What is mesothelioma?

Mesothelioma: Definition, Diagnosis, and Management

Mesothelioma is a rare, aggressive cancer that primarily affects the pleural lining of the lungs, strongly associated with asbestos exposure and characterized by a long latency period of 20-40 years after initial exposure. 1

Definition and Epidemiology

• Malignant pleural mesothelioma (MPM) is the most common form, arising from mesothelial cells that line the pleural cavity, though mesothelioma can also occur in the peritoneum, pericardium, and tunica vaginalis testis 1, 2
• Approximately 2,500 new cases occur annually in the United States, with incidence rates still increasing in many countries despite asbestos bans 1
• The disease predominantly affects older men (median age 72-76 years) with a history of asbestos exposure, which accounts for approximately 85% of cases 1
• Median overall survival is approximately 1 year, with cure being rare 1

Pathology and Classification

• Three main histological subtypes exist: epithelioid (most common with better prognosis), sarcomatoid (worst prognosis), and biphasic (mixed) 1
• The WHO 2004 classification is recommended for diagnosis and management of mesothelial tumors 1
• Molecular characteristics include frequent alterations in tumor suppressor genes, particularly BAP1, CDKN2A, CDKN2B, MTAP, NF2, and TP53 2, 3

Clinical Presentation

• Common symptoms include dyspnea, chest pain, pleural effusion, fatigue, cough, weight loss, and loss of appetite 1
• Clinical manifestations are typically nonspecific and insidious, even in cases with previous asbestos exposure 1
• The disease has a high symptom burden, significantly impacting quality of life 1

Diagnostic Approach

Imaging

• Chest radiographs typically show unilateral pleural effusion or thickening but are insufficient for definitive diagnosis 1
• Chest CT scan is essential, with diffuse or nodular pleural thickening being suggestive of MPM 1
• MRI and PET scanning are not currently considered primary diagnostic tools for mesothelioma 1

Biopsy and Pathological Diagnosis

• Thoracoscopy is strongly recommended as the preferred method for obtaining diagnostic tissue samples, except in cases with contraindications or pleural symphysis 1
• Diagnosis must always be based on immunohistochemical examination in addition to morphological assessment 1
• For epithelioid mesothelioma, two positive mesothelioma markers (such as calretinin, Wilms tumor antigen-1, or epithelial membrane antigen) should be used to differentiate from adenocarcinoma 1
• Cytological examination of pleural fluid alone is often insufficient for definitive diagnosis 1

Management Approach

Multidisciplinary Care

• Patients should be managed by a multidisciplinary team with experience in MPM 1
• Initial evaluation should include CT chest with contrast, thoracentesis for cytologic assessment, and pleural biopsy 1

Pleural Effusion Management

• For symptomatic pleural effusions, either talc pleurodesis (via slurry or poudrage) or indwelling pleural catheters should be offered based on patient preference 1
• Talc pleurodesis is preferred over video-assisted thoracoscopic surgery partial pleurectomy (VATS-PP) for fluid control 1

Systemic Therapy

• First-line therapy for patients with good performance status (WHO 0-1) should be cisplatin and pemetrexed 1
• Where licensed, bevacizumab should be added to cisplatin and pemetrexed 1
• Carboplatin can be substituted for cisplatin when contraindicated 1
• Pemetrexed or vorinostat should not be offered as second-line treatment 1
• Clinical trials are recommended for second-line treatment in patients with adequate performance status 1

Surgical Options

• Surgical options include pleurectomy/decortication (P/D) with mediastinal lymph node sampling or extrapleural pneumonectomy (EPP) 1
• EPP is not recommended for patients with sarcomatoid histology due to higher morbidity 1
• The goal of surgery is complete gross cytoreduction of the tumor 1
• For patients with early disease (confined to pleural envelope, no N2 lymph node involvement) and epithelioid histology, EPP may be the best option 1

Supportive Care

• Palliative care is crucial for symptom management 1
• Palliative radiotherapy should be considered for chest pain, bronchial or esophageal obstruction, or other symptomatic sites 1
• Follow-up appointments with an oncologist, respiratory physician, or specialist nurse should be offered every 3-4 months 1

Prognosis and Monitoring

• Histological subtype and patient performance status are the most important prognostic factors 1
• Median survival is approximately 9.5 months, with 1-year and 3-year survival rates of 41% and 12%, respectively 1
• Regular monitoring should include assessment of disease response and quality of life 1

Mesothelioma remains a challenging disease with limited treatment options and poor outcomes. Early diagnosis through thoracoscopic biopsy with immunohistochemical confirmation is essential, followed by a multidisciplinary approach to treatment that may include chemotherapy, surgery in select cases, and comprehensive supportive care.