Mesothelioma

Mesothelioma is a malignant neoplasm that develops from the mesothelium tissue (a membrane that covers the internal organs present in the body).  It occurs very rarely and is more frequently caused by inhaling asbestos dust.  The incidence of the disease is slowly on the rise.  In the US, about 2000 new cases are reported every year.  About 70 to 80% of all cases with mesothelioma report exposure to asbestos (NCI, 2002).  Mesothelioma can develop in various sites of the body including the pleura (membranes that covers the lungs), peritoneum (membrane that covers the abdominal cavity), tunica vaginalis testis (membrane that covers the male internal reproductive organs) and tunica serosa uteri (membrane that covers the female internal reproductive organs) (NCI, 2002).

It is made up of one layer of flat or cuboidal cells that surround a particular organ or an organ set belonging to a particular group (Weitz & Luxenberg, 2006).  In between these membranes a fluid is present that permits some amount of movement during physiologic functioning.  When the asbestos is inhaled, it gets deposited into parenchyma of the lungs from where it enters the immediate membrane that covers the lungs.  It may be carried soon to the other membrane of the lung.  The tumor usually begins as discrete plaques known as ‘malignant mesothelial plaques’ (Weitz & Luxenberg, 2006).

These discrete masses soon combine to form a large sheet like lesion that spreads.  The exact process by which mesothelioma occurs is not understood clearly, however, it seems that chronic irritation of the membrane plays a very important role (Weitz & Luxenberg, 2006).  The chromosomes present in the cell are distorted (Tan, 2007).  One of the most frequent changes in the malignant cell was the loss of a copy of Chromosome 22.

The chromosomal picture of the cell seems to be very complex (complex karyotype) and is rearranged (Tan, 2007).  Sometimes, the chromosome arms of 1p, 3p, 9p and 6q may also get structurally rearranged.  This may be brought about by close contact between the chromosomes or the structural proteins with the asbestos particles (Weitz & Luxenberg, 2006).

The asbestos may get deposited in the peritoneum either through the lymphatic system or the due ingestion of the sputum from the lungs (Weitz & Luxenberg, 2006).  The long thin fibers of asbestos are more dangerous than the feathery fibers as they more easily cause cancer.  Once the fibers get deposited in the pleura, the cancer development process actually begins.  In experimental rats, it has been observed that when the pleura or the peritoneum are invaded by the asbestos particles, macrophages and the other cells of the body’s defense mechanism accumulate (Weitz & Luxenberg, 2006).

As the disease progresses, the macrophages and immune cells continue to invade the lesion.  Slowly the cells get transformed into malignancy.  Studies have demonstrated that the asbestos particles may directly (through physical interaction) and indirectly (through accumulation of macrophages) bring about malignant transformation of the epithelium cells.  Indirectly, the macrophages begin to function abnormally.  They phagocyte the asbestos particles and release higher amounts of hydroxyl radicals.

They may stimulate the cancer process by affecting the DNA present in the cell.  Several other substances are released from the macrophages such as mitogens, growth factors, etc, which may bring about chronic irritation.  They also alter entry of certain substances into the cell (by affecting the membrane) and reducing the effect of antioxidant action within the cells.  Asbestos is also known to suppress the action of the body’s defense mechanism by overcoming the action of the lymphocytes (Weitz & Luxenberg, 2006).

Several structural and functional features have been observed in the cells affected with mesothelioma (which have asbestos particles within the cells): –

1. the suppressor genes against cancers present in the cells may get inactivated when the asbestos fibers enters the cells
2. other cancer-stimulating agents may get activated and affect the cell
3. the DNA of the cell gets altered due to the incorporation of a foreign DNA which encourages cancer formation
4.  the DNA repair enzymes may get stimulated and frequently result in a faulty method of repair
5. the cell terminal processes may become abnormal resulting in immortality
6. the DNA sequence may be added at the ends of the cell which makes the cells immortal and results in abnormal functioning (Weitz & Luxenberg, 2006)

References

1. NCI. Mesothelioma: Questions and Answers. 2002. NCI. 5 Apr. 2007 http://www.cancer.gov/cancertopics/factsheet/Sites-Types/mesothelioma
2. Tan W.W. “Mesothelioma.” 2007. E-Medicine. 5 Apr. 2007 http://www.emedicine.com/med/topic1457.htm
3. Weitz & Luxenberg. “The Pathophysiology of Mesothelioma.” 2006. Weitz & Luxenberg Inc. 5 Apr. 2007 http://www.weitzlux.com/mesothelioma/Pathophysiology_403723.html