An international panel of pathologists has released a consensus statement regarding guidelines for the pathological diagnosis of diffuse malignant mesothelioma. Among the key recommendations: antibody tests (immunohistochemical studies) are crucial to distinguishing mesothelioma from other types of cancers, and a patient’s history of asbestos exposure should not play a role in making the pathologic diagnosis.
The expert panel included 16 pathologists from the International Mesothelioma Interest Group. Their goal was to provide guidelines to pathologists who do not have extensive experience in diagnosing mesothelioma.
“What started the whole project was that our oncologists at the University of Chicago felt there were pathologists who saw maybe one case of mesothelioma every two or three years,” explains Aliya Husain, MD, Professor of Pathology at the University of Chicago. “They did not see mesothelioma often enough to stay up-to-date with the extensive literature from multiple sources. There are a lot of antibodies available, and unless you use them often enough, you may not be aware of their sensitivity and specificity, and [you may have] problems with staining patterns and interpretation.”
Antibody markers are used in immunohistochemical (IHC) stains, and are among the most sensitive lab tests for distinguishing mesothelioma from other types of cancers. When a lab receives a tissue sample taken from a patient, pathologists use a panel of antibodies to compare the staining pattern of mesothelioma, which is different from that of other tumors that may resemble mesothelioma (such as adenocarcinoma).
The guidelines assess the usefulness of various antibodies. They do not recommend any specific number or type of antibodies to use in this test, because no one panel exists that is ideal for diagnosing all mesotheliomas. However, they do stress that each lab should develop its own standardized set of antibodies from the panels provided. “Depending on the types of tumors being tested, the pathologist needs to have a panel that works in that setting,” says Dr. Husain. The clinical features, location and characteristics of the tumor, as well as the lab’s experience, should determine which panel to use. Labs need to choose antibodies that are at least 80% sensitive, and all tests should have controls against which to compare the results, according to the guidelines.
Although mesothelioma has been directly linked to asbestos exposure, the authors of the guidelines say pathologists shouldn’t consider a patient’s past asbestos exposure when diagnosing the disease. “You cannot say that just because a patient has been exposed to asbestos, the tissue that you have on biopsy is mesothelioma,” Dr. Husain says. “They can get other cancers as well.”
Today, a panel of antibodies (IHC stains) is the most widely used method for diagnosing the disease on biopsy. “More than 95 percent of the time you can make a definite diagnosis. In the remainder, the amount of tissue may be insufficient or not representative of the tumor, or the tumor is so undifferentiated that it cannot be classified,” according to Dr. Husain. “Additionally, there are always some cases in which differentiating benign reactive processes from malignancy [cancer] can be difficult.”
Accumulating data shows that there are characteristic molecular alterations in malignant mesothelioma. In the future, the use of genetic tests could make diagnosing mesothelioma easier. “Molecular testing would be very helpful if you have a limited amount of tissue, and in difficult cases in which you’re not sure whether tissue is benign [noncancerous] or malignant [cancerous],” says Dr. Husain. Currently these tests are very expensive and available only in research laboratories because they still need to be validated in human studies, but Dr. Husain says they should become more widely available in the years to come.
Husain AN, et al. Guidelines for pathologic diagnosis of malignant mesothelioma: A consensus statement from the International Mesothelioma Interest Group. Archives of Pathology and Laboratory Medicine. Vol. 133, No. 8, pp. 1317-1331.