Mesothelioma is a rare and aggressive cancer originating in the mesothelium, a protective lining around internal organs. While it most commonly affects the pleura (lining of the lungs), it can also develop in the peritoneum (lining of the abdomen), the pericardium (lining of the heart), and, rarely, the tunica vaginalis (lining of the testes). This disease is strongly linked to asbestos exposure, which often occurs decades before symptoms appear.
How Mesothelioma Develops
Mesothelioma develops due to exposure to asbestos fibers. These microscopic fibers, when inhaled or ingested, can become lodged in the mesothelial lining of organs like the lungs or abdomen. The body’s immune system attempts to remove these foreign fibers, leading to chronic inflammation.
Over a latency period of 20 to 40 years, this persistent irritation can lead to cellular changes. Prolonged exposure damages DNA within normal mesothelial cells, disrupting their growth control. Genetic alterations can activate oncogenes, promoting uncontrolled cell growth, or inactivate tumor suppressor genes, which prevent cancer development.
The accumulation of these genetic changes transforms healthy mesothelial cells into malignant ones. As cancerous cells proliferate, they form tumors that can spread locally along mesothelial surfaces.
Key Pathological Types
Mesothelioma is classified into histological types based on the appearance of its cancer cells under a microscope. These distinctions influence disease progression and treatment response. The three types are epithelioid, sarcomatoid, and biphasic.
Epithelioid mesothelioma is the most common type, accounting for approximately 70% of cases. These cells resemble glandular cells and grow in sheets or tubules. This type is less aggressive and responds better to treatment, leading to a better prognosis.
Sarcomatoid mesothelioma is characterized by spindle-shaped cells, resembling those found in sarcomas, and makes up about 10-20% of cases. This type is aggressive and has a poorer prognosis. Its distinct cellular morphology makes it challenging to treat.
Biphasic mesothelioma contains a mixture of both epithelioid and sarcomatoid cells, accounting for about 20-30% of diagnoses. The prognosis for biphasic mesothelioma depends on the predominant cell type; tumors with a higher proportion of epithelioid cells respond more favorably to treatment.
Diagnosing Mesothelioma
Diagnosing mesothelioma relies on obtaining and analyzing tissue samples. Biopsy procedures, such as thoracoscopy, pleuroscopy, or CT-guided biopsy, collect tissue from the affected lining. Pathologists examine these samples under a microscope to identify characteristic cancerous mesothelial cells.
Microscopic examination is important for distinguishing mesothelioma from other cancers, particularly adenocarcinoma, which can appear similar. Pathologists look for specific cellular features and growth patterns unique to mesothelioma. However, relying solely on morphology can be challenging due to the varied appearance of mesothelioma cells.
Immunohistochemistry (IHC) is a specialized staining technique that aids diagnosis. It uses antibodies to detect specific proteins within cells, helping to confirm mesothelioma and differentiate it from other malignancies. Mesothelioma cells show positive staining for markers such as calretinin, WT-1, and cytokeratin 5/6, while testing negative for markers like CEA and TTF-1, often present in adenocarcinomas.
Molecular testing is also used in diagnosing mesothelioma. For instance, the loss of BAP1 protein expression or CDKN2A homozygous deletion, detected through techniques like immunohistochemistry or FISH (fluorescence in situ hybridization), are specific indicators of malignancy in mesothelial lesions. These molecular markers provide additional confirmation and offer insights into the disease’s likely progression.
Prognosis and Disease Progression
The pathological findings of mesothelioma significantly influence its prognosis and progression. The histological type is a major factor in determining patient outlook. Epithelioid mesothelioma has a more favorable prognosis compared to sarcomatoid or biphasic types, due to its slower growth rate and better response to therapies.
Mesothelioma begins by spreading locally within the mesothelial lining of the affected organ. For pleural mesothelioma, small nodules may form on the outer pleural layer, gradually extending along the surface and causing the pleural layers to adhere. As the disease progresses, the tumor can encase the entire lung.
The disease stage at diagnosis also plays a significant role in prognosis. Staging is determined by factors such as tumor size, involvement of nearby lymph nodes, and whether it has metastasized to distant sites. Imaging studies are used with pathological findings to determine the stage. An earlier stage at diagnosis is associated with a better prognosis.
Other factors, such as patient health, age, and treatment response, also influence the outcome. While mesothelioma is an aggressive cancer, advances in treatment options are explored to extend survival and improve patient quality of life.