What is mesothelioma?

What is Mesothelioma?

Mesothelioma is a rare, aggressive cancer arising from mesothelial cells that line body cavities, most commonly the pleural lining of the lungs (malignant pleural mesothelioma), and is directly attributable to asbestos exposure in approximately 80-85% of cases. 1, 2

Disease Classification and Sites

Mesothelioma can develop in several anatomical locations:

• Pleural mesothelioma (most common): affects the lining of the lungs and accounts for approximately 70% of all mesotheliomas 1, 3
• Peritoneal mesothelioma: affects the abdominal lining and represents about 30% of cases 4
• Pericardial and tunica vaginalis mesothelioma: rare variants affecting the heart lining and testicular lining, respectively 3, 4

Etiology and Pathophysiology

The World Health Organization classifies malignant pleural mesothelioma as directly attributable to all types of asbestos exposure, making it both an industrial and preventable disease. 1

• Asbestos exposure accounts for more than 80-85% of cases, with occupational exposure being the primary route 1, 2
• The disease has an extremely long latency period of 20-50 years between initial asbestos exposure and clinical presentation 1, 2
• Asbestos fibers persist in tissue, causing chronic inflammation that leads to DNA damage and eventual malignant transformation 3
• Germline mutations in the BAP1 gene have been linked to predisposition in some cases, and somatic mutations in tumor suppressor genes (BAP1, CDKN2A, CDKN2B, MTAP, NF2, TP53) characterize the genomic landscape 1, 3

Epidemiology and Incidence

Mesothelioma is a disease of the elderly, being rare below age 50 years, with a median age at diagnosis of 72-76 years. 1, 2

• Incidence is significantly higher in males than females, with world-standardized rates per 100,000 persons of 1.7 versus 0.4 in Europe and 0.7 versus 0.3 in the United States 1
• Approximately 2,500 new cases occur annually in the United States 2
• Incidence is highest in countries with greatest previous asbestos use such as the Netherlands, UK, and Australia 1
• Despite asbestos bans in 67 countries, incidence continues to rise in many regions due to the long latency period, and asbestos use continues to increase in the developing world 1

Clinical Presentation

Patients typically present with:

• Dyspnea (shortness of breath), chest pain, and weight loss as the primary symptom triad 1
• Symptoms occurring over many months before diagnosis 1
• Unilateral pleural effusions on physical examination 1
• For peritoneal mesothelioma: ascites, abdominal pain, asthenia, weight loss, anorexia, abdominal mass 4

A detailed occupational history is critical for both diagnosis and potential legal compensation. 1

Histological Subtypes

Mesotheliomas are classified into three distinct subtypes based on histology:

• Epithelioid subtype: most common with the best prognosis 3
• Biphasic subtype: intermediate prognosis 3
• Sarcomatoid subtype: worst prognosis 3

Prognosis

Mesothelioma carries a dismal prognosis with median overall survival of approximately 9.5-12 months, with cure being rare. 2, 5

• One-year survival rate: 41% 2
• Three-year survival rate: 12% 2
• Histological subtype and patient performance status are the most important prognostic factors 2
• The disease substantially affects quality of life in physical and emotional domains, impacting both patients and their families 3