Hi Everyone. Today I wanted to teach you about mesothelioma. So, first of all, we need to see the learning objects. Lets checkout this first.
- what is mesothelioma?
- What is its incidence and why is its incidence changing?
- How is asbestos involved?
- And how would a patient with mesothelioma present?
- What might you see on physical exam with a patient with mesothelioma?
- What other diseases might present like this?
- How do you diagnose mesothelioma?
- And how might you treat mesothelioma?
The introduction, we’ll talk about, then we’ll move on to epidemiology.
We’ll talk about asbestos involvement. We will then move to clinical features. We’ll talk about the objective findings.
We’ll then go on to talk about a differential diagnosis for mesothelioma, and then you’ll need to see the diagnostic workup involved.
And finally, we’ll talk about the treatment modalities involved with mesothelioma.
I believe in order to get started with the introduction to mesothelioma, I will introduce you to a case. I’ll tell you about a 70-year-old man who presents shortness of breath, chest pain, and weight loss.
Lung exam reveals dullness to percussion at the site of his pain, with diminished breath sounds in that area of his hemithorax.
A chest CT shows moderate pleural effusions at the site, with visceral pleural thickening.
Actual lung parenchyma is minimally involved, and cytologic examination of that pleural effusion reveals malignant cells.
As this slide tells you, mesothelioma is an aggressive and deadly form of cancer. Mesothelioma occurs in a thin layer of tissue called the mesothelium that covers most of your internal organs.
It is most commonly associated with high exposure to asbestos and represents less than 1% of all cancers.
Malignant mesothelioma is cancer of the pleura and, less commonly, the peritoneum, associated with exposure to asbestos.
The incidence in the United States is estimated at 3,000 cases per year.
More than 90% of cases are pleural, less than 10% peritoneal. Men have a five to six-fold higher incidence than women.
Worldwide incidence is increasing, although incidence rates have leveled off in the United States and Scandinavia, where restrictions on asbestos exposure occurred earlier than in Western Europe and Australia.
Approximately 90% of patients with mesothelioma have a history of exposure to asbestos.
There is a dose-response relationship with asbestos exposure and no safe threshold of exposure has been identified.
The mean latency after initial asbestos exposure and clinically detectable mesothelioma is about 37 years, a range of 40 to 75.
Past asbestos exposure is non-occupational settings such as homes, or from environmental exposures near mines and factories.
These may explain the minority of cases which occupational exposure is not identified.
In addition, asbestos exposure to erionite, a long fiber used for home building in Turkey, increases the risk for mesothelioma.
Smoking is not a risk factor for mesothelioma.
Asbestos exposure, in association with smoking, increases the risk for lung cancer and pleural and peritoneal mesothelioma.
Most cases of mesothelioma– about 50% to 80%– occur in patients who were exposed to asbestos.
Such individuals have a lifetime risk of about 2% to 10% for this otherwise uncommon malignancy.
The latency period is frequently mentioned, and likely to be tested. This would be 30 to 40 years. The USA has a declining incidence of this disease thanks to better regulations, but it still leads in its total number of cases.
Many other areas worldwide continue to see their incidence rise. Asbestos-related cancers include malignant mesothelioma and lung cancer.
Cigarette smoking interacts with asbestos exposure in raising the risk for lung cancer, but not for mesothelioma.
This interaction is often described as a synergistic effect. That is, the increased risk for lung cancer in asbestos-exposed workers who smoke is greater than would be predicted if these two exposures were independent of each other.
The latency period from initial asbestos exposure to the diagnosis of lung cancer is 10 years or longer, with the peak incidence occurring approximately 25 years after exposure.
The latency period from initial asbestos exposure to the diagnosis of mesothelioma is even longer, as mentioned previously.
I present to you another case. I have a 68-year-old retired construction worker, who has complained of right-sided chest pain and shortness of breath with a dry cough.
There is marked weight loss and anorexia. A chest x-ray shows right pleural effusion with pleural thickening.
The right-sided effusion is bloody, and the white blood cell count within that effusion is 1,200, with 50% polys, 5% lymphocytes, and 80% reactive mesothelial cells.
The red blood cells in this fluid are 130,000, with a protein of 4.2 grams per liter, and a serum protein of 4.6.
There’s an LDH in this fluid of 560, with a serum LDH of 226,and a pH of 6.90.nThis fluid is thereby exudated, according to Light’s criteria with a pleural fluid protein divided by a serum protein of greater than 0.5.
Also, the pH of less 7.2 indicates an exudative effusion. This 68-year-old retired construction worker presents with characteristic features of mesothelioma.
Mesothelial cells are primary tumors that arise from mesothelial cells that line the pleural cavity.
They produce a hemorrhagic effusion. A bloody effusion, and the absence of acute trauma, always suggests malignancy.
Thoracoscopy with pleural biopsy is usually necessary to make a definitive diagnosis.
What might you see on the exam?
Pleural effusions and ascites are the underlying cause of most of the exam findings. The exam will show dullness to percussion at these sites.
Lung exam will likely be described as dullness to percussion with decreased breath sounds, best defining a pleural effusion.
Chest x-rays will confirm the effusions, and may even hint at the pleural thickening.
Now, the differential diagnosis of mesothelioma includes inflammatory reactions such as chronic organized empyema, which mimics the pleural thickening and large pleural effusions are seen with mesothelioma.
Metastatic involvement of the pleura may also look like mesothelioma, with possible primary sources including– but is not limited to– the lung, breast, stomach, kidney, ovary, thymus, and prostate.
Sarcoma and malignant fibrous histiocytoma may also look like mesothelioma.
Malignant pleural mesothelioma typically presents with chest pain, usually associated with pleural effusion.
Cough, dyspnea, weight loss, fever, and malaise are common.
CT scanning is the primary imaging modality used for diagnosis and staging.
Findings include irregular nodular pleural thickening or masses with effusion. Invasion occurs locally along the pleural cavity.
As the disease progresses, and in advanced disease, the lung parenchyma and mediastinal and hilar lymph nodes may be involved, along with pericardial thickening or effusion, abdominal extension, and chest wall invasion.
Surgical lung biopsy is needed to confirm the diagnosis with the VATS.
The biopsy specimen is positive in more than 80% of cases, and with open thoracotomy in more than 90%.
Mesothelioma may be differentiated from metastatic adenocarcinoma by immunohistochemical staining.
This picture here is a psammoma body and this is frequently tested as a common finding with mesothelioma.
Mesothelioma is progressive, with a tumor growing locally to encase the lung and surrounding organs.
Survival is approximately 10% at 24 months, even with palliative therapy.
Improved survival is associated with epithelial cell type, pleural rather than peritoneal location, and age under 65 years at diagnosis.
Multi-modal therapy such as extrapleural pneumonectomy, or pleurectomy, and decortication, followed by chemotherapy and radiation, are under investigation.
Combined modality therapy, though not curative, may prolong survival. Pemetrexed, a new, multi-targeted antifolate appears to slow the rate of mesothelioma progression, either alone or combined with a platinum agent or gemcitabine.
Let’s make sure all of these are answered.
Number one, mesothelioma–or more precisely, malignant mesothelioma– is a rare form of cancer that develops from transform cells originating in the mesothelium, the protective lining that covers many of the internal organs of the body. It is usually caused by exposure to asbestos.
Number two, the incidence in the United States is estimated at 3,000 cases per year.
More than 90% of cases are pleural, less than 10%, peritoneal. Men have a five to six-fold higher incidence than women. Worldwide incidence is increasing, although incidence rates have leveled off in the United States and Scandinavia, where restrictions on asbestos exposure occurred earlier than in other Western European and Australian countries.
Number three, approximately 90% of patients with mesothelioma have a history of asbestos exposure.
There is a dose-response relationship with asbestos exposure, and no safe threshold of exposure has been identified.
The mean latency after initial asbestos exposure and clinically detectable mesothelioma is 37 years.
Cigarette smoking interacts with asbestos exposure in raising the risk of lung cancer, but not for mesothelioma.
This interaction is often described as synergistic– that is, the increased risk for lung cancer in asbestos-exposed workers who smoke is greater than would be predicted if these two exposures were independent of each other.
Number four, I want to tell you about the case that we talked about, which is an older male complaining of chest pain and shortness of breath with a dry cough.
He may or may not tell you about asbestos exposure in his past. Cough, dyspnea, weight loss, fever, and malaise are common with this disease.
On exam– the next question– you may look for evidence of pleural effusion and ascites.
In the end stages, you may also even start to see cachexia and muscle wasting.
The exam will show dullness to percussion at the effusion and ascitic sites.
Lung exam will likely be described as dullness to percussion with decreased breath sounds, thus defining the pleural effusion, and chest x-rays will confirm that effusion, and even hint at some pleural thickening.
Number six, what other diseases look like this? Any other lung cancer or chronic inflammatory reaction can cause thickening of the pleura, that may look like mesothelioma.
Cancers metastasizing to the pleura and sarcoma also may look like mesothelioma.
Number seven, how do you diagnose it?
CT scanning is the primary imaging modality used to diagnose and stage. Findings include irregular nodular pleural thickening or masses with effusion.
Invasion occurs locally along the pleural cavity. As the disease progresses and in advanced disease, the lung parenchyma and mediastinal and hilar lymph nodes may be involved, along with pericardial thickening or effusion.
Abdominal extension and chest wall invasion are also common. And finally, how do you treat it? Treatment options for the management of malignant mesothelioma include surgery, chemotherapy, radiation, and multi-modality treatments.
Surgery in patients with the disease confined to the pleural space is the most reasonable.