Overview of Malignant Mesothelioma

Symptoms, risk factors, and diagnosis of malignant mesothelioma

Overview of Mesothelioma

Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor 8/2018

Malignant pleural mesothelioma is an uncommon type of cancer that begins in the mesothelial cells of the pleura. The pleura is a thin membrane that surrounds the lungs and lines the chest cavity. The pleura consists of a visceral surface, which covers the lungs and a parietal surface, which lines the walls of the chest cavity and covers the upper surface of the diaphragm and lungs. The two layers are one continuous sheet of tissue that contains mesothelial cells. There is normally a very small amount of watery fluid within the pleural cavity that lubricates the pleural surfaces and allows the lungs to move freely over the inner surface of the chest wall during breathing.

Malignant pleural mesothelioma is a rare and aggressive cancer that represents about 90 percent of all malignant mesothelioma cases. It’s primarily caused by the inhalation of asbestos, a fiber commonly found in some forms of insulation, vinyl floor tiles, and other material. Tumors form in the pleura, a thin membrane of cells that line the lungs and chest wall.

Malignant pleural mesothelioma is predominantly caused by exposure to asbestos. The association between inhaled asbestos particles and mesothelioma was recognized in 1960.(1)Asbestos exposure is also associated with:

  • A non-cancerous scarring of the lungs called “asbestosis,” and
  • Developing lung cancer, which is worsened by cigarette smoking.

Types of Malignant Pleural Mesothelioma

Doctors classify pleural mesothelioma into 3 distinct categories: epithelioid, sarcomatoid, and mixed-type. Epithelioid is the most common, occurring in 60-70% of patients. However, it may be confused with another type of lung cancer called adenocarcinoma; therefore, special tests are necessary to confirm a diagnosis. The sarcomatoid type (10-20%) is the least common and most aggressive. Mixed-type (20-30%) shows features of both epithelioid and sarcomatoid. Before considering treatment options, patients must have a confirmed diagnosis of mesothelioma and accurate staging of the disease performed.(1)

Signs and Symptoms of Malignant Pleural Mesothelioma

The majority of patients with malignant pleural mesothelioma experience shortness of breath and a third of patients experience chest pain. Patients may also experience weight loss, cough, weakness, fever, and loss of appetite. A pleural effusion (fluid between the lungs and chest wall) is also present in the majority of patients. Most patients have a significant history of asbestos exposure, which occurred 30-40 years prior to exhibiting signs of the disease. Men are three times more likely to have the disease than women because of work related exposure in high-risk occupations, such as mining, manufacturing, and ship construction.(1)

Other Signs and Symptoms of Mesothelioma

  • Persistent cough
  • Shortness of breath
  • Chest discomfort or pain
  • Trouble breathing
  • Wheezing
  • Blood in sputum (mucus coughed up from the lungs)
  • Hoarseness
  • Loss of appetite
  • Fatigue
  • Difficulty swallowing
  • Weigh loss
  • Loss of appetite

Diagnosis & Tests For Malignant Mesothelioma

Determining the presence of malignant pleural mesothelioma and the type of mesothelioma requires examination of tissues removed from the lung. Tissue examination confirms the diagnosis and can be evaluated for biomarkers that may help direct treatment with precision cancer medicines. Sometimes this can be accomplished by looking for cancer cells in the sputum or by the removal of fluid from a pleural effusion (thoracentesis) for evaluation under a microscope. More commonly however, a biopsy which is the removal of a small piece of tissue for examination under a microscope is required. While there was once a concern that needle biopsy could spread the cancer, research indicates that a needle biopsy of the pleura is a safe procedure and it detects malignant mesothelioma approximately 86% of the time.(1) A biopsy can be obtained using one or more of the following procedures.

  • CT Guided Fine Needle Aspiration Biopsy: CT guided fine needle aspiration biopsy is the most common way to evaluate possible cancers. A CT scan takes a very detailed picture of a patient’s suspected cancer, allowing the insertion of a thin needle to remove a sample of the tissue. This gives doctors the most information without resorting to a more invasive surgery (thoracotomy) and direct biopsy.(2,3)
  • Thoracotomy: During a thoracotomy, a surgeon makes a large incision in a patient’s chest in order to directly access the mass and directly remove part or all of the suspicious area. In some patients with a peripheral lung mass and no evidence of mediastinal or systemic cancer, a wedge resection of the lesion is sometimes performed and diagnosis made on a frozen-section of tissue. If lung cancer is confirmed, a formal cancer resection is then performed.
  • Endoscopic Ultrasound Guided Fine Needle Aspiration Biopsy: The mediastinum is the area behind the breast bone and consists of blood vessels, lymph nodes and other structures. Because lung cancer frequently spreads to lymph nodes in the mediastinum, biopsies to this area are often necessary. An endoscopic ultrasound guided fine needle aspiration biopsy is often used to evaluate the mediastinum. This technique is performed in order to avoid the more invasive procedures of mediastinoscopy or thoracotomy. Using this technique, more invasive methods of diagnosis can be avoided in approximately 50% of patients. An ultrasound machine is used to take pictures of the mediastinum, allowing a small biopsy needle to be directly inserted into the suspicious area without making an incision in the chest.
  • Cervical Mediastinoscopy: Mediastinoscopy is another diagnostic procedure used to determine whether mediastinal lymph nodes contain cancer. This procedure is used in cases where endoscopic ultrasound guided fine needle aspiration biopsy is not indicated or was not successful. Medianstinoscopy requires general anesthesia, a small anterior neck incision and insertion of an endoscope, which is a thin, lighted tube. A complete procedure includes extensive sampling of lymph nodes in the upper and lower mediastinum.
  • Bronchoscopy: During a bronchoscopy, a physician inserts a bronchoscope (thin, lighted tube) through the nose or mouth into the trachea (windpipe) and bronchi (air passages that lead to the lung). Through this tube, the surgeon can examine the inside of the trachea, bronchi and lung and collect cells or small tissue samples.
  • Thorascopy: During this procedure, an endoscope called a thorascope is inserted through a small incision in the chest wall. Thorascopy is a limited surgical procedure that allows the lining of the chest wall and the lungs to be examined and biopsied to determine if cancer is present.
  • Sputum Cytology: Sputum cytology is a procedure used to examine mucus that is coughed up from the lungs or breathing tubes. The mucus is examined under a microscope in order to detect cancer cells.
  • Thoracentesis: During a thoracentesis, a needle is inserted through the chest wall into the pleural space in order to remove a sample of the fluid that surrounds the lungs in order to check for the presence of cancer cells.

Staging Tests for Mesothelioma

Following a tissue diagnosis of mesothelioma, it is important to accurately determine the stage of cancer in order to begin treatment planning.

The stage describes how far the cancer has spread and each stage of cancer may be treated differently. There are many staging systems, but TNM is the most common. “T” refers to the size of the tumor, “N” to the number of lymph nodes involved, and “M” to metastasis. TNM staging measures the extent of the disease by evaluating these three aspects and assigning a stage, which is usually between 0-4. Generally, the lower the stage, the better the treatment prognosis (outcome) is.

A new international staging system for malignant pleural mesothelioma that is TNM-based was created in June 1994 at the Seventh World Conference of the International Association for the Study of Lung Cancer. There are currently six stages of malignant pleural mesothelioma: IA, IB, II, III, IV and Occult. While a higher stage number generally correlates with a worse prognosis, this system is relatively new and outcomes cannot be predicted with certainty. Determining mesothelioma stage requires obtaining a sample of lung and lymph nodes, which is typically performed during thoracentesis, and evaluating them under a microscope.(4)

Once cancer has been diagnosed, a careful evaluation will be made to determine how far the cancer has spread (also called stage). In order to begin evaluating and discussing treatment options with their healthcare team, patients need to know the correct stage of their cancer. The following tests may be performed to accurately stage mesothelioma:

  • Chest x-ray: A chest radiograph may show pleural effusions or pleural thickening.
  • Computed tomography (CT): A CT scan may show whether there is fluid, thickening, or irregularities in the pleural. CT may also be helpful for determining whether the cancer has spread beyond the pleura into the chest wall, pericardium (sack around the heart), diaphragm (breathing muscle), or the lymph nodes.
  • Magnetic resonance imaging (MRI): An MRI scan can be particularly useful to determine how extensive the cancer is and whether it can be removed with surgery. In addition to identifying the extent and whether the cancer can be removed with surgery, a special type of MRI, called contrast-enhanced MRI, is also helpful for differentiating mesothelioma from other types of cancer.3
  • Positron emission tomography (PET): Unlike techniques that provide anatomical images, such as X-ray, CT and MRI, PET shows chemical and physiological changes related to metabolism. This is important because these functional changes often occur before structural changes in tissues. PET images may therefore show abnormalities long before they would be revealed by X-ray, CT, or MRI. PET can sometimes distinguish between malignant and non-malignant fibrous processes in the pleura.3
  • Bone Scan: A bone scan is used to determine whether cancer has spread to the bones. Prior to a bone scan, a surgeon injects a small amount of radioactive substance into a vein. This substance travels through the bloodstream and collects in areas of abnormal bone growth. An instrument called a scanner measures the radioactivity levels in these areas and records them on x-ray film.

Stages of Mesothelioma

Stage I-III Pleural Mesothelioma

Patients with stage I-III disease have cancer that can potentially be removed with surgery.

Stage IA: Patients with stage IA disease have cancer limited to the pleura on one side of the chest with no involvement of lymph nodes and no spread to other sites.

Stage IB: Patients with stage IB disease have cancer that has spread to the parietal pleura, including mediastinal and diaphragmatic pleura on one side of the chest and can have scattered foci of tumor also involving the visceral pleura. There is no involvement of lymph nodes or distant spread.

Stage II: Patients with stage II disease have cancer involving both parietal and visceral pleura and can have involvement of diaphragmatic muscle or extension into the lung. There can be lymph node involvement, but there is no distant spread.

Stage III: Patients with stage III cancer have locally advanced but potentially surgically resectable cancer. They have cancer involving parietal, mediastinal, diaphragmatic, and visceral pleura. They can also have spread to fascia, mediastinal fat, and soft tissue of the chest wall or involvement of the pericardium. These patients can have spread to the bronchopulmonary or hilar lymph nodes or to subcarinal or mediastinal lymph nodes, including the internal mammary nodes. They do not have spread to the opposite side of the chest or distant metastasis.

Stage IV Pleural Mesothelioma

Patients with stage IV disease have cancer that cannot be typically removed with surgery. They have spread of cancer to the mediastinal, internal mammary or supraclavicular lymph nodes on the side of the chest opposite to the original cancer. Distant metastasis can also be present.

Recurrent Pleural Mesothelioma

Patients with recurrent cancer have disease recurrence after primary treatment or failed primary treatment.

Screening & Prevention of Malignant Mesothelioma

Information about the prevention of cancer and the science of screening appropriate individuals at high-risk of developing cancer is gaining interest. Physicians and individuals alike recognize that the best “treatment” of cancer is preventing its occurrence in the first place or detecting it early when it may be most treatable.(5,6)

The chance of an individual developing cancer depends on both genetic and non-genetic factors. A genetic factor is an inherited, unchangeable trait, while a non-genetic factor is a variable in a person’s environment, which can often be changed. Non-genetic factors may include smoking, diet, exercise, or exposure to other substances present in our surroundings. These non-genetic factors are often referred to as environmental factors. Some non-genetic factors play a role in facilitating the process of healthy cells turning cancerous (i.e. the correlation between smoking and lung cancer) while other cancers have no known environmental correlation but are known to have a genetic predisposition. A genetic predisposition means that a person may be at higher risk for a certain cancer if a family member has that type of cancer.

Heredity or Genetic Factors

There does not appear to be a hereditary risk for individuals developing mesothelioma

Environmental or Non-Genetic Factors

Mesothelioma is primarily associated with environmental factors, especially exposure to asbestos and smoking.(3

Asbestos: Asbestos is the general name applied to a group of naturally occurring minerals that form fibers. These asbestos fibers have been used in a variety of applications such as textiles, cement, paper, wicks, ropes, floor and roofing tiles, water pipes, wallboard, fireproof clothing, gaskets and brake linings.

Asbestos fibers easily break into particles. When inhaled, these dust particles can lodge in the lungs and cause damage that leads to an increased risk of lung cancer. It is estimated that since the beginning of World War II, approximately 8 million people have been exposed to asbestos in the workplace. Approximately 5% of the lung cancer cases diagnosed each year are caused by asbestos.

Asbestos increases the risk of developing mesothelioma. Mesothelioma can result from neighborhood or environmental exposure to asbestos, occupational exposure, and household contact with asbestos dust. The rates of mesothelioma peaked for individuals born around 1910 and have steadily declined over time. Currently, there are about 2,000 cases of mesothelioma each year. This is primarily an asbestos-related cancer; only a fraction of mesothelioma cases are unrelated to asbestos exposure. Individuals involved in shipbuilding during World War II have an increased risk of mesothelioma. In fact, several shipbuilding areas such as Virginia, England, Wales and Japan, have higher rates of mesothelioma. In addition, workers who are heavily exposed to asbestos bring the dust into their homes on their clothing, hair and skin, thus exposing their family members and placing them at a higher risk of developing mesothelioma. Smoking does not appear to increase the risk of developing mesothelioma.

Clinical studies have demonstrated that individuals who are exposed to large amounts of asbestos have a 5 times greater chance of developing lung cancer than individuals who have not been exposed.

Cigarettes: Individuals who smoke and are exposed to asbestos have an even greater risk of developing mesothelioma. Studies show that smokers who are exposed to asbestos are 90 times more likely to develop lung cancer than individuals who do not smoke and have not been exposed to asbestos.

There is also large body of research that indicates that individuals who smoke are at a significantly increased risk of developing lung cancer. Approximately 85% of the lung cancer cases diagnosed each year can be associated with smoking. Over time, carcinogens in cigarettes damage the cells in the lungs and eventually, these damaged cells may become cancerous. Several factors contribute to a smoker’s risk of developing lung cancer, such as the age at initiation of smoking, the number of years smoked, the depth of inhalation, and the number of cigarettes smoked daily.

Cigars and Pipes: Individuals who smoke cigars or pipes appear to be at an increased risk of developing lung cancer, although this risk appears lower than that of cigarette smokers. Again, the number of years smoked, the amount smoked and the depth of inhalation all play a role in whether or not lung cancer will develop. Researchers have speculated that the reason for the decreased risk among cigar and pipe smokers when compared with cigarette smokers may be that cigar and pipe smokers do not inhale as deeply as cigarette smokers because cigar smoke tends to be more irritating. Cigar smokers also tend to smoke less each day, as it takes about 1-2 hours to completely smoke a cigar, whereas it takes less than 10 minutes to smoke a cigarette.

Radon: Radon is a carcinogen that can cause damage to the lungs that may eventually lead to lung cancer. It is estimated that radon is responsible for about 10% of the lung cancer cases diagnosed each year. Individuals who smoke and are exposed to radon are at an even higher increased risk of developing lung cancer. Most of the cancer deaths associated with radon occur among smokers.

Radon is a naturally occurring, invisible radioactive gas. It is present in soil and rocks and can seep into homes and other buildings. In situations where ventilation is restricted, radon can accumulate in the atmosphere and lead to higher levels of exposure. Individuals who work in mines are often exposed to higher concentrations of radon than the general population. However, radon can also be present in many homes. Some geographic areas have higher concentrations of radon, but radon can also seep into homes in geographic areas that are not considered high risk. When ventilation is restricted in basements in order to conserve energy, radon can seep from the soil into the basement and accumulate in the poorly ventilated area.

Prevention

Cancer is largely a preventable illness. Two-thirds of cancer deaths in the U.S. can be linked to tobacco use, poor diet, obesity, and lack of exercise. All of these factors can be modified. Nevertheless, an awareness of the opportunity to prevent cancer through changes in lifestyle is still under-appreciated.(5,6)

Nearly everyone has been exposed to asbestos at some point. Asbestos is widely used and small amounts may be found in a variety of products. In addition, the breakdown of asbestos products as well as natural deposits of the fiber can cause the release of asbestos particles into the environment.

Three agencies are responsible for regulating the use of asbestos products and the exposure caused to the general public. The Environmental Protection Agency (EPA) regulates asbestos in buildings, drinking water and the environment. The Consumer Product Safety Commission (CPSC) regulates asbestos in consumer products. The Food and Drug Administration (FDA) monitors asbestos contamination in food, drugs and cosmetics.

Still, individuals may be exposed to asbestos at work or in other environments. The Occupational Safety and Health Administration (OSHA) has issued regulations for employers regarding the treatment of asbestos exposure in the workplace. In addition, the Mine Safety and Health Administration (MSHA) regulates mine safety. Often, workers are provided with protective equipment and instructions regarding work practices and safety procedures. Individuals concerned about asbestos exposure at work may wish to discuss safety precautions with their employers or request information from OSHA. Individuals who are or have been exposed to asbestos should refrain from smoking.

Screening and Early Detection

For many types of cancer, progress in the areas of cancer screening and treatment has offered promise for earlier detection and higher cure rates. The term screening refers to the regular use of certain examinations or tests in persons who do not have any symptoms of a cancer but are at high risk for that cancer.

Several key organizations now recommend screening for lung cancer with helical low-dose computed tomography (LDCT) for selected patients at high risk of developing the cancer.

These recommendations were largely based on results from The National Lung Screening Trial (NLST). The NLST enrolled current and former heavy smokers and screened them annually with either chest x-rays or low-dose spiral CT. People in the CT group were 20% less likely to die of lung cancer.

Low-dose CT scans are a special type of imaging scan that can identify smaller nodules than chest x-rays, making them a strong candidate for lung cancer screening. Although low-dose CT scans can detect lung cancer early, they also can have false-positive results, which means they may not be appropriate for standard use because false-positive results can lead to unnecessary invasive procedures that can have deadly complications. However, in high-risk populations—such as older individuals who are current or former smokers—the benefits of screening with low-dose CT scans appears to outweigh the harms.

The guidelines recommend that smokers and former smokers ages 55 to 74 who have smoked for 30 pack years or more and either continue to smoke or have quit within the past 15 years should undergo annual screening with low-dose CT scan.(5,6)

References

[1] Antman KH, Pass HI, DeLaney T, et al. Benign and malignant mesothelioma. In: Devita VT Jr, Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 4th Edition Philadelphia, PA:JB Lippincott Co;1993:1489-1508.

[2] Ruffie P, Feld R, Minkin S, et al. Diffuse Malignant Mesothelioma of the Pleura in Ontario and Quebec: A Retrospective Study of 332 Patients. Journal of Clinical Oncology 1989;7:1168-1168.

[3] Adams RF, Gray W, Davies RJ, et al. Percutaneous image-guided cutting needle biopsy of the pleura in the diagnosis of malignant mesothelioma. Chest. 2001;120:1798-802.

[4] Rusch VW. A Proposed New International TNM Staging System for Malignant Pleural Mesothelioma. Chest 1995;108:1122-1128.

[5] Eibel R, Tuengerthal S, Schoenberg SO. The Role of New Imaging Techniques in Diagnosis and Staging of Pleural Mesothelioma. Current Opinion in Oncology. 2003;15:131-138.

[6] cancer.gov/types/lung/patient/lung-prevention-pdq#section/_12

Comments