- The most common presenting symptoms of mesothelioma are shortness of breath and non-pleuritic chest pain.
- Weight loss, fatigue, fever, and sweats are other symptoms of mesothelioma.
- The lung exam may reveal dullness to percussion and diminished breath sounds.
- Another physical exam finding may be finger clubbing which is also found in asbestosis.
- Radiographic studies may aid in the diagnosis of mesothelioma.
- Chest x-rays may reveal nodular, irregular, unilateral pleural thickening and unilateral pleural effusion.
- CT scans are helpful in determining the extent of pleural involvement.
- Abdominal CT may show sheet-like masses involving the omentum and mesentery.
- Pleural fluid is usually exudative and may be hemorrhagic, but this is not diagnostic.
- Open pleural biopsy is necessary for histologic diagnosis.
- Histological types of mesothelioma are epithelial, sarcomatous, or mixed.
- Special stains and electron microscopy may be needed to confirm the histologic diagnosis.
- Diagnosis of mesothelioma is confirmed by thoracoscopy or pleuroscopy.
The typical patient with mesothelioma will be a male in his 50s to 70s with a history of working in a profession where there is a high risk of exposure to asbestos.
Professions with a high risk of asbestos exposure include construction workers, railroad workers, naval mechanics, bakers, automobile mechanics and explosive workers.
Women also do develop mesothelioma, but it is more common in men at a ratio of 3:1.
Women who develop mesothelioma also have a history of working in high risk professions for asbestos exposure or may have been exposed to asbestos secondary to inhaling fibers off of the clothing of a person who has been exposed to asbestos.
The period between exposure to asbestos and developing symptoms of malignant mesothelioma can range from 20-40 years.
Survival rate after the onset of symptoms can be as little as five months in extensive disease and sixteen months in localized disease.
Majority of patients die within a year after diagnosis.
Stage One
The tumor is confined within the capsule of the pleura.
Stage Two
The tumor is confined within the capsule of the pleura and there are positive intrathoracic lymph nodes
Stage Three
There is local extension of the disease into the chest wall, heart, and peritoneum with or without extrathoracic lymph node involvement
Stage Four
Distant metastatic disease
Mesothelioma is staged using the TNM classification system for classifying malignant tumors.
- The T refers to the size and local spread of the primary tumor
- Size of the tumor can be designated by the number 1-4
- The N describes spreading of the tumor into lymph nodes
- Spread of the tumor to lymph nodes can be designated by the numbers 0-3
- N0- there is no spread to lymphatic nodes
- N1-there is spread of the tumor to nearest lymph nodes
- N3- there is spread of the tumor cells to distant lymph nodes
- The M describes distance metastasis
- Metastasis is designated by the numbers 0-1
- M0- no metastasis
- M1-metastasis to distant tissues
The cells that normally line the pleura and peritoneum are called mesothelial cells. Primary tumors that arise from mesothelial cells are mesotheliomas. Eighty percent of mesotheliomas arise from the pleura; the other twenty percent of mesotheliomas arise from the peritoneum.
Seventy-five to ninety percent of mesotheliomas are malignant. The majority of mesotheliomas are described as malignant pleural mesotheliomas.
The majority of mesotheliomas are caused by asbestos. Asbestos are naturally occurring, heat-resistant fibrous silicates. The fibers of asbestos can be long and thin and maybe curved or straight. The straight fibers of asbestos are called amphiboles. There are five different types of amphiboles, however the type associated with mesothelioma is crocidolite.
Another cause of mesothelioma is thorium dioxide which is used in therapeutic radiation. Mesotheliomas are also thought to be caused by zeolite (a silicate found in soil).
Although the onset of the disease is insidious, once established, malignant mesothelioma progresses rapidly by local extension to the pericardium, mediastinum, and contralateral pleura. Pain and dyspnea become progressive. Extension to other thoracic structures creates superior vena cava syndrome, hoarseness, and dysphagia. Abdominal extension is common and involves the abdominal lymph nodes and organs. Mesothelioma is associated with the development of paraneoplastic disorders, which include thrombocytosis, hemolytic anemia, Disseminated Intravascular Coagulation, and migratory thromboplebitis. Tumor recurrence rate after surgery is as high as 50%.
Death results from respiratory failure and local extension to other organs. Untreated mesothelioma is fatal in 4-8 months. Patients who receive multimodality care may survive 16-19 months. The five-year survival rate is less than 5%.
Mesothelioma may be treated with surgery, chemotherapy, radiotherapy, or a combination of modalities. Surgery is an option for patients with disease confined to the pleural space, but resection is relied upon even in more widespread cases because radiation and chemotherapy are ineffective as primary treatments. With surgery alone recurrence rates are very high.
Pleurectomy is a limited surgical procedure that involves dissection of the tumor from the pleura and has a mortality rate of 2%. A more extensive approach is extrapleural pneumonectomy, which involves en bloc resection of the pleura. Although this second approach has a higher mortality rate it provides better local control of the disease.
Active chemotherapeutic agents include anthracycline, platinum, and alkylating agents, which have effective rates of 10-20%. Cisplatin is the drug used most often in phase III trials.
Radiation therapy does not affect survival rate but is used as a palliative measure in combination with other treatments.
Thoroscopy and pleuroscopy are utilized to confirm the diagnosis and obtain samples for pathological analysis and tumor staging. Special stains and electron microscopy may be needed for the diagnosis. Fluoroscopically guided biopsy is diagnostic in 98% of cases. Pleural fluid is often exudative and hemorrhagic although it is not usually diagnostic except in occasional cases where malignant mesothelial cells are found.
Imaging studies included chest radiographs, CT, MRI, and PET scans. Chest films may show obliteration of the involved diaphragm and a ground glass appearance, pleural thickening, pleural encasement, and decreased size of the involved hemithorax.
TMN classification of the International Mesothelioma Interest Group stages mesothelioma as follows:
Stage I – Completely contained without adenopathy
Stage II – Intrapleural adenopathy
Stage III – Local extension into the chest wall
Stage IV – Distant metastases
Pleural mesothelioma has an insidious onset of symptoms including shortness of breath and unilateral, non-pleuritic chest pain, which occurs in 60-90% of patients. Other symptoms such as cough, fever, weight loss, night sweats and generalized malaise are less common. These are non-specific symptoms that may occur with other disorders including lung and other cancers. There is no pathognomonic sign or symptom for mesothelioma. Patients may also be asymptomatic. The mean age at presentation of patients with mesothelioma is 60 years of age.
Peritoneal mesothelioma may present with abdominal distention and abdominal pain as a result of fluid accumulation. Fever, weight loss, constipation, anemia, clotting disorders, or an abdominal mass are other signs of peritoneal mesothelioma.
Upon physical exam the clinician may find unilateral diminished breath sounds, dullness to percussion of the thorax or abdomen. A late finding is digital clubbing, a finding associated with many cardio-pulmonary and neoplastic disorders.
1. Cancers from the lung, breast, ovary, and GI tract may all metastasize to mesothelium.
2. Benign Fibrous Pleural Mesothelioma- these are well localized tumors which appear as nodules on imaging. Patients are often asymptomatic and these are incidental findings on imaging. On occasion individuals may present with cough, chest pain or shortness of breath.. There is no apparent relationship to asbestos exposure and development of this tumor.
3. Granulomatous Lesions- may occur after surgery from cautery or a foreign body reaction such as to Talc or other irritating agent
4. Pulmonary and Peritoneal fibrosis