Mesothelioma

By definition, Malignant Mesothelioma is an aggressive cancerous disease that affect the thin layer covering the lungs (pleura) mainly, and less commonly or rarely the heart (pericardium), internal abdominal organs (peritoneum) and testicles (tunica vaginalis).

There are four types of malignant mesothelioma based on the location of origin:

• Pleural mesothelioma: arise from the lining of the lungs (Pleura)
• Pericardial mesothelioma: arise from the lining of the heart (Pericardium)
• Peritoneal mesothelioma: arise from the lining of the abdominal cavity (Peritoneum)
• Testicular mesothelioma: arise from the lining of the testicles (Tunica vaginalis)

The most common sites for pleural mesothelioma metastasis, numbers rounded, include:

•  The Liver (56%)
•  The Adrenal glands (31%)
•  The Kidneys (30%)
•  The opposite Lung (27%)
•  The Brain and central nervous system (3%)

Mechanism of mesothelioma development:

How asbestos cause cancer still a research effort to reach a final conclusion. Currently the researchers at the University of Hawai'i Cancer Research Center think that the mechanism by which asbestosis causes malignant mesothelioma is by killing the mesothelial cells through a process called "programmed cell necrosis" that leads to the release of a molecule called high-mobility group box 1 protein (HMGB1). HMGB1 starts a particular type of inflammatory reaction that causes the release of mutagens and factors that promote tumor growth in other live cells.

Researchers found somatic mutations in several genes identified in malignant mesothelioma. These genes include:

WT1 (607102) on chromosome 11p13
BCL10 (603517) on chromosome 1p22
CDKN2A (600160) on chromosome 9p21
NF2 (607379) on chromosome 22q12
BAP1 (603089) on chromosome 3p21

Abstract from OMIM.

Causes of mesothelioma include:

1- Asbestos
2- Winchite
3- Richterite
4- Erionite
5- Taconite
6- Radiation
7- Inflammation
8- Simian Virus 40 (possible role)
9- Idiopathic cases especially in children

Mesothelioma is classified into 3 major histological types based on cell type; other rare types do exist:

1- Epithelioid type: consist of 60% of cases: cells appear more square-shaped with visible nuclei and form prominent Papillo-tubular structures.



2- Sarcomatoid type: consist of 20% of cases: cells appear spindle-shaped with elongated nuclei and form proliferative pattern that mimic sarcoma.



3- Biphasic type: consist of about 20% of cases: cells are mixture of epithelial cells and sarcomatoid cells that form one tumor with mixed features of epithelioid mesothelioma and that of sarcomatoid mesothelioma.



4- Desmoplastic type rare and might consist up to 1-2% of cases. This type has the dominant feature of granulation or fibrous pleuritis.

5- Special variants that only appear sporadically:

 (a) Lymphohistiocytoid mesothelioma
 (b) Deciduoid mesothelioma
 (c) Anaplastic mesothelioma
 (d) Well differentiated papillary mesothelioma
 (e) Others

Images courtesy of NLM (National Library of Medicine).

The Differential Diagnosis of Mesothelioma depends on the type and location as following:

1- Pleural epithelioid mesothelioma: 

          a- Adenocarcinoma of the Lung
          b- Metastatic adenocarcinoma involving the pleura
          c- Reactive mesothelial hyperplasia

2- Peritoneal epithelioid mesothelioma: 

          a- Serous papillary adenocarcinoma of the ovary
          b- Serous carcinoma of the peritoneum

3- Pleural sarcomatoid mesothelioma: 

           a- Sarcomatoid carcinoma of the lung
           b- Sarcoma of the pleura, lungs or chest wall

4- Peritoneal sarcomatoid mesothelioma: 

          a- Sarcoma of the peritoneum, intestines or abdominal wall

5- Pleural desmoplastic mesothelioma: 

          a- Fibrous Pleuritis

6- Pleural biphasic mesothelioma: 

          a- Carcinosarcoma or pulmonary blastoma of the lung
          b- Biphasic synovial sarcoma of the pleura

7- Peritoneal biphasic mesothelioma: 

          a- Carcinosarcoma of the ovary or uterus

How long it take for mesothelioma to develop after asbestos exposure?

Mesothelioma related to asbestos exposure take a long time to develop. The time between first exposure to asbestos and diagnosis of mesothelioma is usually between 20 and 50 years. The risk of mesothelioma does not go down over time after the exposure to asbestos stops. The risk appears to be lifelong.

The risk factors for mesothelioma include Asbestos, Zeolites, Radiation, SV40 virus, Age and Gender.

Asbestos
The main risk factor for pleural mesothelioma is exposure to asbestos which is a group of minerals that occur naturally as bundles of tiny fibers found in soil and rocks in many parts of the world. If asbestos fibers in the air are inhaled they can then injure the cells of the pleura, and eventually cause mesothelioma. Asbestos fibers can also damage cells of the lung and result in asbestosis (scar tissue in the lung) and/or lung cancer. Peritoneal mesothelioma, which forms in the abdomen, can result from coughing up and swallowing inhaled asbestos fibers. Family members of people exposed to asbestos at work can also be exposed because the workers can carry home asbestos fibers on their clothes.


Zeolites
Zeolites are minerals chemically related to asbestos. An example is erionite, which is common in the rocks and soil in parts of Turkey. High mesothelioma rates in these areas are believed to be caused by exposure to this mineral.

Radiation
There have been a few published reports of mesotheliomas that developed after people were exposed to high doses of radiation to the chest or abdomen as treatment for another cancer. Although the risk of mesothelioma is higher in patients who have been treated with radiation, this cancer is still rare in these patients.

There have also been reports linking mesothelioma to injections of thorium dioxide (Thorotrast). This radioactive material was used by doctors for certain x-ray tests until the 1950s. Thorotrast was found to cause cancers, so it has not been used for many decades.

SV40 virus
Some studies have raised the possibility that infection with simian virus 40 (SV40) might increase the risk of developing mesothelioma. Some injectable polio vaccines given between 1955 and 1963 were contaminated with SV40. As many as 30 million people in the United States may have been exposed to this virus.

Age
The risk of mesothelioma increases with age. Mesothelioma can occur in young people (even children), but it is rare in people under age 45. About 2 out of 3 people with mesothelioma of the chest are 65 or older.

Gender
Mesothelioma is much more common in men than in women. This is probably because men have been more likely to work in jobs with heavy exposure to asbestos.

Abstracted from the American Cancer Society.

What is the prognosis of Mesothelioma?


The prognosis of mesothelioma vary based on several factors, the most important 3 are the Type, the Stage and the Age. The average survival rate is about 1 year from the time of diagnosis. Average of 20% will live 2 years, but this will vary based on the stage as shown in this post.


What are the factors affecting mesothelioma prognosis?


There are several factors that affect prognosis in mesothelioma patients which include:
Cell type, Location, Stage, Age, treatment, LDH level, CBC levels (WBCs, RBCs and platelets) and Health condition.


Cell type: Epithelioid mesothelioma has a better prognosis than sarcomatoid or biphasic mesothelioma.


Location: Pericardial mesothelioma has the worst prognosis followed by the pleural type, with the peritoneal type having better prognosis.


Stage: Earlier diagnosed patients will have better prognosis especially if the treatment modalities started soon. The earlier (lowest) the stage, the better the prognosis. Stage I carry the best prognosis.

According to the American cancer society, the 2-year and 5-year survival rates, by stage, for malignant pleural mesothelioma:

For stage IA cancers, the 2-year survival rate is about 46%, and the 5-year survival rate is about 16%.
For stage IB cancers, the 2-year survival rate is about 41%, and the 5-year survival rate is about 13%.
For stage II cancers, the 2-year survival rate is about 38%, and the 5-year survival rate is about 10%.
For stage IIIA cancers, the 2-year survival rate is about 30%, and the 5-year survival rate is about 8%.
For stage IIIB cancers, the 2-year survival rate is about 26%, and the 5-year survival rate is about 5%.
For stage IV cancers, the 2-year survival rate is about 17%, and the 5-year survival rate is less than 1%.

Age: The 5-year survival rates for mesothelioma from statistics from the National Cancer Institute (NCI):

44.2 percent for patients 45 years old or younger.
15.6 percent for patients between the ages 45 – 54.
15.9 percent for patients less than 65.
5.1 percent for patients over 65.


Treatment: This will increase the life expectancy based on the type, location and stage. Studies showed that some treatments can increase the survival rates.


Health condition: The younger and healthier the patient is, the better response to treatment occurs as these patients' bodies can tolerate chemotherapy or other major invasive procedures.

What is the survival rate for mesothelioma?

According to the American cancer society, the 2-year and 5-year survival rates, by stage, for malignant pleural mesothelioma:

For stage IA cancers, the 2-year survival rate is about 46%, and the 5-year survival rate is about 16%.
For stage IB cancers, the 2-year survival rate is about 41%, and the 5-year survival rate is about 13%.
For stage II cancers, the 2-year survival rate is about 38%, and the 5-year survival rate is about 10%.
For stage IIIA cancers, the 2-year survival rate is about 30%, and the 5-year survival rate is about 8%.
For stage IIIB cancers, the 2-year survival rate is about 26%, and the 5-year survival rate is about 5%.
For stage IV cancers, the 2-year survival rate is about 17%, and the 5-year survival rate is less than 1%.


The 5-year survival rates for mesothelioma from statistics from the National Cancer Institute (NCI):

44.2 percent for patients 45 years old or younger.
15.6 percent for patients between the ages 45 – 54.
15.9 percent for patients less than 65.
5.1 percent for patients over 65.