Mesothelioma Explained: Deep Dive into Causes, Diagnosis & Care

Mesothelioma is a rare but serious cancer that usually grows in the pleura—the thin tissue around the lungs. It can also appear in the abdomen (peritoneum), around the heart (pericardium), or near the testicles (tunica vaginalis). Asbestos exposure is its most common cause; this harmful material was once used in many industrial and construction settings. People working around asbestos may breathe in tiny fibers that stay in the body for decades, causing slow but steady damage (Bianchi & Bianchi, 2014). Because it can take 20 to 50 years to appear, the disease often goes undetected until it is advanced.

Definition and Cause

Mesothelioma starts in mesothelial cells. These cells create a protective layer (the mesothelium) around organs. Although the pleura is most affected, the disease can also harm the abdomen, heart lining, or testicular area (ACS, 2023a).

• Asbestos Exposure: Asbestos fibers irritate tissues and may lead to cancer over time. Decades can pass before symptoms show.
• Other Causes:
  • Erionite: A mineral found in some regions (like parts of Turkey) that can cause mesothelioma-like diseases.
  • Radiation: High doses, for instance in certain medical treatments, may contribute to this cancer (Carbone et al., 2019).
  • Genetics: Changes in the BAP1 gene can raise the risk in some families (Testa et al., 2011).

How Common It Is

Mesothelioma is rare. In the U.S., about 3,000 new cases occur each year. Rates vary worldwide, often reflecting past asbestos use. Because of the long latency period, cases still appear even after asbestos is banned (NCI, 2022).

• Gender: Men are more often affected, typically due to jobs with higher asbestos exposure (e.g., shipyards or construction). Women can be exposed indirectly, such as by handling contaminated clothing (Reid et al., 2018).
• Age: Most patients are over 60.
• Global Trends: Where asbestos is still used, mesothelioma rates may rise in the coming years. In places with bans, rates are slowly declining, but it can take time for a noticeable drop (van Gerwen et al., 2019).

How It Develops

Once asbestos or similar fibers (like erionite) enter the body, they often remain lodged in tissues, triggering chronic inflammation and genetic damage (Yang et al., 2021). Over time, key genes—such as BAP1, NF2, and CDKN2A—may mutate, allowing cells to grow uncontrollably (Testa et al., 2011). In pleural mesothelioma, a thick “rind” of tumor can form around the lungs. In peritoneal mesothelioma, tumors spread across the abdomen. Eventually, these cells can invade deeper tissues and travel to other body parts.

Main Risk Factors

1. Occupational Asbestos Exposure
   • Jobs in shipyards, construction, or insulation are well-known for high exposure.
   • The inhalation of asbestos dust is the main route of contact.
2. Environmental Exposure
   • Living near asbestos mines or deposits.
   • Contact with erionite in certain geographic areas.
3. Para-Occupational Exposure
   • Family members washing the dusty clothes of workers.
   • People living near industrial sites can also be affected.
4. Radiation
   • Past high-dose radiation for other illnesses.
5. Genetic Factors
   • A changed BAP1 gene raises the risk (Testa et al., 2011).

Note: Smoking by itself does not directly cause mesothelioma, but it can worsen other lung problems when combined with asbestos (ACS, 2023b).

Signs and Symptoms (Clinical Presentation)

Because mesothelioma takes a long time to develop, people might not notice symptoms until the disease is advanced. Different sites have different typical symptoms:

Pleural Mesothelioma (Most Common)

• Shortness of Breath: Often caused by fluid buildup (effusion) around the lungs.
• Chest Pain: Usually in the lower chest or along the ribs.
• Long-Lasting Cough: Usually dry.
• Feeling Tired or Weak.

Peritoneal Mesothelioma

• Swollen Abdomen: Due to fluid called ascites.
• Abdominal Pain: Can be mild or severe.
• Bowel Changes: Constipation or diarrhea.
• Weight Loss: Often in more advanced disease.

Rare Forms

• Pericardial Mesothelioma: May present with chest pain, palpitations, or fluid around the heart.
• Tunica Vaginalis Mesothelioma: Can show up as swelling or a lump in the testicle area.

These signs can be confused with more common conditions such as pneumonia or irritable bowel syndrome. Doctors should consider the risk of mesothelioma if a patient has a significant asbestos exposure history and unexplained symptoms (Kindler, 2013).

How Doctors Diagnose It

Diagnosing mesothelioma is difficult because it can look like other diseases. Doctors use a variety of steps (Husain et al., 2018):

1. Medical History and Physical Exam
   • Checking for jobs or places tied to asbestos.
   • Looking for signs like chest pain, breathing issues, or abdominal swelling.
2. Imaging Tests
   • Chest X-ray: May show thickening or fluid around the lungs.
   • CT Scan (Computed Tomography): Gives a clearer view of the pleura or peritoneum.
   • MRI (Magnetic Resonance Imaging): Useful for seeing if the tumor has spread into muscles or other structures.
   • PET Scan (Positron Emission Tomography): Shows active tumor sites based on how cells use glucose (NCI, 2022).
3. Tissue Biopsy
   • Needle Biopsy: Often guided by imaging to sample suspicious tissue.
   • Thoracoscopy or Laparoscopy: Surgeons use a thin camera to see the pleura or peritoneum and take tissue samples.
   • Immunohistochemistry (IHC): Special lab tests on the tissue that detect markers (like calretinin, WT1, and certain cytokeratins) to confirm mesothelioma and not another type of cancer (Husain et al., 2018).
4. Biomarkers
   • Researchers are studying blood markers such as mesothelin or fibulin-3, but these are not perfect tests (Pass et al., 2014).
   • New techniques look for circulating tumor DNA (ctDNA) or microRNAs.

An accurate diagnosis is critical because it affects both treatment choices and the patient’s outlook.

Staging the Disease

After a diagnosis, doctors “stage” the disease to see how far it has spread. For pleural mesothelioma, many use the TNM system (Tumor, Node, Metastasis) from the American Joint Committee on Cancer (AJCC):

• Stage I: Tumor is only on one side of the pleura. No or minimal lymph node involvement.
• Stage II: Tumor may be larger, possibly in the lung or diaphragm, and may have some lymph node involvement.
• Stage III: Tumor is advanced and may have spread more deeply into the chest wall or multiple lymph nodes.
• Stage IV: Disease has spread to distant areas, or is too extensive to remove (Kindler, 2013).

For peritoneal mesothelioma, doctors often use the Peritoneal Cancer Index (PCI), which measures how much tumor is present in different parts of the abdomen (NCI, 2022). Staging helps doctors decide whether the tumor can be removed by surgery and what other treatments might be needed.

Treatment Options

Surgery

• Extrapleural Pneumonectomy (EPP): The surgeon removes the affected lung, part of the diaphragm, the pleura, and sometimes part of the pericardium. It is a major operation, usually for patients with earlier-stage disease who are strong enough to handle it (Sugarbaker et al., 2018).
• Pleurectomy/Decortication (P/D): Removes the lining around the lung and any visible tumors but leaves the lung itself. This may help with breathing and ease symptoms.
• Cytoreductive Surgery (CRS) for Peritoneal Mesothelioma: Removes as much tumor as possible in the abdomen. Afterward, doctors may apply heated chemotherapy (HIPEC) directly in the abdominal cavity to kill leftover cancer cells (Votanopoulos et al., 2018).

Chemotherapy

• Standard Treatment: A combination of cisplatin and pemetrexed is the main first-line therapy for patients whose disease cannot be removed or who are not surgery candidates (Kindler, 2013). If cisplatin is too toxic, doctors may use carboplatin.
• Combination Therapy: Chemotherapy may be used before surgery (neoadjuvant) or after surgery (adjuvant) to reduce tumor size or destroy leftover cells.

Radiation Therapy

• Adjuvant Radiation: Given after surgery to destroy tiny cancer spots that remain.
• Palliative Radiation: Helps control pain or other symptoms in more advanced disease, even if it does not cure the cancer.

Immunotherapy and Targeted Drugs

• Immune Checkpoint Inhibitors: Drugs like nivolumab or ipilimumab can boost the immune system to attack the cancer. Some trials have shown longer survival in certain patients (Baas et al., 2021).
• Targeted Therapies: Researchers are studying treatments that block specific molecules (like VEGF or EGFR) in tumor cells. Results vary, but studies continue.

Palliative Care

Since mesothelioma is often advanced at diagnosis, palliative care plays a big role. This care aims to improve quality of life by managing pain, breathlessness, or fluid buildup. Procedures like pleurodesis (fusing the pleura to prevent fluid collection) or placing a drain can help ease symptoms (Kindler, 2013). Emotional and social support for patients and families is also key.

Outlook (Prognosis)

Mesothelioma usually has a poor prognosis, partly because it is often detected late (NCI, 2022). However, each patient’s outlook depends on several factors:

• Stage: Early-stage disease that can be surgically removed may offer better survival than advanced disease.
• Cell Type (Histology): Epithelioid tumors often respond better to treatment compared to sarcomatoid or biphasic tumors.
• Patient Health: A person’s overall health and ability to handle surgery or strong chemotherapy matter a lot.
• Treatment Approach: Combination treatments (surgery, chemo, and possibly radiation or immunotherapy) can lengthen survival for some patients (Steliga & Yokoi, 2021).

Researchers are working hard to find better ways to detect and treat mesothelioma earlier, which may improve survival in the future.

Prevention and Public Health

Preventing mesothelioma depends on reducing asbestos exposure (CDC, 2020). Many countries have strict rules or full bans on asbestos use, but not all. People can still find asbestos in old buildings or certain products.

Key Prevention Efforts

1. Workplace Safety
   • Setting limits on asbestos exposure.
   • Providing protective equipment for workers in at-risk jobs.
2. Removing Asbestos
   • Properly handling and disposing of old materials containing asbestos.
   • Cleaning up areas near old mines or factories.
3. Public Awareness
   • Teaching people about the dangers of asbestos.
   • Advising homeowners or builders to hire certified professionals for asbestos inspections.
4. Monitoring Exposed Groups
   • Keeping track of people who worked in high-risk jobs.
   • Checking for early signs of disease, though we do not yet have a perfect screening test.

Mesothelioma creates big medical costs and legal claims against companies that used asbestos. Governments and health agencies keep trying to remove asbestos from markets and protect workers, but the process is not the same in all countries (Odgerel et al., 2017).

Ongoing Research

Biomarkers

Scientists are searching for blood or tissue markers that might help find mesothelioma earlier. Tests for mesothelin, fibulin-3, or circulating tumor DNA could help doctors screen people who were exposed to asbestos, so they can get treatment sooner (Pass et al., 2014).

Personalizing Treatment

Better genetic profiling of tumors could help match treatments to each patient’s cancer. For example, if a patient’s mesothelioma has a damaged BAP1 gene, new drugs might target that pathway (Testa et al., 2011).

Advanced Immunotherapy

Trials look at combinations of immune drugs, as well as CAR T-cell therapy (cells designed in the lab to attack cancer). Researchers hope that combining these with surgery or chemotherapy can further improve survival (Baas et al., 2021).

Improved Surgical Techniques

Refinements in minimally invasive procedures and robotic surgeries may offer safer ways to remove tumors and reduce problems after surgery (Sugarbaker et al., 2018). Imaging improvements could help surgeons see small tumors and remove them more completely.

Policy and Advocacy

Groups like the World Health Organization (WHO) push for a worldwide asbestos ban (WHO, 2014). They also call for better compensation for victims and more public health measures to prevent exposure. Activists and researchers want stronger rules to protect workers and citizens from asbestos dust.

Conclusion

Mesothelioma is a severe cancer that most often arises from long-term asbestos exposure. It remains a major concern in public health and occupational safety because of its late onset and poor survival rates. Even though many nations have cut back on or banned asbestos, the disease continues to appear due to its long latency.

On the brighter side, surgery, chemotherapy, immunotherapy, and combined treatments have helped some patients live longer than ever before. Researchers are also exploring new biomarkers and therapies that may lead to earlier diagnosis and better results.

For now, the best way to reduce mesothelioma cases is to prevent asbestos exposure, whether at work or at home. By removing or containing asbestos in older buildings, enforcing strict workplace rules, and educating the public, we can limit future harm. Through combined efforts in medicine, policy, and research, the hope is to greatly lower the burden of this disease.

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