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What is mesothelioma?
Malignant mesothelioma is an uncommon, but no longer rare, cancer
that is difficult to diagnose and poorly responsive to therapy.
Malignant mesothelioma is the most serious of all asbestos-related
diseases. A layer of specialized cells called mesothelial cells
lines the chest cavity, abdominal cavity, and the cavity around
the heart. These cells also cover the outer surface of most internal
organs. The tissue formed by these cells is called mesothelium.
The mesothelium helps protect the organs by producing a special
lubricating fluid that allows organs to move around. For example,
this fluid makes it easier for the lungs to move inside the chest
during breathing. The mesothelium of the chest is called the pleura
and the mesothelium of the abdomen is known as the peritoneum. The
mesothelium of the pericardial cavity (the "sac-like" space around
the heart) is called the pericardium.
Tumors of the mesothelium can be benign (noncancerous) or malignant
(cancerous). A malignant tumor of the mesothelium is called a malignant
mesothelioma. Because most mesothelial tumors are cancerous, malignant
mesothelioma is often simply called mesothelioma. Mesothelioma was
recognized as a tumor of the pleura, peritoneum and pericardium
in the late 1700's. However it was not until much later, in 1960,
that this particular type of tumor was described in more detail
and even more importantly, its association with asbestos exposure
was recognized. The first report linking mesothelioma to asbestos
exposure was written by J.C.Wagner, and described 32 cases of workers
in the "Asbestos Hills" in South Africa. Since than the relationship
between mesothelioma and asbestos exposure has been confirmed in
studies around the world.
The incidence of mesothelioma in the United States remains very
low, with 14 cases occurring per million people per year. Despite
these numbers the noticed threefold increase in mesothelioma in
males between 1970 and 1984, is directly associated with environmental
and occupational exposure to asbestos, mostly in areas of asbestos
product plants and shipbuilding facilities. Although the disease
is much more commonly seen in 60-year old men, it has been described
in women and early childhood as well. The cause of the disease is
not so well understood in these latter two groups, but there is
some evidence of possible asbestos exposure for some of these cases
as well. Malignant mesotheliomas are divided into three main types.
About 50% to 70% of mesotheliomas are the epithelioid type. This
type has the best prognosis (outlook for survival).
The other two types are the sarcomatoid type (7%-20%), and the mixed/biphasic
type (20%-35%). Treatment options for all three types are the same.
About three-fourths of mesotheliomas start in the chest cavity.
They are known as pleural mesotheliomas. Another 10% to 20% begin
in the abdomen. These are called peritoneal mesotheliomas. Pericardial
mesotheliomas, those starting in the cavity around the heart, are
very rare. The covering layer of the testicles is actually an outpouching
of peritoneum into the scrotum. Mesotheliomas that affect this covering
of the testicles are quite rare.
What are the key statistics about mesothelioma?
is fairly rare. There are an estimated 2,000 to 3,000 new cases
per year of mesothelioma in the United States, but this figure appears
to be increasing. The average age at diagnosis is 50 to 70 years
old. The disease affects men 3 to 5 times more often than women.
Mesothelioma is less common in African Americans than in white Americans.
Mesothelioma is a serious disease. By the time the symptoms appear
and cancer is diagnosed, the disease is often advanced. The average
survival time is about one year. However, if the cancer is found
early and treated aggressively, almost half of the patients whose
cancer is found early reach the two-year mark, and about 20% survive
five years. The 5-year survival rate refers to the percent of patients
who live at least 5 years after their cancer is diagnosed. Many
of these patients live much longer than 5 years after diagnosis,
and 5-year rates are used to produce a standard way of discussing
prognosis. Five-year relative survival rates exclude from the calculations
patients dying of other diseases, and are considered to be a more
accurate way to describe the prognosis for patients with a particular
type and stage of cancer. Of course, 5-year survival rates are based
on patients diagnosed and initially treated more than 5 years ago.
Improvements in treatment often result in a more favorable outlook
for recently diagnosed patients.
What are the different types of mesothelioma?
Pleural Mesothelioma Pleural mesothelioma spreads within the
chest cavity, sometimes involving the lung. Metastases can occur
in any organ, including the brain, and are much more common than
previously thought. The onset of mesothelioma is usually very slow,
the most common presenting symptom is persistent pain localized
in the chest. Sometimes the pain is accompanied by severe difficulty
breathing, due to an accumulation of fluid in the pleural space
known as pleural effusion. Cough, weight loss and fever are not
uncommon. The most valuable single test to show the extent of the
disease is a computed chest tomograph (CT-scan). There are currently
no serum markers available for the diagnosis of mesothelioma. The
detection of elevated serum levels of hyaluronic acid may be useful
in differentiating mesotheliomas from other tumors, or to follow
the effect of treatment. The median survival is about 17 months
from the beginning of symptoms. The 3-year survival is 10% the 5-year
survival is approximately 5% ( if 100 patients are diagnosed with
mesothelioma at a specific point in time, that means that 10 patients
will still be alive at the end of 3 years and 5 patients will only
be alive at the end of 5 years).
Peritoneal Mesothelioma Peritoneal mesothelioma involves the
abdominal cavity, infiltrating the liver, spleen or the bowel. As
with pleural mesothelioma pain is the most common presenting complaint.
In addition, due to fluid accumulation in the abdominal cavity (ascites),
the abdomen appears enlarged. The patients experience nausea, vomiting,
swelling of their feet, fever and difficulty in moving their bowels.
The prognosis is poorer than for pleural mesothelioma with a median
survival time of about 10 months from the onset of symptoms.
Benign Mesothelioma: A rare form of mesothelioma is the cycstic
mesothelioma of the peritoneum. Its prognosis is benign. Its occurrence
has been described primarily in young women. However the diagnosis
presents difficulties, requiring extensive electron miscroscopy
and immunohistochemical studies.
Rare Sites: Mesothelioma of the pericardium, is a very seldom
seen cardiac cancer. The mass is usually detected at a late stage
by echocardiography, the prognosis is very poor , with or without
therapy. Mesothelioma of the ovaries and the scrotum have also been
reported in the literature. The management differs based on the
stage of the disease, the prognosis is also very poor. The etiology
of the few cases of mesothelioma described in children remains unclear
and is not believed to be asbestos-related, the therapy and prognosis
differ on an individual basis.
What are the risk factors for malignant mesothelioma?
A risk factor is anything that increases a person's chance of getting
a disease such as cancer. Different cancers have different risk
factors. For example, unprotected exposure to strong sunlight is
a risk factor for skin cancer and smoking is a risk factor for lung
cancer as well as other types of cancer. Scientists have found several
risk factors that make a person more likely to develop mesothelioma.
Asbestos: The main risk factor for developing mesothelioma is
exposure to asbestos. Asbestos refers to a family of magnesium-silicate
mineral fibers. In the past, asbestos was used widely for insulation
because it does not conduct heat well and it is resistant to melting
or burning. As the link between asbestos and mesothelioma has become
well known, the use of this material has decreased. However, up
to 8 million Americans may already have been exposed to asbestos.
According to the United States Environmental Protection Agency,
as many as 733,000 schools and public buildings in the country today
contain asbestos insulation. As many as 10% to 15% of schools in
the United States may contain asbestos insulation. People who
may be at risk for occupational asbestos exposure include some miners,
factory workers, insulation manufacturers, railroad workers, ship
builders, gas mask manufacturers, and construction workers, particularly
those involved with installing insulation. Several studies have
shown that family members of people exposed to asbestos at work
have an increased risk of developing mesothelioma, because asbestos
fibers are carried home on the clothes of the workers. There are
two main forms of asbestos -- serpentine and amphiboles. Serpentine
fibers are curly and pliable. Chrysotile is the only type of serpentine
fiber and it is the most widely used form of asbestos. Amphiboles
are thin, rod-like fibers of which there are 5 main types-crocidolite,
amosite, anthrophylite, tremolite, and actinolyte. Amphiboles (particularly
crocidolite) are considered to be the most carcinogenic (cancer-causing).
However, even the more commonly used chrysotile fibers have been
associated with malignant (cancerous) mesotheliomas and should be
considered dangerous as well. It may be that asbestos causes cancer
by physically irritating cells rather than by a chemical effect.
When fibers are inhaled, most are cleared in the nose, throat, trachea
(windpipe), or bronchi (large breathing tubes of the lungs). Fibers
are cleared by sticking to mucus inside the air passages and being
coughed up or swallowed. The long, thin, fibers are less readily
cleared, and they may reach the ends of the small airways and penetrate
into the pleural lining of the lung and chest wall. These fibers
may then directly injure mesothelial cells of the pleura, and eventually
Asbestos fibers can also damage cells of the lung and result in
asbestosis (formation of scar tissue in the lung), and/or lung cancer.
The risk of lung cancer among people exposed to asbestos is increased
by 7 times, compared with the general population. Indeed, asbestosis,
mesothelioma, and lung cancer are the three most frequent causes
of death and disease among people with heavy asbestos exposure.
Peritoneal mesothelioma, which forms in the abdomen, may result
from coughing up and swallowing inhaled asbestos fibers. Cancers
of the larynx, pancreas, esophagus, colon, and kidney have also
been linked to asbestos exposure, but the increased risk is not
as great as with lung cancer.
The risk of developing a mesothelioma is related to how much asbestos
a person was exposed to and how long this exposure lasted. People
exposed at an early age, for a long period of time, and at higher
levels are most likely to develop this cancer. Mesotheliomas take
a long time to develop. The time between exposure to asbestos and
diagnosis of mesothelioma is usually between 20 and 40 years. Although
the risk of developing mesothelioma rises with the amount of asbestos
exposure, it is clear that genetic factors also play a role in determining
who develops the disease. This explains why not all persons exposed
to high levels of asbestos dust develop mesothelioma.
Radiation: There have been a few published reports of pleural
and peritoneal mesotheliomas that developed following exposure to
thorium dioxide (Thorotrast). This material was used in the past
by doctors for certain x-ray tests. Because Thorotrast was found
to cause cancers, it has not been used for many years.
Zeolite: This is a silicate mineral, chemically related to asbestos,
common in the soil of the Anatoli region of Turkey. A few cases
of mesothelioma have been described in this region and may have
been caused by this mineral.
Simian Virus 40 (SV40): This virus has recently been identified
by researchers in human mesothelioma cells, and has been shown to
induce mesothelioma in the animal model. Polio vaccines administered
as a primary prevention measure during 1955 - 1961 have been shown
to be contaminated with SV40. However the implications of these
facts are not totally understood and further research will be needed
to clarify the link between malignant mesothelioma and a viral etiology.
Tobacco: Although tobacco smoking has not been associated with
the development of mesotheliomas, the combination of smoking and
asbestos exposure greatly increases the risk of lung cancer. Asbestos
workers who also smoke have a lung cancer risk 50 to 90 times greater
than that of the general population. More asbestos workers die of
lung cancer than of mesothelioma.
What causes mesothelioma? Asbestos
exposure is the main cause of mesothelioma. After these fibers are
breathed in, they travel to the ends of small air passages and reach
the pleura where they cause physical damage to mesothelial cells
that may result in cancer. In addition, they also cause injury to
lung cells that can result in lung cancer and/or asbestosis (replacement
of lung tissue by scar tissue). If swallowed, these fibers can reach
the abdominal cavity where they have a role in causing peritoneal
mesothelioma. Exposure to asbestos, though mostly occupational,
can also be environmental, or familial by household contamination,
through the work clothes of an asbestos worker for instance. Beginning
15 years after the onset of exposure, about 6% of asbestos workers
die of mesothelioma. In one study of asbestos insulation workers,
the death rate from mesothelioma was 344 times higher than in the
general population. (Selifoff IJ et al. Relation between exposure
to asbestos and mesothelioma. NEJM)
What are the signs and symptoms of mesothelioma?
of mesotheliomas are not specific to the disease. People often ignore
them or mistake them for common, minor ailments. Most people with
mesothelioma have symptoms for only 2 to 3 months before they are
diagnosed. About one-fourth have symptoms for at least six months
prior to their diagnosis. Over half of patients with pleural mesothelioma
have pain in the lower back or at the side of the chest. Many report
shortness of breath. A smaller percentage have trouble swallowing,
cough, fever, sweating, fatigue, and weight loss. Other symptoms
include hoarseness, coughing up blood, swelling of the face and
arms, muscle weakness, and sensory loss. Symptoms of peritoneal
mesothelioma include abdominal (belly) pain, weight loss, nausea,
and vomiting. There may also be a hernia, fluid in the abdominal
cavity or a mass in the abdomen. A person with any of these symptoms
who has been exposed to asbestos should see a doctor right away.
How is mesothelioma diagnosed? If
there is a reason to suspect you may have a mesothelioma, the doctor
will use one or more methods to find out if the disease is really
Medical history and physical examination: A complete medical
history (interview) is taken to check for risk factors and symptoms.
This will include questions to determine if you have been exposed
to asbestos. A physical exam will provide information about signs
of mesothelioma and other health problems. Patients with pleural
mesotheliomas (mesotheliomas of the chest) often have pleural effusion
(fluid in their chest cavity) caused by the cancer. Ascites (fluid
in the abdominal cavity) in cases of peritoneal mesothelioma, and
pericardial effusion (fluid in the pericardium) in cases of pericardial
mesothelioma can also be detected during a physical exam.
Imaging tests: A chest x-ray may show irregular thickening of
the pleura, pleural calcifications (mineral deposits), lowering
of the lung fissures (spaces between the lobes of the lungs), and
fluid in the pleural space. These findings suggest asbestos exposure
leading to the development of a mesothelioma. Imaging studies such
as x-rays, computed tomography (CT) scans, and magnetic resonance
imaging (MRI) scans will help determine the location, size, and
extent of the cancer. The CT scan uses a rotating x-ray beam to
create a series of pictures of the body from many angles. A computer
combines these pictures to produce detailed cross-sectional images
of a selected part of the body. To highlight details on the CT scan,
you may be asked for permission to have a harmless dye injected
into a vein. MRI uses magnetic fields instead of x-rays to create
images of selected areas of the body. As with the CT scan, a computer
generates a detailed cross-sectional image.
Tests of fluid and tissue samples: In patients with a pleural
effusion, a sample of this fluid can be removed by inserting a needle
into the chest cavity. A similar technique can be used to obtain
abdominal fluid and pericardial fluid. The fluid is then tested
to show its chemical make up and viewed under a microscope to determine
whether cancer cells are present. A tissue sample of a pleural or
pericardial tumor can be obtained using a relatively new technique
called thoracoscopy. A thoracoscope (telescope-like instrument connected
to a video camera) is inserted through a small incision into the
chest. The doctor can see the tumor through the thoracoscope, and
can use special forceps to take a tissue biopsy. Similarly, laparoscopy
can be used to see and obtain a biopsy of a peritoneal tumor. In
this procedure, a flexible tube attached to a video camera is inserted
into the abdominal cavity through small incisions on the front of
the abdomen. Fluid can also be collected during thoracoscopy or
Surgery, either a thoracotomy (which opens the chest cavity) or
a laparotomy (which opens the abdominal cavity), allows the surgeon
to remove a larger sample of tumor or, sometimes, to remove the
entire tumor. For patients who might have pleural mesothelioma,
the doctor may also do a bronchoscopy. In this procedure a flexible
lighted tube is inserted through the mouth, down the trachea, and
into the bronchi to see if there are other masses in the airway.
Small samples of abnormal-appearing tissue can be removed for testing.
The patient may also have a mediastinoscopy. A lighted tube is inserted
under the sternum (chest bone) at the level of the neck and moved
down into the chest.
Mediastinoscopy allows the surgeon to view the lymph nodes in this
area and remove samples to check for cancer. Lymph nodes are bean-sized
collections of immune system cells that help the body fight infections
and cancers. Cancers arising in the lung often spread to lymph nodes,
but mesotheliomas rarely do this. Tests of lymph nodes can give
the doctor information on whether a cancer is still localized or
if it has started to spread, and can help distinguish lung cancer
from mesothelioma. It is often hard to diagnose mesothelioma by
looking at the cells from the fluid around the lungs, abdomen or
heart. It is even hard to diagnose mesothelioma with tissue from
biopsies. Under the microscope, mesothelioma can look like several
other types of cancer.
For example, pleural mesothelioma may resemble some types of lung
cancer and peritoneal mesothelioma may resemble some cancers of
the ovaries. For this reason, special laboratory tests are often
done to help distinguish mesothelioma from some other cancers. These
tests often use special techniques to recognize certain markers
(types of chemicals) known to be contained in mesotheliomas. Different
markers are present in cancer of the lung or ovary. The electron
microscope can sometimes be helpful in diagnosing mesothelioma.
This microscope can magnify samples more than 100 times greater
than the light microscope which is generally used in cancer diagnosis.
This stronger microscope makes it possible to see small parts of
the cancer cells that distinguish mesothelioma from other types
The diagnosis of mesothelioma presents problems primarily initially
in the distinction between mesothelioma and other forms of cancer
such as adenocarcinoma or benign, noncancerous pleural inflammation.
The best diagnostic tools at the moment remain the open pleural
biopsy performed during thoracoscopy. This procedure also allows
for direct visualization of the inside of the chest, and information
of involvment of other organs and extension of disease. Other procedures
with lower yields are CT guided pleural biopsy, or blind pleural
biopsy. In addition to the gross appearance of the tumor, pathologists
often rely on a panel of histochemical and immunohistochemical stains
to diagnose or exclude meosothelioma. Currently markers linked to
prognosis of mesothelioma are under study, but have not been validated
for the general use.
How is mesothelioma staged? Staging
is the process of finding out how far the cancer has spread. Staging
of mesothelioma is based on imaging studies such as x-rays, CT scans,
and MRI scans. The treatment and outlook for patients with mesothelioma
largely depends on the stage (extent of spread) of their cancer.
Since pleural mesothelioma occurs most frequently and has been studied
the most, it is the only mesothelioma for which a staging classification
exists. The staging system most often used for mesothelioma is the
Butchart system. This system is based mainly on the extent of the
primary tumor mass, and divides mesotheliomas into stages I through
IV. Butchart Staging System
Mesothelioma is present within the right or left pleura, and may
also involve the lung, pericardium, or diaphragm (the muscle separating
the chest from the abdomen) on the same side. Stage
II: Mesothelioma invades the chest wall or involves the esophagus
(food passage connecting the throat to the stomach), heart, or pleura
on both sides. The lymph nodes in the chest may also be involved.
Stage III: Mesothelioma has penetrated through the diaphragm
into the peritoneum (lining of the abdominal cavity). Lymph nodes
beyond those in the chest may also be involved. Stage IV:
There is evidence of distant metastases (spread through the bloodstream
to other organs).
system has recently been developed by the American Joint Committee
on Cancer (AJCC). This is a TNM system, similar to staging systems
used for most other cancers. T stands for tumor (its size and how
far it has spread to nearby organs), N stands for spread to lymph
nodes and M is for metastasis (spread to distant organs). In TNM staging,
information about the tumor, lymph nodes, and metastasis is combined
in a process called stage grouping to assign a stage described by
Roman numerals from I to IV. Minor differences exist between the AJCC
TNM staging system and the Butchart staging system. TNM Staging
Mesothelioma involves the right or left pleura. It may also have
spread into the lung, pericardium, or diaphragm on the same side.
It has not yet spread to the lymph nodes.
Although the recently
developed TNM classification is the most detailed and precise, the
original Butchart staging system is still used most often to describe
the spread of pleural mesotheliomas. Understanding these staging systems
for mesothelioma is important both for estimating and better understanding
prognosis, and also for assessing therapeutic options. Prognostic
Factors: Because pleural mesothelioma has been better studied
than peritoneal mesothelioma we know more about factors associated
with prognosis for pleural mesothelioma. Younger age at diagnosis,
performance status (functional status) and absence of weight loss
are associated with a more favorable prognosis. Mesotheliomas are
usually of three different cell types (histological analysis): 1)
epithelial cell type - has the most favorable prognosis; 2) fibrosarcomatous
cell type - carries the worst prognosis and 3) mixed cell type - has
an intermediate prognosis.
Stage II: Mesothelioma has spread from the pleura on one side
to the nearby peribronchial and/or hilar lymph nodes next to the
lung on the same side. It may also have spread into the lung, pericardium,
or diaphragm on the same side.
Stage III: Mesothelioma has spread into the chest wall muscle,
ribs, heart, esophagus, or other organs in the chest on the same
side as the primary tumor, with or without spread to subcarinal
and/or mediastinal lymph nodes on the same side as the main tumor.
Subcarinal nodes are located at the point where the windpipe branches
to the left and right lungs. Mediastinal lymph nodes are located
in the space behind the chest bone in front of the heart. Mesotheliomas
with the same extent of local spread as in stage II that have also
spread to subcarinal and/or mediastinal lymph nodes on the same
side are also included in stage III.
Stage IV: Mesothelioma has spread into the lymph nodes in the
chest on the side opposite that of the primary tumor, or directly
extends to the pleura or lung on the opposite side, or directly
extends into the peritoneum, or directly extends into organs in
the abdominal cavity or neck. Any mesothelioma with evidence of
distant metastases (spread to other organs through the bloodstream)
or spread to organs beyond the chest or abdomen is included in this
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