Mesothelioma: Symptoms, Types, Causes and Treatment

Mesothelioma is a rare but aggressive cancer that originates in the mesothelial cells lining the body’s internal organs, most commonly the lungs (pleura) and abdomen (peritoneum). Known for its strong association with asbestos exposure, mesothelioma is challenging to diagnose and treat, often presenting late with a high symptom burden and limited prognosis. As global incidence continues to rise in some regions, a comprehensive understanding of its symptoms, types, causes, and treatment options is critical for patients, families, and healthcare professionals alike.

Symptoms of Mesothelioma

Mesothelioma’s symptoms can be insidious, often mimicking more common conditions, which unfortunately leads to delayed diagnosis. Both physical and emotional symptoms significantly impact quality of life, with patients frequently experiencing a complex array of issues that evolve as the disease progresses.

Symptom	Description	Frequency/Severity	Source(s)
Pain	Persistent chest/abdominal pain	Very common, often severe	1, 2, 4
Breathlessness	Shortness of breath (dyspnea)	Very common	1, 2, 3, 4
Fatigue	Persistent tiredness/weakness	Frequent	1, 2, 4
Cough	Dry or productive cough	Common	1, 4, 5
Appetite loss	Reduced hunger/weight loss	Common	1, 2, 3
Sweating	Night sweats or general sweating	Reported	1, 5
Emotional	Anxiety, depression, isolation	Significant impact	1
Other	Pleural effusion, sleep disturbance	Often present	2, 5

Table 1: Key Symptoms of Mesothelioma

Physical Symptoms

Mesothelioma’s physical symptoms are typically driven by tumor growth and the body’s response to it. The most common symptoms include:

• Pain: Usually chest pain for pleural mesothelioma, or abdominal pain in peritoneal cases. Pain is often persistent, and can be severe despite high doses of analgesics 1, 2.
• Breathlessness: As tumors grow, they can cause pleural effusions (fluid build-up around the lungs), making breathing difficult and sometimes requiring repeated fluid drainage 3, 5.
• Fatigue and Weakness: Cancer-related fatigue is widespread, affecting daily activities and quality of life 1, 2, 4.
• Cough and Pleural Effusion: Chronic cough and recurring fluid build-up are common, especially in pleural mesothelioma 4, 5.
• Poor Appetite and Weight Loss: These are hallmark symptoms in many advanced cancers, including mesothelioma, often leading to significant weight loss 1, 3.

Emotional and Social Impact

Mesothelioma’s impact goes beyond physical discomfort:

• Anxiety and Depression: The diagnosis, prognosis, and symptom burden cause significant emotional distress, often resulting in anxiety, depression, fear, and isolation 1.
• Social Consequences: Changes in family roles, relationships, and social interactions are common as the disease progresses 1.

Symptom Trajectory and Burden

• Symptoms often worsen as the disease advances.
• Many patients are referred to palliative care late, despite having high symptom burden; earlier integration of supportive care could improve quality of life 2.
• High symptom scores (using tools like the MD Anderson Symptom Inventory) correlate with declining well-being and function 4.

Types of Mesothelioma

Mesothelioma is not a single disease, but a group of related cancers that vary by location, cell type, and behavior. Understanding these distinctions is vital for diagnosis and treatment planning.

Type	Site/Cell Subtype	Features/Prognosis	Source(s)
Pleural	Lungs (pleura)	Most common (85%), poor prognosis	3, 10
Peritoneal	Abdomen (peritoneum)	Second most common; better prognosis with treatment advances	5, 19
Pericardial	Heart (pericardium)	Very rare, difficult to treat	5, 11
Epithelioid	Cell subtype	Most common, best prognosis	7, 8, 9
Sarcomatoid	Cell subtype	More aggressive, worst prognosis	7, 8, 9
Biphasic	Mixed cell subtype	Features of both above; intermediate prognosis	7, 8, 9

Table 2: Main Types and Subtypes of Mesothelioma

By Location

• Pleural Mesothelioma:

  • Arises from the pleural lining of the lungs.
  • Accounts for approximately 85% of cases.
  • Most often linked to asbestos exposure 3, 10.
  • Symptoms include chest pain, breathlessness, persistent cough, and pleural effusion 1, 3.

• Peritoneal Mesothelioma:

  • Originates in the lining of the abdomen.
  • Far less common than pleural type.
  • Presents with abdominal pain, swelling, and digestive issues 5, 19.
  • Prognosis has improved with new treatments.

• Pericardial Mesothelioma:

  • Occurs in the heart’s lining.
  • Extremely rare and difficult to treat due to location 5, 11.

By Cell (Histological) Subtype

• Epithelioid:

  • The most common histological variant.
  • Cells resemble normal mesothelial cells.
  • Responds better to treatment and has the best prognosis among subtypes 7, 8, 9.

• Sarcomatoid:

  • Less common, more aggressive.
  • Cells are spindle-shaped and resemble sarcoma.
  • Poor response to treatment and the worst prognosis 7, 8, 9.

• Biphasic (Mixed):

  • Contains both epithelioid and sarcomatoid features.
  • Prognosis and behavior are intermediate 7, 8, 9.

Diagnostic Challenges and Subtypes

• Recent advances in pathology and molecular markers (e.g., BAP1 loss) have improved diagnostic accuracy, which is critical for access to appropriate compensation and care 8, 19.
• The classification and grading of mesothelioma subtypes are important for prognosis and treatment decisions 8.

Causes of Mesothelioma

The root causes of mesothelioma are both environmental and genetic, with asbestos exposure as the principal culprit. However, not all cases are linked to asbestos, and other factors can play a significant role.

Cause	Mechanism/Description	Relative Importance	Source(s)
Asbestos	Inhaled/ingested fibers cause inflammation, DNA damage	Major cause (~80% of cases)	3, 11, 13, 14, 15
Other Mineral Fibers	Erionite, fluoro-edenite, balangeroite	Significant in certain regions	11, 12, 14, 15
Radiation	Previous therapeutic radiation	Established, but rare	12, 13, 15
Genetic Factors	BAP1 mutations, family clusters	Small proportion, but rising recognition	6, 12, 13, 14, 15, 19
Viruses	Simian Virus 40 (SV40)	Possible co-carcinogen	13, 14, 15
Other	Spontaneous (idiopathic), chronic inflammation	Minority of cases	12, 14

Table 3: Causes and Risk Factors for Mesothelioma

Asbestos Exposure

• Primary Risk Factor: Exposure to asbestos fibers, particularly in occupational settings such as construction, shipbuilding, and insulation manufacturing, is the leading cause of mesothelioma 3, 11, 13.
• No Safe Level: There is no known safe threshold for asbestos exposure 3.
• Latency: Disease typically appears decades (20–50 years) after exposure, complicating prevention and early detection 3, 14.

Other Mineral Fibers

• Erionite: A naturally occurring mineral fiber, highly carcinogenic, responsible for regional epidemics (e.g., Cappadocia, Turkey) 11, 14, 15.
• Other Fibers: Fluoro-edenite, balangeroite, and possibly carbon nanotubes (in animal studies) may also contribute 12.

Radiation and Other Environmental Factors

• Radiation: Previous therapeutic radiation (e.g., for lymphoma) is an established but rare cause 12, 13, 15.
• Chronic Inflammation: Long-term pleural inflammation might increase risk, but data are limited 12.

Genetic Predisposition

• BAP1 Mutations: Germline mutations in the BAP1 gene can predispose individuals to mesothelioma and other cancers (BAP1 cancer syndrome) 6, 12, 14, 19.
• Family Clusters: Certain families and regions show higher rates due to genetic susceptibility 13, 14, 15.
• Interaction with Environment: Genetics may explain why only a fraction of those exposed to asbestos develop the disease 14, 15.

Viral and Other Factors

• SV40 Virus: Simian Virus 40 has been linked to mesothelioma in animal studies and may act as a co-carcinogen with asbestos in humans, though its role in people remains controversial 13, 14, 15.
• Idiopathic Cases: Some cases have no identifiable cause ("spontaneous") 12.

Treatment of Mesothelioma

While there is currently no cure for mesothelioma, recent advances are offering new hope. Treatment is complex and tailored to each patient, often requiring a multidisciplinary approach and a balance between extending survival and preserving quality of life.

Treatment	Description/Approach	Outcomes/Notes	Source(s)
Chemotherapy	Pemetrexed + cisplatin/carboplatin (+/- bevacizumab)	Standard of care, improves survival	16, 17, 18
Surgery	Extrapleural pneumonectomy, pleurectomy/decortication	Selected cases, controversial benefit	17, 19
Radiation Therapy	Curative/adjuvant, palliative	Used for symptom control, limited survival impact	17, 20
Immunotherapy	Checkpoint inhibitors (e.g., anti-PD-1/PD-L1)	Emerging, especially for sarcomatoid subtype	6, 17, 19
Palliative Care	Symptom relief, quality of life focus	Essential throughout disease course	1, 2, 17
Multimodality	Combination of above	May offer best outcomes in selected patients	17, 18, 19

Table 4: Main Treatment Approaches in Mesothelioma

Chemotherapy

• Pemetrexed plus Cisplatin/Carboplatin: The backbone of systemic therapy; shown to improve survival and quality of life 16, 17, 18.
• Bevacizumab (Avastin): Adding this anti-angiogenic agent to standard chemotherapy further increases overall survival at the cost of manageable side effects 16.
• Second-line Options: Retreatments with platinum agents or other drugs like gemcitabine are sometimes used, with modest benefit 18.

Surgery

• Types: Extrapleural pneumonectomy (removal of lung and pleura) and pleurectomy/decortication (removal of diseased pleura, sparing the lung) 17, 19.
• Role: Surgery is controversial; it may benefit a select group of patients with early-stage disease, good health, and favorable tumor subtype 17, 19.
• Peritoneal Mesothelioma: Cytoreductive surgery plus heated intraperitoneal chemotherapy (HIPEC) has improved outcomes for abdominal cases 19.

Radiation Therapy

• Purpose: Used for symptom control (pain, obstruction), prevention of tumor seeding, and as adjunct to surgery 17, 20.
• Techniques: Includes conventional and advanced methods like proton beam therapy 20.
• Limitations: Limited by toxicity to surrounding organs; not curative alone 20.

Immunotherapy and Targeted Therapy

• Checkpoint Inhibitors: Drugs targeting PD-1 or PD-L1 pathways are showing promise, particularly in sarcomatoid and high PD-L1 expression subtypes 6, 17, 19.
• Personalized Therapy: Advances in genomic profiling (e.g., BAP1, NF2 mutations) may soon allow more targeted treatment approaches 6, 19.

Palliative and Supportive Care

• Symptom Management: Critical throughout the disease, not just at end-of-life 1, 2, 17.
• Interventions: Include pain control, drainage of pleural effusions, respiratory support, and emotional/psychosocial care 1, 2.
• Early Integration: Improves patient comfort and can be started at diagnosis 2.

Multimodality Treatment

• Combined Approach: Surgery, chemotherapy, and radiation may be combined for eligible patients, offering potential survival benefit 17, 18, 19.
• Individualization: Treatment plans must be tailored, considering tumor subtype, patient health, preferences, and genetic factors.

Conclusion

Mesothelioma remains a formidable cancer with a complex interplay of causes, diverse clinical presentations, and challenging treatment decisions. Understanding its symptoms, types, risk factors, and available therapies is crucial for patients and clinicians navigating this diagnosis.

Key Takeaways:

• Symptoms: Mesothelioma often presents with pain, breathlessness, fatigue, and significant emotional and social impacts, with symptoms worsening as the disease advances 1, 2, 3, 4.
• Types: Pleural mesothelioma is most common; subtypes (epithelioid, sarcomatoid, biphasic) have distinct prognoses and influence treatment 3, 7, 8, 9.
• Causes: Asbestos is the predominant cause, but other mineral fibers, radiation, genetics, and possibly viruses also play roles 3, 11, 12, 13, 14, 15.
• Treatment: No cure exists, but chemotherapy, surgery, radiation, immunotherapy, and palliative care—often in combination—can extend life and improve quality of life for many patients 16, 17, 18, 19, 20.

As research continues to uncover new insights into the biology and optimal management of mesothelioma, multidisciplinary and individualized care remains essential to improving outcomes for those affected by this challenging disease.