All About Mesothelioma

Carolyn Vachani, MSN, RN, AOCN and Charles B. Simone II, MD
Updated by: Christina Bach, MBE, MSW, LCSW, OSW-C
OncoLink
Last Modified: January 19, 2016

What is mesothelial tissue?

The mesothelium is a protective sac that covers and protects most internal organs in the body. It is composed of two layers, one layer covers the organ and the second layer forms a sac around it. The mesothelium produces a lubricating fluid that is released between these layers, allowing moving organs (such as the lungs) to move easily. This area, between the two layers around the lungs is called the pleural space. Mesothelial tissue is found lining the abdominal cavity organs, lungs, testes and heart.

What is mesothelioma?

Mesothelioma occurs when the mesothelial cells grow out of control. These cells also lose the ability to stop producing the lubricating fluid when there is enough. This results in the unwanted encasement of organs within a thick rind of tumor tissue and excess fluid buildup, ultimately causing symptoms. These cells can grow and invade other organs, or spread to other areas of the body. When the cells spread to other areas of the body, it is called metastasis.

The majority of mesotheliomas are found in the lining of the lung (approximately 70%). About 20-30% percent of cases are found in the abdominal cavity lining (peritoneal mesothelioma), and even more rarely, mesothelioma is found in the lining of the heart (1-2%) or testicles.

What causes mesothelioma and am I at risk?

Mesothelioma is a rare cancer, with approximately 2,500-3,000 cases diagnosed each year in the United States. The biggest risk factor for developing the disease is exposure to asbestos, accounting for 50 to 80 percent of all cases. Asbestos has been used in many products, including cement, brake linings, roof shingles, flooring products, textiles, and insulation. Particles can be released from these products, particularly during the manufacturing process, and inhaled. Prior to knowing the dangers, asbestos miners and other workers exposed to asbestos worked without wearing any protection. Since the 1970s, the U.S. Occupational Safety and Health Administration (OSHA) has set limits for acceptable levels of asbestos exposure and requires protective equipment in the workplace. Family members of people who worked with asbestos were also exposed to the toxin when it was carried home on clothing and hair, putting them at increased risk for mesothelioma. It is five times more common in men, which is due in most part to work-related exposure to asbestos. Risk also increases with age.

Veterans who served in mining, milling, shipyard work, insulation work, demolition of old buildings and other construction settings, and in countries where asbestos is still present in buildings that may have been damaged in combat are also at a higher risk to develop mesothelioma. Veterans with a diagnosis of mesothelioma may file a service claim for disability compensation if they believe their diagnosis is a direct result of service connected asbestos exposure. These cases are determined on a case by case basis, but decisions can greatly impact your access to and the payment for medical care for mesothelioma.

While up to 80% of cases of pleural mesothelioma occur in individuals who have had known asbestos exposure, only 10% of those with a history of heavy exposure actually develop the disease. This suggests that additional exposures or factors are involved to actually develop the disease. Even more puzzling is the fact that only 50% of people with peritoneal mesothelioma have a history of asbestos exposure.

It takes 20 to 50 years from the time of asbestos exposure until mesothelioma is detected. Although most individuals who develop mesothelioma had a repeated exposure to asbestos over many years or longer, some develop the cancer with as little as one or two months of asbestos exposure. The incidence of mesothelioma varies in different areas of the world, depending on when asbestos was widely used in that area. Rates are higher in the United Kingdom, where about 1800 cases per year are diagnosed. The incidence takes into consideration the number of cases and the size of the population. This is because asbestos use in Western Europe remained high until 1980, whereas maximum exposure in the U.S. was from the 1930s to 1960s. Australia was one of the world's largest producers of asbestos, leading to the country having the highest rates worldwide (based on the size of the population). Rates in the U.S. are beginning to decline, whereas rates in Europe and Australia are expected to plateau in the next 10-15 years, before declining.

Following the ban of asbestos in many countries, asbestos producers started to promote the sale of their product to developing countries, such as Asia and Latin America. Experts fear that the peak rates in these areas are yet to come, and will mimic what has been seen in the U.S. and Europe. As asbestos is widely available, even today, in China and India, rates in those countries are projected to increase significantly over the next two decades.

Other risk factors include prior radiation therapy to the chest, collapsotherapy (for the treatment of tuberculosis), and potentially even exposure to certain viruses or zeolites (minerals that have a chemical similarity to asbestos such as erionite). Erionite is a known human carcinogen and is common in rocks and soil in certain geographic areas. Higher mesothelioma incidence in these areas is thought to be caused by increased exposure to erionite. Smoking does not seem to increase the risk of developing the disease.

How can I prevent mesothelioma?

By decreasing exposure to asbestos, the risk of mesothelioma is decreased. Workers who are exposed to asbestos on the job should wear protective clothing and masks. These workers should change their clothing before leaving the work site to avoid carrying any particles home. OSHA has set standards regulating these procedures.

Screening for Mesothelioma

There is no good screening test for mesothelioma. Radiologic studies (x-ray, CT scan) are not sensitive enough to detect tumors before symptoms occur. Currently, researchers are investigating the use of several blood markers in an attempt to detect mesothelioma earlier than conventional methods for people with a history of asbestos exposure. These tests include measurements of serum osteoporin, levels of the soluble mesothelin-related protein, and the Mesomark assay that evaluates the levels of soluble mesothelin-related proteins released by mesothelioma cells. Presently, however, all of these tests are considered experimental.

What are the signs of mesothelioma?

The symptoms of mesothelioma are often caused by a build-up of tumor tissue surrounding the lung and accumulation of fluid in the pleural space, which prevents the lung from expanding fully. This causes pressure on the lung, leading to pain and shortness of breath. As the disease progresses, patients may lose weight and have a dry, hacking cough. Mesothelioma originating in the pleura can directly spread into the abdomen. Mesothelioma can also originate in the peritoneal tissue of the abdomen. Symptoms most commonly associated with abdominal disease include abdominal swelling, pain and weight loss.

How is mesothelioma diagnosed?

Patients who present with symptoms worrisome for mesothelioma often initially have a chest x-ray done that shows a build-up of fluid in the lining of the lung. These patients then undergo a CT scan of the chest to further evaluate the cancer. In the case of abdominal mesothelioma, a CT scan is obtained to visualize the anatomy in the abdomen.

The fluid in the lining of the lung is often drained by a procedure called a thoracentesis. This can improve symptoms. A diagnosis of mesothelioma can sometimes be made by looking at the cells of this fluid under the microscope. If a diagnosis is not possible with the fluid alone, patients would then undergo a pleural biopsy to have the diagnosis confirmed. In the lung, a thoracoscope is used to go through the chest wall, between the ribs, to obtain a sample of the tissue. A peritoneoscope or abdominal laparoscopy are used to enter the abdomen to obtain a tissue sample to diagnose abdominal mesothelioma.

How is mesothelioma staged?

Staging is done to determe the extent of the disease, and the stage then dictates the treatment. Recommend tests for staging mesothelioma include chest and abdominal CT with contrast and possible chest MRI or VATS (thoracoscopic biopsy), which can also evaluate lymph nodes and other tissues. A pathologist will also exam the cells/tissues obtained to determine the subtype of mesothelioma cells present in the tumor. There are three types, epithelioid, sarcomatoid and biphasic (mixed). The cell subtype can influence treatment decisions together with staging.

Providers then use the TNM system (also called tumor - node - metastasis system). This describes the size and local spread of the tumor (T), if any lymph nodes are involved (N), and if it has spread to other more distant areas of the body (M). This is then converted to a stage, between 0 and IV (four), with higher numbers denoting more advanced disease. Patients with earlier stage tumors tend to live longer and respond better to available treatments. 

International Mesothelioma Interest Group (IMIG) Staging System for Diffuse Malignant Pleural Mesothelioma (American Joint Committee on Cancer, 7th Edition, 2010)

*There is currently no standard staging system for peritoneal mesothelioma.

The TNM breakdown is quite technical, but is provided here for your reference. Your healthcare provider will use the results of the diagnostic work up to assign the TNM result.

Primary Tumor (T)

TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor limited to the ipsilateral parietal pleura with or without mediastinal pleura and with or without diaphragmatic pleural involvement
T1a No involvement of the visceral pleura
T1b Tumor also involving the visceral pleural
T2 Tumor invading each of ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following:
  • Involvement of the diaphragmatic muscle
  • Extension of tumor from visceral pleura into the underlying pulmonary parenchyma
T3 Locally advanced but potentially resectable tumor.  Tumor involving all of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura), with at least one of the following:
  • Involvement of the endothoracic fascia
  • Extension into the mediastinal fat
  • Solitary, completely resectable focus of tumor extending into the soft tissues of the chest wall
  • Nontransmural involvement of the pericardium
T4 Locally advanced technically unresectable tumor.  Tumor involving all of the ipsilateral pleural services (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following
  • Diffuse extension or multifocal masses of tumor in the chest wall, with or without associated rib destruction
  • Direct transdiaphragmatic extension of the tumor to the peritoneum
  • Direct extension of the tumor to the contralateral pleura
  • Direct extension of the tumor to the mediastinal organs
  • Direct extension of tumor into the spine
  • Tumor extending through to the internal surface of the pericardium with or without a pericardial effusion or tumor involving the myocadium

Regional Lymph Nodes (N)

NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis to the ipsilateral bronchopulmonary or hilar lymph nodes
N2 Metastases in the subcarinal lymph node or the ipsilateral mediastinal lymph nodes including the ipsilateral internal mammary and peridiaphragmatic nodes
N3 Metastasis in contralateral mediastinal, contralateral internal mammary, ipsilateral or contralateral supraclavicular lymph nodes

Distant Metastasis (M)

M0 No distant metastasis
M1 Distant metastasis

Stage Grouping           

Stage T N M
I T1 N0 M0
IA T1 N0 M0
IB T1b N0 M0
II T2 N0 M0
III T1, T2 N1 M0
  T1, T2 N2 M0
  T3 N0,N1,N2 M0
IV T4 Any N M0
  Any T N3 M0
  Any T Any N M1

How is mesothelioma treated?

Treatment is dependent on the stage of the disease, the location of the tumor, the patient's age, and his or her state of health. The first step to deciding on treatment is to determine if the disease is operable - meaning can surgery be performed and be beneficial to the patient? Younger, healthy patients with early-stage malignant pleural mesothelioma may be candidates for surgery that removes the mesothelial tissue around the tumor. Surgery to either remove the entire lung with the tumor (termed extrapleural pneumonectomy) or lung-sparing surgery that removes only the tumor and the lining of the lung (termed extended or radical pleurectomy), is the most common option for these patients.

Similar comprehensive surgery is often considered in patients with peritoneal mesothelioma. In addition, patients with peritoneal mesothelioma may also receive intraperitoneal chemotherapy (chemotherapy delivered directly into the peritoneal space) with surgery. This has been shown to improve survival in patients with peritoneal mesothelioma.

All of these definitive thoracic or peritoneal surgeries are extensive. Many patients are not able to undergo surgery due to having advanced disease at diagnosis or not being able to tolerate the surgery due to their health. 

For patients that have surgery to remove the entire lung, radiation therapy is commonly given after surgery to kill any remaining cancer cells not removed by surgery. Radiation therapy after lung-sparing surgery, however, is not routinely given. The radiation can damage the remaining healthy lung tissue and result in toxicity that outweighs any benefit of radiotherapy. Radiation therapy is often delivered to surgical incision sites to prevent the cancer from recurring in that area. In patients who do not undergo surgery, radiation therapy may be given to treat problem areas with the goal of relieving symptoms, like pain or trouble breathing.

Chemotherapy is also a standard treatment for mesothelioma and can provide significant relief of symptoms. Chemotherapy can be given before, after, or without surgery. Agents that are used, either alone or in combination, include: cisplatin, carboplatin, doxorubicin, pemetrexed, gemcitabine, and vinorelbine.

Symptom management and supportive care

People with mesothelioma may encounter a recurring build-up of fluid in the pleural space. This fluid can be removed with a pleural catheter (a tube that is put into the chest wall and left in to allow the fluid to be drained when needed) or a procedure called thoracentesis (a small needle is put through the chest wall into the pleural space, the fluid is drained, and the needle is removed). In many cases, this will be followed by a procedure called pleurodesis, in which a medication (i.e. talc, bleomycin) is injected into the lung to create scar tissue in the hopes of decreasing future fluid from developing.

In the abdomen, the procedure to remove fluid is called paracentesis. In this procedure, a needle is inserted through the abdomen into the fluid filled space, and the fluid is drained. If this is a chronic problem, patients may have a catheter placed, allowing them to drain the fluid themselves at home as needed. Removal of the fluid alleviates the difficulty breathing and pain that is caused by fluid build-up.

Your healthcare team will also work to manage other symptoms, including pain and nausea and vomiting you may experience as a result of your diagnosis and treatment. These symptoms can be managed through a combination of medical treatments (i.e. pain medications, anti-nausea medication, and counseling) and complimentary/integrative therapies (i.e. yoga, mindfulness, reiki and massage).

Clinical Trials

Because the current therapies have limited effectiveness, researchers are continuing to look for new ways to treat mesothelioma. Some of the treatments being investigated include immunotherapy, gene therapy (a method that attempts to correct the abnormal gene that causes the cancer to grow out of control), chemotherapy administered directly into the pleural space, and intraoperative Photodynamic Therapy (PDT- a treatment that uses a laser to activate a photosensitizing drug during the surgical removal of the cancer in an attempt to kill any remaining cancer cells not removed by surgery). Patients should talk with their healthcare team about current clinical trials for mesothelioma.

Follow-up care and survivorship

Your healthcare team will provide regular physical examinations and surveillance imaging throughout your treatment for mesothelioma. 

Fear of advanced illness, anxiety, advanced care planning, the financial impact of cancer treatment, legal and employment issues, and coping strategies are common emotional and practical issues experienced by people with mesothelioma. Your healthcare team can identify resources for support and management of these practical and emotional challenges faced during and after cancer.

Cancer survivorship is a relatively new focus of oncology care. With some 15 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink.

Resources for more information

National Comprehensive Cancer Network Guidelines for Patients www.nccn.org/patients/guidelines/mpm/index.html

Department of Veterans Affairs www.publichealth.va.gov/exposures/asbestos/

The Meso Foundation (formerly the Mesothelioma Applied Research Foundation) www.curemeso.org/site/c.duIWJfNQKiL8G/b.8598593/k.D685/Homepage.htm

This nonprofit organization's website is a great resource for patients, families & healthcare professionals.

References

http://www.cancer.org/cancer/malignantmesothelioma/detailedguide/malignant-mesothelioma-key-statistics

National Comprehensive Cancer Network Practice Guidelines in Oncology http://www.nccn.org/professionals/physician_gls/pdf/mpm.pdf (for healthcare professionals; registration required)

Carbone, M. et al., (2011). Erionite exposure in North Dakota and Turkish villages with mesothelioma. In Proceedings of the National Academy of Sciences of the United States of America. Proceedings of the National Academy of Sciences of the United States of America. pp. 13618–13623.

Carbone, Michele, Bevan H. Ly, Ronald F. Dodson, Ian Pagano, Paul T. Morris, Umran A. Dogan, Adi F. Gazdar, Harvey I. Pass, and Haining Yang.(2012). Malignant mesothelioma: facts, myths, and hypotheses. Journal of Cellular Physiology,227(1), 44-58.

Friedberg, J. S., Culligan, M. J., Mick, R., Stevenson, J., Hahn, S. M., Sterman, D., ... & Cengel, K. (2012). Radical pleurectomy and intraoperative photodynamic therapy for malignant pleural mesothelioma. The Annals of Thoracic Surgery, 93(5), 1658-1667.

Helm, J.H., Miura, J.T., Glenn, J.A., (...), Turaga, K.K., Johnston, F.M. (2015). Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma: A Systematic Review and Meta-analysis. Annals of Surgical Oncology 22(5), 1686-1693.

Hubert, J., Thiboutot, E., Dubé, P., (...), Drolet, P., Sideris, L.(2015). Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with oxaliplatin for peritoneal mesothelioma: Preliminary results and survival analysis.  Surgical Oncology, 24(1), 41-46.

Husain, A. N., Colby, T., Ordonez, N., Krausz, T., Richard Attanoos MB, B. S., Beasley, M. B., ... & Churg, A. (2013). Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group. Archives of Pathology & Laboratory Medicine, 137(5), 647.

Kindler, H. L., Karrison, T. G., Gandara, D. R., Lu, C., Krug, L. M., Stevenson, J. P., ... & Albain, K. S. (2012). Multicenter, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin plus bevacizumab or placebo in patients with malignant mesothelioma. Journal of Clinical Oncology, 30(20), 2509-2515.

Lang-Lazdunski, L., Bille, A., Lal, R., Cane, P., McLean, E., Landau, D., ... & Spicer, J. (2012). Pleurectomy/decortication is superior to extrapleural pneumonectomy in the multimodality management of patients with malignant pleural mesothelioma. Journal of Thoracic Oncology, 7(4), 737-743.

Rosenzweig, K. E., Zauderer, M. G., Laser, B., Krug, L. M., Yorke, E., Sima, C. S., ... & Rusch, V. (2012). Pleural intensity-modulated radiotherapy for malignant pleural mesothelioma. International Journal of Radiation Oncology, Biology and, Physics, 83(4), 1278-1283.

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