Overall prognosis is poor with a mean survival of 8-14 months. Staging is not routinely performed because of the overwhelming lack of surgical exploration. Rather, disease severity is determined to guide treatment. Therefore, information acquired at the time of diagnosis will provide some insight into the prognosis. Sarcomatous subtype histology (accounting for 10%) or uncertain histology is correlated with a poorer prognosis. Poor performance status, male gender and age over 75 consistently carry poor prognosis. Symptoms of chest pain and dyspnea as well as pleural involvement do not bode well for the patient. Certain lab tests will also indicate shorter survival, such as low hemoglobin, platelet count greater than 400 000, WBC count over 8300, or LDH over 500.
The use of radiotherapy is quite limited. While it may offer a palliative role, tumor volume and tissue toxicity restrict its usefulness. Surgical procedures, such as those that debulk the tumor mass, are limited by the ability of the patient to undergo radical resection. Like radiation, surgery may also offer palliation; there is little evidence to suggest that either of these modalities have any other significant impact on the course of the disease. The impact of single-agent chemotherapy is varied. Approximate response rates range anywhere from 0-35% with cisplatin and methotrexate as the most effective drugs. Combination chemotherapy using traditionally available medications does not seem to have any more positive effect than single-agent and is therefore not widely used. However, emerging trials indicate there may be some benefit to therapy with newer agents when combined with platinums.
Definitive diagnosis of pleural mesothelioma remains difficult. Over half of all patients requiring analysis of pleural effusion will have a malignancy. CT will provide additional benefit in determining the extent of involvement and is usually used to guide biopsy. Recently, PET has emerged as superior to CT or MRI when evaluating pleural thickening as found on CT with a rate of accuracy at 94%. Thoracocentesis is widely performed to obtain cytology but does not often lend insight into the diagnosis, carrying a sensitivity of only 30% in pleural mesothelioma. Work-up is further complicated as tumor invasion occurs in 40% of study sites. Thoracoscopy is considered the gold standard for the evaluation of exudative pleural effusions in those with negative cytology. In mesothelioma, open pleural biopsy is often required but distinction from other pathology is difficult as pleural fluid tends to be both hemorrhagic and exudative.
Although relatively rare, the incidence of mesothelioma has increased over the last 20 years with roughly 2,000 new cases reported in the U.S. each year. The disease is more common in men with a male-to-female ratio of 3:1. Occupational exposure to asbestos is reported in 3-4 out of every 5 cases. Those who work with asbestos carry an overall 8% lifetime risk of developing malignant pleural mesothelioma. Increase in both time and intensity of exposure increases the risk for all asbestos-related disease. Even those indirectly exposed, such as family members of asbestos workers, have an increased risk of mesothelioma. Cigarette smoking does not increase the incidence of mesothelioma. However, it should be noted that a combined history of asbestos exposure and smoking increases the risk of bronchogenic cancer. Additionally, not all cases of mesothelioma have an identified exposure to asbestos and not all who are exposed to asbestos will develop asbestos-related disease.
Pleural mesothelioma typically presents insidiously with symptoms of pleural effusion, including dyspnea and chest pain. Weight loss is common. Physical exam will yield diminished breath sounds and dullness to percussion. A history of asbestos exposure occurs in 60-80% of those with malignant mesothelioma with symptoms presenting 20-50 years after exposure. The average age at symptom onset is 60 years old. Occupational exposure occurs with the mining and manufacturing of asbestos and its products or with direct handling of these products (insulation, textiles, paint, brake linings, gaskets, etc.). Symptoms of peritoneal mesothelioma are similar to those of other abdominal cancers and include abdominal pain, ascites, or bowel obstruction. Additionally, fever and anemia are seen. Pulmonary asbestosis is seen in over half of all cases. Occasionally, peritoneal mesothelioma presents with lymphadenopathy or, in women, a pelvic mass.
Regardless of the location, malignant mesotheliomas occur in three forms. The epithelioid type is the most common, accounting for 50-70% of all mesotheliomas. Between 20-35% of mesotheliomas are sarcomatoid, or fibrous. These cells are typically oval shaped, but more irregular, and with the nucleus not as clearly visible under an electron microscope as the nuclei of the epithelioid mesothelioma cancer cells. Because the oval irregular shape is a common form of a cancer cell type, sarcomatoid mesothelioma can be confused with sarcomatoid carcinoma and with sarcoma. The remaining 7-20% of tumors are classified as mixed/biphasic. Epithelioid mesothelioma has the best outlook for survival. Biphasic mesothelioma cancer typically produces a combination of epithelioid and sarcomatoid cancer cells as opposed to a mixture, meaning that the two subtypes occur in different parts of the tumor.
Pleural mesothelioma can cause these symptoms:
• Chest wall pain, may be in the side or lower back
• Pleural effusion
• Dyspnea
• Wheezing, and/or persistent cough
• Husky voice, hoarseness
• Difficulty swallowing
• Fever
• In severe cases, the person may have many tumor masses. The individual may develop a pneumothorax, or collapse of the lung.
• Pleural tumors are usually found on only one side of the lung.
Peritoneal mesothelioma can cause these symptoms:
• Cachexia, (physical wasting with loss of weight and muscle mass caused by disease)
• Abdominal pain and swelling due to ascites (may be severe)
• Abdominal mass
• Bowel dysfunction
• Thrombophlebitis
• Disseminated intravascular coagulation
• Jaundice
• Hypoglycemia
• Pleural effusion
• Pulmonary emboli
A mesothelioma does not usually spread to the bone, brain, or adrenal glands.
Insulating materials before the mid-1970’s commonly contained asbestos. In addition to household attic insulation, these included: pipe and boiler insulation, fireproofing, insulating cements, plaster, and joint materials, firebrick and gunnite, roof floor and ceiling tiles, transite siding, brakes and clutches.
“The following tradesmen could have worked around asbestos:
• Insulators (also known as asbestos workers) who actually installed insulation
• Boilermakers who constructed boilers which were often several stories high and filled with insulation
• Plumbers, pipefitters, and steamfitters who fitted and welded pipes together and often worked in small unventilated compartments in ships where large quantities of insulation were used
• Plasterers who worked with fireproofing spray on steel beams
• Shipyard workers and Navy personnel
• Electricians, mechanics
• Bricklayers; millwrights; carpenters; and other building trades workers
• Steel workers; refinery and other industrial workers;
• Maintenance workers; laborers; many others. “
Being a cancer, mesothelioma, or unrestrained growth and spread of the mesothelium, is, like all cancers, caused by injury to DNA that results in mutations in genes that direct cell division. The wildly growing and abnormal mesothelium can spread into adjacent tissues, or implant into remote tissues by metastasis via the circulatory or lymphatic systems. Most mesothelioma cases develop in the pleura or the perioneum (one-fifth to one-third of all cases.) The carcinogens most closely associated with mesothelioma are asbestos and smoking. Over fifty percent of people diagnosed with mesothelioma have had a history of asbestos exposure, sometimes for as little as three months. The latency period between asbestos exposure and development of mesothelioma can be as long as fifty years. Exposure to Eronite, a mineral that has a long, thin rod-like amphibole structure, has a high mortality rate due to mesothelioma in Anatolia, Turkey.
Mesothelioma is a cancer of the mesothelium. The mesothelium is composed of flat, squamous epithelial cells forming a double-layered membrane lining several body cavities. This mesothelium derives from the embryonic mesoderm cell layer which lines the body cavity (coelum) of the embryo. The visceral layer of the mesothelium closely surrounds the organ; the parietal mesothelium forms a protective sac around the organ. The mesothelium secretes a cushioning, lubricating fluid between these two layers so that the organ(s) can slip freely along contiguous viscera. The mesothelium has several different names deriving from the part of the body that it protects: around the heart it is called the pericardium; around the lungs, the pleura; around the abdominal cavity, the peritoneum; around the internal male reproductive organs, the tunica vaginalis testi; around the internal female reproductive organs, the tunica serosa uteri.