What is mesothelioma?

Related conditions:
Lung cancer, pericardial effusion

Definition:
Mesothelioma is a rare cancer of the mesothelium, the collective name for the membranes that surround the body’s internal organs. Particular mesothelia—the pleura (which covers the lungs), the peritoneum (which lines the abdominal cavity), and the pericardium (the sac that surrounds the heart)—lend their names to forms of mesothelioma. Pleural mesothelioma and peritoneal mesothelioma are the most common forms. At the cellular level, mesothelioma takes three main forms: epithelioid (50 to 70 percent of cases), in which the cancer cell is typically uniform and cube shaped, with a visible nucleus; sarcomatoid (7 to 20 percent), in which the cells are more irregular and oval shaped, with less visible nuclei; and biphasic (20 to 35 percent), a mixture of the two.

Risk factors: About 80 percent of cases strike those exposed to
asbestos, a name that refers to six silicate minerals: the serpentine mineral chrysotile and the amphibole minerals actinolite, amosite, anthophyllite, crocidolite, and tremolite. These minerals were heavily used in many industries and products from the late nineteenth century to the 1980s. Today, although more strictly regulated, they remain components of materials for roofing, thermal and electrical insulation, cement pipe and sheets, flooring, gaskets, friction materials, coatings, plastics, textiles, paper, and other products. Those who work with these materials in asbestos mining and milling, shipyards, building demolition, heating and insulation, brake repair, and asbestos abatement as well as family members exposed to their clothing, are at risk.

Etiology and the disease process: Asbestos fibers generally do their damage when inhaled, although ingestion also poses risks. The microscopic fibers pierce the pleural lining and harm its mesothelial cells, resulting in the formation of malignant plaques. These fibers may be transported by the lymphatic system to the abdomen, or the infected person may cough, produce fiber-infested sputum, and re-ingest it into the abdomen, leading to the peritoneal form of mesothelioma. The worst asbestos fibers seem to be the long, thin fibers of the amphibole minerals. The serpentine mineral chrysotile possesses a feathery fiber that may do less damage, although it is more easily suspended in the air and possibly more subject to inhalation.

Researchers do not completely understand the mechanisms whereby the fibers transform normal cells into cancerous ones, but it is believed that the fibers’ mechanical action on mesothelial cells, followed by inflammation as macrophages gather during the immune response, sets the stage. Asbestos has also been shown to mediate the entry of foreign deoxyribonucleic acid (DNA) into cells, resulting in mutations that lead to the activation of oncogenes, the deletion of tumor-suppressor genes, increased production of free radicals, inactivation of natural cell death (hence uncontrolled cell growth), and other errors. This process may be followed by interactions between the fibers and chromosomes that result in abnormalities, particularly of chromosome 22.

Incidence: Although mesothelioma is a rare form of cancer, its incidence increased in the last two decades of the twentieth century, ranging from 7 to 40 per 1 million in Western, industrialized nations, with several thousand cases diagnosed each year in the United States. (Lung cancer from smoking, by way of comparison, typically strikes 1,000 in 1 million.) Perhaps because of the occupational risk factors, mesothelioma strikes men more often than women, and because it takes years to develop, it is diagnosed most often in those aged sixty and older. Cases in younger persons or with shorter onsets have, however, been reported, and the difficulties of diagnosis (mesothelioma is often misdiagnosed as adenocarcinoma) may mask a higher incidence. Pleural mesothelioma accounts for about 75 percent of all cases, peritoneal mesothelioma about 20 percent, and pericardial mesothelioma about 5 percent.

Symptoms: Pleural mesothelioma is marked by fatigue, anemia, shortness of breath, wheezing, hoarseness, cough, sputum containing blood, and chest pain resulting from the accumulation of fluid in the pleural space. Peritoneal mesothelioma is accompanied by weight loss, cachexia (wasting), abdominal swelling, and pain due to ascites (fluid buildup in the abdominal cavity); bowel obstruction, abnormal blood clotting, anemia, and fever may also appear. In advanced cases of mesothelioma, symptoms may include blood clots in the veins and consequent thrombophlebitis, severe bleeding in many body organs resulting from disseminated intravascular coagulation, jaundice, low blood sugar level, pleural effusion, blood clots in the arteries of the lungs (pulmonary emboli), and severe ascites. Other types of pain, problems in swallowing, and swelling of the neck or face may accompany metastatic tumors.

Screening and diagnosis: Because the symptoms of mesothelioma are common to many conditions and because the disease takes so long to cause severe symptoms, it often remains undetected until well advanced. Unfortunately, no screening tests exist, although researchers are investigating blood levels of osteopontin, a protein associated with mesothelioma, as one means of early detection.

For those whose symptoms have prompted a visit to the doctor, a history of exposure to asbestos, along with a physical examination, lung-function tests, and an X ray, are the first diagnostic steps. If the X ray reveals pleural thickening, computed tomography (CT) or magnetic resonance imaging (MRI) scans usually follow. If these scans show an abnormal amount of fluid or a tumor, aspiration will follow, via pleural tap or chest drain, paracentesis or ascitic drain, or pericardiocentesis, depending on the area affected. Cytology performed on the fluid will reveal or rule out cancer; the absence of abnormal cells would suggest another disease, such as tuberculosis or congestive heart failure.

Even these tests, however, are not sufficient to confirm anything more than the presence of cancerous cells. To diagnose mesothelioma, a biopsy must be performed: thoroscopy if the area is located in the chest, laparoscopy if in the abdomen. These procedures involve small incisions that allow both examination of the cavity and retrieval of tissue samples. Bronchoscopy, in which the physician examines the lung’s airways by means of a bronchoscope, and mediastinoscopy, a method of examining the lymph nodes, are also used. Open surgery may be required if the samples retrieved are insufficient to confirm the diagnosis.

If pathology confirms the suspicion of mesothelioma, the disease will require staging. The precise TNM (tumor/lymph node/metastasis) system is usually employed:

• Stage I: Mesothelioma is confined to the right or left pleura, perhaps in addition involving the lung, pericardium, and diaphragm.





• Stage II: Mesothelioma extends to the chest wall and esophagus, both sides of the pleura, and perhaps the heart.





• Stage III: Mesothelioma extends through the diaphragm into the abdominal cavity.





• Stage IV: Mesothelioma has spread through the bloodstream to distant organs.

For pleural mesothelioma, the Butchart system is most commonly used:

• Stage I: Malignant melanoma is confined to the right or left pleura, perhaps in addition involving the lung, pericardium, and diaphragm.





• Stage II: Malignant melanoma extends to the chest wall and esophagus, both sides of the pleura, and perhaps the heart.





• Stage III: Malignant melanoma extends through the diaphragm into the abdominal cavity.





• Stage IV: Malignant melanoma has spread through the bloodstream to distant organs.

Treatment and therapy: Treatment options for advanced mesothelioma include surgery, most often pleurectomy and decortication (removal of the chest lining) and less often extrapleural pneumonectomy (removal of the lung, interior chest lining, hemidiaphragm, and pericardium). These are followed by radiation and chemotherapy. Chemotherapy for pleural mesothelioma includes a combination of pemetrexed, cisplatin, and folic acid to mitigate pemetrexed’s side effects. A technique known as “heated intraoperative intraperitoneal chemotherapy,” using a heated chemotherapy agent to perfuse affected abdominal and pelvic areas immediately after surgery, has been developed for peritoneal mesothelioma. Investigations into immunotherapies have seen little success, although interferon alpha has shown some promise.

Prognosis, prevention, and outcomes: Because diagnosis generally occurs late and the disease is aggressive, survival rates are low, tending to average between six and nine months following diagnosis, depending on the type of mesothelioma. In the United States, the death rate from mesothelioma increased from 2,000 to 3,000 per year between 1980 and the late 1990s.

Radiation and chemotherapy are offered as palliative treatments in advanced cases. A thin tube or needle may be installed in the affected region (via paracentesis for the abdomen and thoracentesis for the chest cavity) to relieve fluid buildup and consequent pain.

A diagnosis of mesothelioma is not necessarily a death sentence, however: Paleontologist Stephen Jay Gould, who was diagnosed with peritoneal mesothelioma, lived two decades after his diagnosis and succumbed to a different disease. Fortunately, mesothelioma remains a rare and highly preventable disease if asbestos exposure is identified and eliminated.

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