Mesothelioma: Types, Causes, Pathogenesis, Symptoms, Diagnosis, Staging, Treatment and Prevention

Mesothelioma

~Introduction

Mesothelioma is a rare, aggressive, and often fatal malignant tumor arising from the mesothelial cells that line the body's serous cavities, most commonly the pleura (lining of the lungs). Strongly linked to asbestos exposure, mesothelioma has long latency periods, typically developing 20–50 years after exposure. Although medical advancements have improved early diagnosis and treatment options, mesothelioma continues to have a poor prognosis and remains a significant global health concern.

This article provides an in-depth look at the epidemiology, causes, pathology, clinical features, diagnosis, treatment, prevention, and emerging research on mesothelioma.

~Understanding Mesothelioma

Mesothelioma originates from the mesothelium, a thin membrane that lines several cavities:

• Pleura (lungs)

• Peritoneum (abdomen)

• Pericardium (heart)

• Tunica vaginalis (testes)

Among these, pleural mesothelioma accounts for nearly 70–80% of all cases.

~Types of Mesothelioma

Mesothelioma is classified based on its location and cell type.

1. By Location

Pleural Mesothelioma

• Most common type

• Originates in the lining of the lungs

• Associated with breathing asbestos fibers

Peritoneal Mesothelioma

• Involves the abdominal lining

• Causes abdominal pain, swelling, and digestive issues

Pericardial Mesothelioma

• Very rare

• Develops in the lining around the heart

Testicular Mesothelioma

• Extremely rare

• Arises from the tunica vaginalis of the testes

2. By Cell Type

Epithelioid Mesothelioma

• Most common (50–70% of cases)

• Cells grow more slowly and respond better to treatment

Sarcomatoid Mesothelioma

• More aggressive

• Difficult to treat

• Poor prognosis

Biphasic Mesothelioma

• Contains both epithelioid and sarcomatoid cells

• Prognosis varies based on cell ratio

~Causes and Risk Factors

1. Asbestos Exposure (Primary Cause)

Asbestos is a naturally occurring mineral composed of microscopic fibers resistant to heat and chemicals. When inhaled or ingested, these fibers lodge in the mesothelial lining, causing inflammation, scarring, cellular damage, and eventually cancer.

High-risk environments include:

• Construction sites

• Shipyards

• Mining

• Automobile brake manufacturing

• Insulation factories

Workers in these industries often carried fibers home on their clothes, exposing family members (known as secondary asbestos exposure).

2. Other Risk Factors

Radiation Exposure

Prior radiation therapy to the chest or abdomen may increase risk.

SV40 Virus

Some studies suggest a link between simian virus 40 contamination in vaccines in the 1950s–60s and mesothelioma, though evidence remains inconclusive.

Genetic Factors

Mutations in the BAP1 gene increase susceptibility and are associated with earlier onset.

Erionite Exposure

A naturally occurring mineral found in some geographic regions (such as parts of Turkey) is also linked to mesothelioma.

~Pathogenesis

Mesothelioma develops through multiple biological mechanisms:

1. Inflammation
   Asbestos fibers cause chronic inflammation, which promotes DNA damage.

2. Oxidative Stress
   Asbestos generates free radicals that injure mesothelial cells.

3. Genetic and Epigenetic Mutations
   Mutations in genes like BAP1, NF2, and CDKN2A drive malignant transformation.

4. Tumor Microenvironment Alteration
   Fibers alter local immune responses, allowing tumor growth.

~Clinical Presentation

Symptoms depend on the tumor location.

Pleural Mesothelioma Symptoms

• Shortness of breath

• Persistent chest pain

• Pleural effusion (fluid build-up)

• Chronic cough

• Fatigue

• Unexplained weight loss

Peritoneal Mesothelioma Symptoms

• Abdominal swelling (ascites)

• Pain or cramping

• Nausea

• Changes in bowel habits

Pericardial Mesothelioma Symptoms

• Chest pain

• Arrhythmia

• Sweating

• Breathlessness

Testicular Mesothelioma Symptoms

• Scrotal swelling

• Painless mass

Because symptoms are vague and slow to appear, mesothelioma is frequently diagnosed at advanced stages.

~Diagnosis

Diagnosing mesothelioma is challenging due to nonspecific symptoms and resemblance to other diseases.

1. Imaging Studies

Chest X-Ray

May show fluid accumulation or lung abnormalities.

CT Scan

Most frequently used; helps detail tumor size, spread, and pleural thickening.

MRI

Useful for assessing chest wall invasion.

PET Scan

Identifies active cancer cells and metastasis.

2. Fluid Analysis

Thoracentesis or paracentesis can remove pleural or abdominal fluid for testing, but cytology often fails to confirm mesothelioma definitively.

3. Biopsy (Gold Standard)

Accurate diagnosis requires tissue sampling through:

• Thoracoscopic biopsy

• CT-guided core needle biopsy

• Laparoscopic biopsy

Pathologists also use immunohistochemistry markers such as:

• Calretinin

• WT1

• D2-40

• CK5/6

These markers help differentiate mesothelioma from lung adenocarcinoma.

~Staging

Mesothelioma is staged using the TNM system:

• T (Tumor): Size and spread of primary tumor

• N (Nodes): Lymph node involvement

• M (Metastasis): Distant spread

Stages range from I (localized) to IV (extensive metastasis).

~Treatment Options

Treatment depends on type, stage, cell type, and patient health.

1. Surgery

Surgery is most effective in early-stage pleural mesothelioma.

Pleurectomy/Decortication (P/D)

Removal of the pleura while preserving the lung.

Extrapleural Pneumonectomy (EPP)

Removal of:

• Entire lung

• Pleura

• Diaphragm part

• Pericardium part

It is aggressive but may extend survival in select patients.

Cytoreductive Surgery with HIPEC (for Peritoneal)

Tumor removal followed by heated chemotherapy delivered directly into the abdomen.

2. Chemotherapy

First-line treatment typically includes:

• Pemetrexed + Cisplatin
  This combination improves survival and symptom control.

3. Immunotherapy

A major breakthrough in mesothelioma treatment.

Agents include:

• Nivolumab

• Pembrolizumab

• Ipilimumab

These boost immune system response and are especially useful for advanced or inoperable cases.

In 2020, a combination of nivolumab + ipilimumab was approved as first-line therapy for unresectable mesothelioma.

4. Radiation Therapy

Used for:

• Pain control

• Shrinkage of tumor masses

• Post-surgical tumor margin sterilization

Not curative, but helpful in symptom relief.

5. Emerging Treatments

Tumor Treating Fields (TTF)

Employs electric fields to disrupt cancer cell division.

Gene Therapy

Modifies genes to enhance immune response.

Targeted Therapy

Focuses on molecular pathways; still under investigation.

~Prognosis

Mesothelioma generally has a poor prognosis due to late diagnosis.

Average survival:

• Pleural Mesothelioma: 12–21 months

• Peritoneal Mesothelioma: Up to 5 years with HIPEC

• Sarcomatoid type: Shortest survival

• Epithelioid type: Best response to therapy

Factors influencing survival:

• Age

• Cell type

• Stage at diagnosis

• Treatment type

• Genetic mutations (e.g., BAP1 mutation indicates better prognosis)

~Prevention

Since asbestos is the primary cause, prevention focuses on limiting exposure.

1. Workplace Safety

• Use protective equipment

• Follow OSHA guidelines

• Regular air monitoring

2. Home Safety

Older buildings may contain asbestos in:

• Insulation

• Roofing

• Flooring
  Professional removal is essential.

3. Avoid Secondary Exposure

Workers should shower and change clothes before returning home.

~Conclusion

Mesothelioma is a devastating disease with strong links to asbestos exposure, long latency periods, and aggressive behavior. Although it remains difficult to diagnose and treat, advances in immunotherapy, targeted therapies, and surgical techniques are steadily improving outcomes. Preventing asbestos exposure remains the most effective strategy for reducing global mesothelioma cases. Continued research offers hope for better survival and improved quality of life for patients facing this challenging cancer.