelioma of Pleura may include a combination of the following:

• Surgery: Complete excision where possible is attempted; though, it is difficult for the lung tumor to be removed completely. Even though it may not be curative, it can aid in the diagnosis and relieve obstructive symptoms. The surgical options may include:
  • Wedge resection: Wedge resection is a partial removal of the wedge-shape portion of the lung that contains the tumor cells (along with any surrounding healthy tissue)
  • Segmentectomy: Segmentectomy is also the partial removal of the lung with the tumor and any surrounding healthy tissue
  • Pulmonary lobectomy: It is a type of surgical procedure to partially remove a portion of a lung
  • Sleeve lobectomy: It is another surgical procedure to partially remove a portion of the lung and a part of the airway (bronchus)
  • Pneumonectomy: It is the surgical removal of the entire lung
• Radiation therapy and/or chemotherapy
• Total lung transplantation may be undertaken in some cases; when no distant metastasis has occurred and the primary tumor, which cannot be surgically removed, is confined to the lung
• Immunotherapy: It is a newer method of treatment that has shown promising results in some individuals. The healthcare provider will determine if immunotherapy is to be employed in treating the tumor
• Embolization (clotting the vessels in the tumor) may be used to provide temporary relief from the symptoms and reduce blood loss during a surgical procedure
• Follow-up care with regular screening and check-ups are important

How can Malignant Mesothelioma of Pleura be Prevented?

Current medical research has not established a way of preventing the formation of Malignant Mesothelioma of Pleura. However, the following factors may be considered to reduce the risk of cancer development:

• Avoid or stop smoking: Individuals, who are smokers or have a prior history of the condition or suffer from other lung diseases, should regularly follow-up with their primary care physician to ensure that their lung functions are normal
• Reducing exposure to known causative agents such as asbestos and asbestos products 
• Early detection of exposure to asbestos dust particles can help avoid further exposure
• Wearing appropriate respirators and masks while performing jobs that involve dust, chemicals, and metals
• While working in industry, maintain a clean work area that is dust-free. Also, regularly shower and change clothes after industrial work
• Ensure that industrial safety regulations for exposure to hazardous materials is adhered to at workplaces
• Ensure that the industries strictly comply with implementation of prevalent statutory codes on occupational safety measures, especially with respect to workplace exposure
• Undertake routine screening of individuals working in environment where exposure to asbestos is evident
• Government regulations have decreased or even eliminated the use of asbestos through increased safety measures and through the usage of substitute products (instead of asbestos)
• It is recommended that regular screening be undertaken for mesothelioma, if any of the following tumors are observed:
  • Clear cell renal cell carcinoma
  • Intrahepatic cholangiocarcinoma (a type of liver cancer)
  • Cutaneous melanoma
  • Uveal or ocular melanoma

Due to its high metastasizing potential and recurrence rate, regular medical screening at periodic intervals with blood tests, scans, and physical examinations, are mandatory for those who have already been treated for this tumor.

What is the Prognosis of Malignant Mesothelioma of Pleura? (Outcomes/Resolutions)

• The prognosis of Malignant Mesothelioma of Pleura is generally poor. Death mostly occurs due to spread of cancer, large size of tumor, or severely affected function of the lung
• The mean survival period following diagnosis of the tumor is around 1.5 years; some individuals are known to survive for a longer time period
• Nevertheless, the prognosis depends on a combination of factors, such as:
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • Grade of the tumor: It is considered as a helpful parameter in predicting the prognosis
  • Cell growth rate of the cancer (its ki-67 value): The ki-67 value is based on a protein found in cells that is a good indicator of how fast the tumor cells are growing. The ki-67 value is determined by a pathologist and is usually mentioned in the pathology report
  • Response to treatment and medical therapy: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
  • The size of the tumor and the extent of its invasion: Individuals with small-sized tumors fare better than those with large-sized tumors
  • Stage of cancer per FIGO (or TNM): With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
  • Individuals with bulky disease have a poorer prognosis
  • Involvement of the regional lymph nodes, which can adversely affect the prognosis
  • Involvement of vital organs may complicate the condition
  • The surgical respectability of the tumor (meaning, if the tumor can be removed completely): Stage I to stage III tumors are generally resectable
  • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
  • Progression of the condition makes the outcome worse

Factors that generally favor positive outcomes include the following:

• Lower stage tumors
• Younger age and good health status of the individual
• Female gender
• Normal blood cell count and normal levels of lactating dehydrogenase (LDH) in blood
• Absence of chest pain and of any significant weight loss
• Epithelial type of Pleural Mesothelioma

Additional and Relevant Useful Information for Malignant Mesothelioma of Pleura:

Asbestos exposure may not always cause a malignant process in the body. But, in addition to malignancy, it can also cause the following conditions:

• Benign pericardial effusion
• Benign peritoneal effusion
• Benign pleural effusion
• Diffuse pericardial thickening
• Diffuse peritoneal thickening
• Diffuse pleural thickening
• Idiopathic pulmonary fibrosis
• Pericardial calcification
• Pericardial plaque
• Peritoneal plaque
• Pleural plaque