Diagnosis

How doctors diagnose mesothelioma

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Mesothelioma is a serious cancer that, once it reaches the later stages, grows quickly and aggressively.  Although a new mesothelioma blood test has recently been developed that may help in the earlier diagnosis of the disease, mesothelioma is not usually diagnosed until the disease has already progressed to the later stages.  This is due to the disease’s long latency period.  Usually, the first symptoms of mesothelioma only begin to appear decades after the initial exposure to asbestos.  Another reason that mesothelioma is not diagnosed earlier is that the early warning signs are so non–specific, they often resemble the symptoms of other more common conditions, such as, for example, pneumonia or influenza.  Researchers report that mesothelioma patients are usually diagnosed within three to six months of the time they first see a physician with complaints about difficulty breathing or chest and abdominal pain.

To reach a diagnosis of malignant mesothelioma, a physician will first obtain a patient history and physical examination.  Next, a series of imaging and diagnostic tests will be conducted.  If the tests suggest that mesothelioma is present, cytology and biopsy procedures may be performed.  Following those procedures, cytology and biopsy testing are necessary to confirm the diagnosis.  After all of these tests have been completed, doctors are able to determine the staging and prognosis for the disease.

Patient History and Physical Examination

The first step in determining whether a patient actually has mesothelioma is a visit to the doctor.  The appointment with the doctor will be more productive and less stressful if time is spent preparing to meet the patient’s mesothelioma doctors. 

For the physician, it will be necessary to begin with the patient’s history.  The doctor will focus in part on the patient’s medical history and physical symptoms.  The patient’s work history — especially any exposure to asbestos — will also be crucial to the physician’s investigation.  Since exposure to asbestos for even a short time can cause mesothelioma, the patient should be forthcoming about any and all possible exposure to asbestos.  This includes exposures that happened decades ago.  It also includes exposure to the clothing of a family member who worked with asbestos.  And it includes exposure from a facility near the patient’s home, which facility mined, processed or manufactured asbestos–containing minerals or products. 

The doctor will also perform a physical exam to look for signs of mesothelioma or other health problems.  A patient with pleural mesothelioma (mesothelioma of the chest) often consults a doctor when experiencing fluid in the chest cavity, called a pleural effusion. Patients with fluid in the abdominal cavity (ascites) may be suffering from peritoneal mesothelioma, while patients with pericardial mesothelioma (mesothelioma of the lining of the heart), often collect fluid there.  The physical examination will check for such customary symptoms and will frequently include a lung function test.  This test allows the doctor to diagnose a number of lung diseases and to gauge the severity of any lung problem.

Imaging and Diagnostic Tests

The physician’s next step in reaching a diagnosis of mesothelioma is to conduct one or several tests, usually involving images of some sort.  These tests can help the doctor to confirm whether cancer is involved, and if so, its location, size and type.  The images will also show whether the cancer, if present, has metastasized, or spread, to other parts of the body.  Because the symptoms of mesothelioma are similar to those of other diseases, advanced imaging technology can be very helpful in distinguishing mesothelioma and reaching a proper diagnosis.  Doctors frequently rely upon the following diagnostic tools during this stage of the investigation:

  • Chest X–ray:  Virtually all diagnoses of mesothelioma will involve a chest X–ray, though more refined images may also be required.
  • CT Scan:  This procedure combines X–ray generated pictures with computer technology to create detailed cross–sectional views of the body’s interior.
  • PET Scan:  After the patient receives a glucose (sugar) solution in an intravenous injection, a scanner is able to highlight clusters of cancer cells, which use sugars more rapidly than normal cells, and are thus easily distinguished in images.
  • MRI Scan:  A strong magnetic field and radio waves work together to create detailed three–dimensional color images of the body’s tissue, organs and blood vessels.
  • Combination Scans:  Imaging devices that combine PET and CT scanners allow nearly simultaneous images, increasing accuracy and the possibility for comparison.
  • Echocardiogram:  Sound waves are used to show the location and extent of any cancer near the heart.

X–rays

An X–ray uses electromagnetic radiation to make pictures of a patient’s bones and internal organs.  The X–ray is one of the oldest types of medical imaging.  The procedure is fast and painless. 
The X–ray of a patient with mesothelioma often shows irregular thickening of the pleura (the thin covering that protects the lungs).  In the case of pleural mesothelioma, the X–ray may also reveal an accumulation of fluid in the lungs (called a pleural effusion).  An accumulation of fluid seen in the abdomen (ascites) may indicate peritoneal mesothelioma. 

CT Scans

Description of the procedure

A CT, or CAT scan — short for computerized axial tomography — is a type of X–ray that makes more detailed images of the internal organs than can be produced by traditional X–rays.  Ordinary X–rays employ a stationary machine to focus radiation beams on a specific area of the body to make two–dimensional images.  CT scans, in contrast, are made with a specialized X–ray device that rotates 360 degrees around the patient all the while directing a precise X–ray beam through the body and creating a large number of images as the patient is moved up or down in the scanner.  The process allows a radiologist to create a series of cross–sectional images of the inside of the body that can be transformed into three–dimensional representations of the body’s internal organs. 

A CT scan is useful in identifying the location and size of any mesothelioma, and will also show if the disease has spread.  It will also reveal the presence of pleural thickening or pleural effusions.  In addition, it may help locate disease outside the pleura, within the chest wall or lymph nodes. 

For most CT scans of the chest, the patient lies on the machine couch while the scanner rotates around the body.  The procedure generally lasts around 20 minutes.  A CT scan is not painful, but it does require the patient to lie perfectly still the entire time, which may become uncomfortable.  The patient is sometimes injected with dye to highlight structures near the suspected cancer.  The IV (intravenous) tube through which the dye is injected may cause redness and a warm feeling in some people.  In those who are allergic, the dye could cause hives or rarely, breathing difficulty or low blood pressure.  The patient should inform the doctor if there is a history of allergies to the contrast material used for x–rays.

When to expect test results

A radiologist who specializes in CT scans interprets the images, and usually will deliver a written report to the patient’s doctor within a few days of the procedure. 

How a CT scan is different

In general, a traditional X–ray works well for highlighting dense structures like bone, and the CT scan is better for viewing soft tissues like the chest or abdomen.  While a traditional X–ray of the abdomen would reveal bones and the outline of some internal organs, for example, a CT scan would show a more precise view of the bones, all the organs, and the blood vessels.

CT scans can be used when an MRI cannot for the patient who has a pacemaker or an internal cardioverter defibrillator in place to help steady the heartbeat.  If the patient is pregnant, however, or thinks she might be, a doctor may recommend postponing the scan or using an alternative procedure, such as an ultrasound or MRI, that doesn’t involve radiation.

PET Scans

Description of the procedure

The term “PET scan” refers to positron emission tomography, a very useful tool for helping physicians to see how the body’s organs and tissues are functioning.  A PET scan allows doctors to create an image of the body so detailed that even the smallest tumor can be seen.  A radioactive tracer isotope, in combination with a form of glucose, is injected into the patient’s blood stream.  After a short time, the “radiotracer” is absorbed into the tissues being studied, and the scanners are able to locate gamma radiation produced by the tracer isotope.  A computer is then used to convert the information into very accurate three–dimensional pictures.
Recent studies suggest that PET scans are extremely helpful in reaching a diagnosis of mesothelioma and determining the stage of the disease.  A study conducted at the University of Pennsylvania Medical Center reported that PET scans were able to identify the presence of mesothelioma in 24 of 24 patients with the disease and to identify 4 of 4 patients who did not have the disease.  In addition, the technology was able to identify tumors in 9 patients’ lymph nodes, although the lymph nodes appeared in CT scans to be normal.  In a separate study at Brigham and Women’s Hospital and Harvard Medical School in Boston, PET scans were able accurately to demonstrate the presence of mesothelioma in 11 patients who had the disease and to confirm the absence of mesothelioma in four patients who had no disease.  In both studies, PET scans compared favorably with laboratory analysis of biopsy materials for purposes of diagnosing the presence of mesothelioma. 

When to expect test results

A radiologist with specialized experience in PET scans interprets the images, usually will deliver a written report to the patient’s doctor within 2 to 3 days after the procedure.

How a PET scan is different

A PET scan is different from a CT scan because it shows metabolic changes in an organ or tissue at the cellular level.  Because disease processes often start with functional changes at the cellular level, a PET scan is able to detect such changes earlier than a CT scan, which cannot detect disease until it causes observable changes in the structure of organs or tissues.  As with a CT scan, a PET scan also involves radiation, making it essential that a patient notify her physician if she is pregnant or thinks she may be.

MRI Scans

Description of the procedure

Magnetic resonance imaging (MRI) scans employ magnetic fields, radio waves, and a computer to make quite clear images of selected areas of the body.  Hydrogen atoms in a patient’s body respond to the magnetic signals by emitting a very slight radio wave, which is then analyzed by a computer.  The images generated are superior to those made by traditional X–ray, and show a greater contrast between tumor and normal tissues.

During the MRI, the patient lies still on a table, which is usually slid inside a large tube that is open on both ends.  The procedure is painless, but the patient is required to lie still for up to an hour, depending on the tests performed.  In addition, the MRI is quite noisy, making ear plugs a welcome accompaniment.  The patient must also remove any jewelry or metal, which could interfere with the test.

When to expect test results

The patient’s doctor usually receives a written report of the MRI results within ten days of the test.

How an MRI scan is different

MRI scans do not subject the body to radiation exposure, as do traditional X–rays and CT scans.  In addition, the MRI scans differentiate among the different tissues and organs in the body by assigning each a different color, while CT scans show such differentiation only with light and dark shading.  Thus, the MRI gives physicians a clearer picture of the body’s interior, which is useful in the early detection of tumors. 

Some doctors use MRI scans for mesothelioma patients who may benefit from surgery to gain as much information as possible about the spread of the tumor.  These doctors often point to the MRI scan’s heightened ability to show that a tumor has invaded the area of the diaphragm.  Other physicians feel that the MRI images are not sufficiently better than CT scans to make a difference for purposes of surgery. 

Combination Scans

The most powerful scanning techniques used today actually combine at least two of the procedures described above.  Many medical facilities are using imaging devices with PET scanners and CT scanners housed in the same casing, and some are even combined with MRI.  The advantage to the combination approach is that it allows a comparison of the biochemical processes, which are shown in a PET scan, with the anatomical changes displayed in the CT scan.  The procedure for both scans happens almost simultaneously, meaning that the patient does not have to move from one scan to the next.  This stability ensures that the two different types of images align with each other. 

Echocardiogram

Some doctors use an Echocardiogram to explore whether a tumor has invaded the area of the heart. This is the same procedure that many patients are already familiar with, given its frequent use to diagnose the presence of heart disease. Using sound waves that are so high in frequency they cannot be heard, an Echocardiogram provides doctors with valuable information about the size and shape of the heart and its pumping strength.  The procedure will also show the location and extent of any damage to the heart, including damage from mesothelioma. 

Cytology and Biopsy

The physical examination and radiographic images are helpful, but they are not sufficient for a diagnosis of mesothelioma.  They are, at most, preliminary indications of the disease.  If the tests suggest the presence of mesothelioma, a biopsy is necessary to confirm the diagnosis.  A biopsy is a procedure in which tissue is taken from the body for review under a microscope by a pathologist.  The pathologist will determine whether mesothelioma is present and what types of cells are involved.  Once the type of mesothelioma is known, a treatment plan can be established. 

Cytology

In some cases, the examination of individual or small clusters of cells — called cytology or cytopathology — may be used to diagnose mesothelioma. These cells are often found in fluid drawn from a patient’s body after a pleural or peritoneal effusion (a build–up of excess fluid).  The fluid is tested for its chemical make up and examined under a microscope by a pathologist, a doctor who is an expert in diagnosing cancer.  If cancer cells are found, additional special tests are necessary to determine whether the cancer is a lung cancer, mesothelioma, or another type of cancer.

Compared to a needle biopsy, a cytology specimen is easier to obtain, results in less discomfort to the patient, reduces the risk of serious complications, and costs less than a tissue biopsy.  Cytology’s big disadvantage is that a biopsy produces much more accurate results.

Biopsy

A biopsy is the removal of a small piece of tissue for laboratory examination.  Several different types of biopsies exist.  A biopsy can be most simply performed with a long hollow needle.  In cases of suspected mesothelioma, however, many biopsies are done surgically.  In a closed (or core) biopsy, the surgeon uses a small surgical incision to insert a camera–like instrument.  This instrument can be used to see the area, and helps guide the surgeon to the appropriate place to take the sample.  An open biopsy is performed in a hospital while the patient is asleep, after receiving general anesthesia.  A surgeon makes a cut into the affected area, and the tissue is removed.

Needle Aspiration Biopsy/Fine Needle Aspiration (FNA)/Fine Needle Aspiration Cytology

The simplest form of diagnostic biopsy is called needle aspiration biopsy (also called fine needle aspiration or fine needle aspiration cytology).  Many surgeons prefer the needle biopsy to other procedures because it is quick and safe.  The technique is most commonly used for cancers located close to the skin’s surface, but needle aspiration biopsy is also employed to diagnose mesothelioma. The surgeon uses a long, hollow needle to extract tissue from the area of concern.  The surgeon performing a needle biopsy will often use a CT scan as a guide to the proper area.  The procedure is also called Fine Needle Aspiration Cytology because some physicians consider it to be a cytology test rather than a biopsy.

Thoracoscopy

A thoracoscopy is a procedure that may be used when pleural mesothelioma is suspected.  The surgeon makes one or two small incisions between the patient’s ribs to insert a thoracoscope — a tube with a miniscule video camera attached.  The surgeon enters the chest cavity and, with the aid of the video camera, uses special forceps to remove a tissue biopsy.  This procedure is often called video–assisted thoracoscopic surgery (VATS).  The pleural biopsy is performed under general anesthesia.  The small incisions must be placed somewhere on the chest where they can be incised because tumor cells have the potential to contaminate any incision.

Bronchoscopy

If the patient appears to have pleural mesothelioma, the physician may also perform a bronchoscopy.  In this type of biopsy, a flexible lighted tube is placed into the patient’s mouth, down the trachea, and then into the bronchi to look for any tumors in the airway.  Small samples of any tissue that appears abnormal can be extracted for testing.

Laparoscopy

A laparoscopy is often performed when peritoneal mesothelioma is suspected.  In this procedure, the surgeon makes one or two tiny incisions in the patient’s abdomen, through which a laparoscope (a flexible tube with a small video camera attached) is inserted into the abdominal cavity.  Using special surgical tools, the surgeon is then able to remove a small piece of any tumor for examination. 

Thoracotomy

Thoracotomy is more invasive than thoracoscopy.  It requires the surgeon to open the patient’s chest between the ribs to search for signs of disease.  During the surgery, a tissue sample is extracted for testing. 

Laparotomy

Laparotomy is a surgical procedure in which the patient’s abdomen is cut open and a sample of tissue removed for testing. 

Mediastinoscopy

A mediastinoscopy is sometimes performed to determine if a tumor has spread to the lymph nodes in the center of the chest.  The lymph nodes are bean–sized groups of immune system cells that help fight off infections and cancers. The greater the involvement of the lymph nodes, the greater the stage of the cancer.  A mediastinoscopy is a surgical procedure in which a lighted tube (mediastinoscope) is inserted under the chest bone at neck level and then manipulated down into the chest.  This allows the surgeon to see the lymph nodes and remove samples to check for mesothelioma.  As with the pleural biopsy, the mediastinoscopy is performed when the patient is completely asleep, under general anesthesia.

Cytology and Biopsy Sample Testing

After the suspect cells are removed from the body either through biopsy or cytology, a pathologist analyzes the material to determine if mesothelioma is present.  A pathologist is a doctor who has specialized training and experience in analyzing abnormal cell growth and in diagnosing diseases.  A number of methods can be employed to analyze the cells, but the customary procedure is this:  The pathologist removes a very fine layer of tissue from the sample; places the material on a microscope slide; colors the tissue with dye to make the cells more visible; and seals the slide to allow its scrutiny under the microscope. 

It is not easy to diagnose mesothelioma simply by examining cells taken from cytology fluid.  The disease can even be difficult to diagnose from tissue samples taken by needle biopsy.  Under the microscope, the disease appears the same as several other types of cancer.  Pleural mesothelioma, for example, may resemble lung cancer and peritoneal mesothelioma sometimes looks like cancer of the ovaries.  Accordingly, special laboratory tests are often relied upon to distinguish mesothelioma from other cancers.  This is true regardless of the means by which the tissue was obtained. 

These tests employ special means of recognizing certain types of chemicals (called “markers”) that are contained in mesotheliomas. Immunohistochemistry is a test that searches for particular proteins on the surface of the cells.  This test is used to distinguish between pleural mesothelioma and lung cancer.  A more recent test, called DNA Microarray analysis, focuses on the genetic material in the different cancers.  Mesotheliomas display different gene patterns than do other cancers, allowing the cancers to be distinguished genetically.

The electron microscope also can sometimes assist in the diagnosis of mesothelioma. This high–powered microscope is able to increase the magnification of tissue samples over 100 times greater than the microscope customarily used for cancer diagnosis.  The greater magnification makes it possible to view the parts of mesothelioma cells that distinguish them from other types of cancer cells. 

If a cancer is diagnosed as mesothelioma, the biopsy material is also useful to allow the pathologist to examine whether the disease has spread to other parts of the body.  When a tumor is removed from the body, the pathologist carefully studies the margins to see if cancer cells are present. Tissue with “negative margins” means that the cancer was probably contained within the margins of the tissue removed; if the tissue has “positive margins,” then it is likely that the cancer was not completely removed from the patient.  In the case of mesothelioma, which spreads rapidly, doctors often are concerned that the cancer will spread, or metastasize.  Thus, they may conduct additional tests, including additional biopsies and X–rays, on parts of the body commonly affected by the disease, such as the lymph nodes.

Mesomark — Mesothelioma Blood Test

Mesothelioma might be a more treatable disease if the cancer could be diagnosed in its earlier stages.  But because mesothelioma symptoms do not usually appear for decades after a patient’s exposure to asbestos, most patients are diagnosed after the disease has already reached Stage III or IV.  Because the cancer is so aggressive at that point, treatment options usually focus more on maintaining a decent quality of life for the patient than actually curing the disease. 

If, however, mesothelioma could be diagnosed earlier, mesothelioma patients would have a much better prognosis.  A relatively new mesothelioma blood test called Mesomark claims to make such early diagnosis possible.  Mesomark was developed by the Pennsylvania company Fujirebio Diagnostics Inc., which specializes in oncology testing.  The United States Food and Drug Administration approved the blood test in January 2007.

Mesomark is a simple blood test that employs an enzyme–linked immunosorbent assay to measure the level of Soluble Mesothelin–Related Peptides (SMRP) in human serum.  SMRP is a biomarker produced by mesothelioma cells, which biomarker may be increased in the serum of mesothelioma patients.  Certain levels of SMRP are high enough to indicate the existence of mesothelioma.

The detection of the biomarker SMRP through a blood test can assist in an early diagnosis of mesothelioma, giving patients more treatment options and a brighter prognosis.  In addition, the Mesomark blood test may also be useful to track the success of treatments in mesothelioma patients who have already been diagnosed. 

Researchers at New York University reported in February 2007 that SMRP is in fact a valid biomarker for mesothelioma.  Dr. Harvey Pass of NYU’s School of Medicine and a team of cardiothoracic experts studied Mesomark with the serum and pleural effusions of mesothelioma patients.  The results of the study showed that patients with mesothelioma had significantly higher levels of SMRP in their blood than people in the control group, who also had asbestos exposure and other forms of cancer.

Staging and Prognosis

After a diagnosis of mesothelioma or lung cancer is confirmed, physicians will next investigate the stage of the disease.  Doctors use staging to describe the extent of the disease, including the size of the tumor and whether, or how far, it has spread.  By learning the stage of the disease, doctors can chart a course of treatment and evaluate its effectiveness over time.  Staging also affects a patient’s prognosis.

CT scans and MRI scans are frequently used to discover whether a cancer has spread.  In cases of pleural mesothelioma, doctors often rely on a mediastinoscopy to learn whether the cancer has moved to the lymph nodes in the chest. 

Physicians refer to different staging systems for different types of cancer.  Currently, a staging system has been established for pleural mesothelioma (mesothelioma around the lung), but not other types of mesothelioma, such as peritoneal mesothelioma or pericardial mesothelioma.  These forms of mesothelioma are rare and doctors have not studied them as well.  The American Joint Committee on Cancer (AJCC) staging system assigns Roman numerals from I to IV (one to four) for the different stages of pleural mesothelioma.  As a rule, the lower the number, the more contained the tumor.  A higher number generally means that the cancer is more serious and has already spread.  The stages for pleural mesothelioma include:

Stage I. The mesothelioma is localized, meaning that it is limited to a single portion of the chest lining.
Stage II. The tumor may have grown beyond the chest lining to the diaphragm or to a lung.
Stage III. The mesothelioma may have spread to other areas within the chest and to nearby lymph nodes.
Stage IV. The mesothelioma has metastasized (spread) to distant areas.  Commonly, mesothelioma metastasizes to the brain, areas of the lung that are not adjacent to the original tumor, and to lymph nodes in the chest. 

Unfortunately, mesothelioma is not usually diagnosed until the disease has already progressed to the later stages.  This is largely due to the long latency period associated with mesothelioma; symptoms do not generally appear until decades after the first exposure to asbestos.  As a result, the prognosis for a mesothelioma patient is poor.  When a cancer reaches Stage III or IV, there are fewer treatment options available and those are not often effective.  Further, most mesothelioma patients are over the age of 55, though this is not always true.  Because of their age, many patients already have other medical problems, which make treatment of the cancer even more difficult.
 
Although the technical stage at which mesothelioma is diagnosed unquestionably affects a patient’s chances for survival, this does not mean that other factors are not important.  A patient’s prognosis is also determined by the following:

  • The type of mesothelioma — pleural, peritoneal, or pericardial
  • The tumor’s size
  • Whether the tumor’s location allows it to be surgically removed
  • Whether the patient smokes

Other criteria that also affect a patient’s longevity include: chest pain; weight loss; shortness of breath; high white blood cell count; low red blood cell count; high levels of LDH in the blood; and whether the patient is too ill to engage in the normal tasks of daily life. A person who is experiencing all of these factors often does not live more than six months.  But patients with none of the criteria should expect to live at least one year and have a forty per cent chance of living two years.

The American Cancer Society reports that the five–year relative survival rate for mesothelioma patients is approximately ten percent.  This figure represents the percentage of patients who survive for at least five years from the time mesothelioma is diagnosed.  Though the number may seem low, it has actually risen over the last five years; at the end of 2002, the number was nine percent.  In addition, recent studies report that the one–year survival rate for mesothelioma patients is around forty percent today, a number that has similarly risen in the past five years.  During the 1990s, a patient with mesothelioma rarely lived over a year after diagnosis.

 

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