How is mesothelioma diagnosed?
A diagnosis of mesothelioma is most often obtained with careful assessment of clinical and radiological findings in addition to a confirming tissue biopsy. A review of the patient's medical history, including history of asbestos exposure is taken, followed by a complete physical examination, x-rays of the chest or abdomen, and lung function tests. A CT scan or MRI may also be done at this time. If any of these preliminary tests prove suspicious for mesothelioma; a biopsy is necessary to confirm this diagnosis.
Imaging Techniques and Their Value in Diagnosing and Assessing Mesothelioma
There are several imaging techniques which may prove useful when mesothelioma is suspected due to the presence of pleural effusion combined with a history of occupational or secondary asbestos exposure. While these imaging techniques can be valuable in assessing the possibility of the cancer, definitive diagnosis is still most often established through fluid diagnosis or tissue biopsy.
Some of the most commonly used imaging methods include:
• X-ray
A chest x-ray can reveal pleural effusion (fluid build-up) which is confined to either the right (60%) or left (40%) lung. On occasion, a mass may be seen. Signs of prior non-cancerous asbestos disease, such as pleural plaques or pleural calcification, or scarring due to asbestosis may also be noted.
• Computed Tomography (CT)
CT scans are also able to define pleural effusion, as well as pleural thickening, pleural calcification, thickening of interlobular fissures, or possible chest wall invasion. CT, however, is not able to differentiate between changes associated with benign asbestos disease (pleural disease), or differentiate between adenocarcinoma of the lung wh
ich may have spread to the pleura verses mesothelioma.
• Magnetic Resonance Imaging (MRI)
MRI scans are most often used to determine the extent of tumor prior to aggressive treatment. Because they provide images in multiple planes, they are better able to identify tumors as opposed to normal structures. They are also more accurate than CT scans in assessing enlargement of the mediastinal lymph nodes (those lymph nodes which lie between the two lungs), as well as a clear diaphragmatic surface, both of which play an important role in surgical candidacy.
• Positron Emission Tomography (PET)
PET imaging is now becoming an important part of the diagnosis and evaluation of mesothelioma. While PET scans are more expensive than other types of imaging, and are not always covered under insurance, they are now considered to be the most diagnostic of tumor sites, as well as the most superior in determining the staging of mesothelioma.
• CT/PET
For patients who may be candidates for aggressive multimodality treatment (surgery, chemotherapy and radiation), accurate clinical staging is extremely important. Integrated CT/PET imaging provides a relatively new tool in this respect, and has become the imaging technique of choice for determining surgical eligibility. By combining the benefits of CT and PET (anatomic and metabolic information) into a single scan, this technology can more accurately determine the stage of the cancer, and can help identify the best treatment option for the patient.
A needle biopsy of the mass, or the removal and examination of the fluid surrounding the lung, may be used for diagnosis, however, because these samples are sometimes inadequate as far as determining cell type or because of the unreliability of fluid diagnosis, open pleural biopsy may be recommended. In a pleural biopsy procedure, a surgeon will make a small incision through the chest wall and insert a thin, lighted tube called a thoracoscope into the chest between two ribs. He will then remove a sample of tissue to be reviewed under a microscope by a pathologist. In a peritoneal biopsy, the doctor makes a small incision in the abdomen and inserts a peritoneoscope into the abdominal cavity.
Once mesothelioma is suspected through imaging tests, it is confirmed by pathological examination. This is the end of a process that usually begins with symptoms that send most people to the doctor: a fluid build-up or pleural effusions, shortness of breath, pain in the chest, or pain or swelling in the abdomen. The doctor may order an x-ray or CT scan of the chest or abdomen. If further examination is warranted, the following tests may be done:
- Video-Assisted Thoracoscopic Surgery (VATS)
Over the past decade, the use of video-assisted thoracic surgery (VATS) has become one of the most widely used tools in the diagnosis of mesothelioma. Biopsies of the pleural lining, nodules, masses and pleural fluid can now easily be obtained using this minimally invasive procedure, and other therapies such as pleurodesis (talc) for pleural effusions can be done concurrently.While the patient is under general anesthesia, several small incisions or “ports” are made through the chest wall. The surgeon then inserts a small camera, via a scope, into one incision, and other surgical instruments used to retrieve tissue samples into the other incisions. By looking at a video screen showing the camera images, the surgeon is able to complete whatever procedures are necessary
In many cases, this video-assisted technique is able to replace thoracotomy, which requires a much larger incision to gain access to the chest cavity, and because it is minimally invasive, the patient most often has less post-operative pain and a potentially shorter recovery period.
For pleural mesothelioma the doctor may look inside the chest cavity with a special instrument called a thoracoscope. A cut will be made through the chest wall and the thoracoscope will be put into the chest between two ribs. This test is usually done in a hospital with a local anesthetic or painkiller.
If fluid has collected in your chest, your doctor may drain the fluid out of your body by putting a needle into your chest and use gentle suction to remove the fluid. This is called thoracentesis.
For peritoneal mesothelioma the doctor may also look inside the abdomen with a special tool called a peritoneoscope. The peritoneoscope is put into an opening made in the abdomen. This test is usually done in the hospital under a local anesthetic.
If fluid has collected in your abdomen, your doctor may drain the fluid out of your body by putting a needle into your abdomen and using gentle suction to remove the fluid. This process is called paracentesis.
If abnormal tissue is found, the doctor will need to cut out a small piece and have it looked at under a microscope. This is usually done during the thoracoscopy or peritoneoscopy, but can be done during surgery.
Pathology and The Role of Pathologists in the Diagnostic Process
Pathology, or the scientific study of cells, tissue, or fluid taken from the body is an integral part of a mesothelioma diagnosis. Most hospitals have their own pathology labs staffed by board-certified pathologists and licensed technologists. The importance of pathological diagnosis can not be underestimated, since the course of treatment is dependent upon an accurate diagnosis.
To make a diagnosis, pathologists examine tissue under a microscope, and based on established criteria, make a determination of benign vs. malignant cells. Subsequently, the type of cancer is determined. Although most pathologists have a general expertise of various diseases, a small number acquire training in a subspecialty, such as mesothelioma. These are physicians who have received world-wide recognition as premier experts, and have achieved high acclaim for their research, published articles and abstracts, and teaching.
Knowing the stage is a factor in helping the doctor form a treatment plan. Mesothelioma is considered localized if the cancer is confined to the pleura, or advanced if it has spread beyond the pleura to other parts of the body such as the lungs, chest wall, abdominal cavity, or lymph nodes.
Immunohistochemical Markers for Mesothelioma
A diagnosis of any specific type of cancer often means ruling out other cancers in the process. This is true in the case of mesothelioma, where the most common “differential diagnosis” is that of adenocarcinoma versus mesothelioma.
During the biopsy procedure, the surgeon removes tissue samples to be sent to the laboratory. In the lab, slides are produced and then viewed and analyzed by a pathologist. These tissue specimens arrive at the lab with a request form that details patient information and history along with a description of the site in the body from which the specimen was obtained. Each individual specimen is numbered for each patient.
The pathologist then does a “gross examination” which consists of describing the tissue, and then placing it in a plastic cassette. The cassettes are then placed in a fixative that preserves the tissue permanently. Once the tissue has been fixed, it is processed into a paraffin block that will allow the pathologist to slice off thin microscopic sections that will then be stained to determine the patient’s diagnosis.
Immunohistochemistry is defined as “a method of analyzing and identifying cell types based on the binding of antibodies to specific components of the cell”.
Early on, the “markers” which helped distinguish mesothelioma from adenocarcinoma were “negative markers”; those expressed in adenocarcinomas, but not in mesotheliomas. This made it more difficult to confirm a diagnosis, because pathologists were dealing with the absence of, rather than the presence of certain markers. Some of these markers, which are normally “positive” in an adenocarcinoma diagnosis and “negative” in a mesothelioma diagnosis, are carcinoembryonic antigen (CEA), CD 15 (LeuM1), epithelial glycoprotein (Bg8), tumor glycoprotein (BerEp4) and tumor glycoprotein (MOC-31).
In more recent years, “positive markers” expressed by mesotheliomas have come to the forefront. Some of the markers which are normally “positive” in mesotheliomas and “negative” in adenocarcincomas are calretinin, cytokeratin 5, HBME-1, mesothelin, N-cadherin, thrombomodulin, vimentin and Wilm’s tumor gene product (WT-1).
It is important to remember that while the above markers are commonly used to help diagnose the epithelial sub-type of mesothelioma, that they may also be expressed in other types of cancer, and may not necessarily apply to the bi-phasic or sarcomatoid sub-types of mesothelioma. Your doctor can always contact a more specialized lab if he/she feels your diagnosis is in any way inconclusive.
