Mesothelioma

Essentials of Diagnosis

• Unilateral, nonpleuritic chest pain and dyspnea

• Pleural effusion or pleural thickening or both on chest radiographs

• Mesothelial cells in pleural fluid or tissue

• Commonly, a distant (> 20 years earlier) history of exposure to asbestos

General Considerations

• Primary tumors arising from the mesothelial surfaces of the pleura (80% of cases) or peritoneum (20% of cases)

• Mesothelioma is almost always malignant (especially, pleural location), with malignant cells on histology; rarely, mesothelioma is benign (usually, abdominal location) with cystic, adenomatoid, fibrous changes on histology

• 75% of pleural mesotheliomas are diffuse (usually malignant)

• The average interval between onset of symptoms and diagnosis is 2–3 months, with median age at diagnosis of 72 to 74 years in Western countries

• The latent period between asbestos exposure and onset of symptoms ranges from 20 to 40 years

Demographics

• Men outnumber women 3:1

• Malignant pleural mesothelioma is associated with asbestos exposure (60–80% of cases); the lifetime risk to asbestos workers is 10%

• Cigarette smoking significantly increases the risk of bronchogenic carcinoma in asbestos workers and aggravates asbestosis, but there is no association between smoking and mesothelioma independent of the asbestos exposure

• Asbestos exposure occurs from work in

  • Mining

  • Milling

  • Manufacturing

  • Shipyard work

  • Insulation

  • Brake linings

  • Building construction and demolition

  • Roofing materials

  • Other asbestos-containing products (eg, some "popcorn" ceilings)

Symptoms and Signs

• Insidious onset of shortness of breath, nonpleuritic chest pain, and weight loss

• Physical findings include

  • Dullness to percussion

  • Diminished breath sounds

  • Clubbing of fingers (some cases)

• Malignant pleural mesothelioma progresses rapidly as the tumor spreads along the pleural surface to involve the pericardium, mediastinum, and contralateral pleura

• Tumor may eventually extend beyond the thorax to involve abdominal lymph nodes and organs

Differential Diagnosis

• Chronic organized empyema

• Sarcoma

• Metastatic cancer to the pleura, especially adenocarcinoma

• Malignant fibrosing histiocytoma

• Other causes of pleural effusion (see Pleural Effusion)

Laboratory Tests

• Pleural fluid analysis often reveals a hemorrhagic exudate

• Cytologic tests of pleural fluid are often negative

• Soluble mesothelin-related peptide and fibulin-3 may be found in serum or pleural fluid (or both) of patients with malignant mesothelioma

Imaging Studies

• Radiographic findings

  • Nodular, irregular, unilateral pleural thickening

  • Varying degrees of unilateral pleural effusion

• CT helps determine the extent of pleural involvement

• PET-CT helps differentiate benign from malignant pleural disease, improve staging accuracy, and identify candidates for aggressive surgical approaches

Diagnostic Procedures

• Thoracentesis

• Video-assisted thoracoscopic surgery (VATS) biopsy is usually necessary to obtain an adequate specimen for histologic diagnosis; special stains and electron microscopy may be needed to confirm the diagnosis

Medications

• Chemotherapy: pemetrexed and cisplatin; bevacizumab and pemetrexed; others

• For advanced unresectable disease,

  • Palliative chemotherapy with pemetrexed and cisplatin can achieve response rates of 30–40%, extend median overall survival to 12 months, and improve quality of life

  • Adding bevacizumab (a monoclonal antibody to vascular endothelial growth factor [VEGF]) to cisplatin and pemetrexed has been shown to further improve overall survival

  • For patients with comorbidities who may suffer increased toxicity, carboplatin can be substituted for the cisplatin

  • For patients whose disease progresses on first-line treatment, second-line regimens include

    • Chemotherapy with gemcitabine, anthracyclines, or vinorelbine

    • Immunotherapy, with either nivolumab plus ipilumumab or pembrolizumab alone

Surgery

• For localized disease, options include

  • Pleurectomy and decortication (surgical stripping of the pleura and pericardium from apex of the lung to diaphragm)

  • Extrapleural pneumonectomy (EPP) (a radical surgical procedure involving removal of the ipsilateral lung, parietal and visceral pleura, pericardium, and most of the hemi-diaphragm)

• Surgical cytoreduction alone is not sufficient, and either chemotherapy or radiation therapy (or both) should be included in a multimodality approach

• However, the results of the Mesothelioma and Radical Surgery (MARS) trial showed that EPP offers no survival benefit and may cause more harm than good

Therapeutic Procedures

• Drainage of effusions, pleurodesis, radiation therapy, and surgical resection may offer palliative benefit

Complications

• Local invasion of thoracic structures with superior vena cava syndrome, hoarseness, Horner syndrome, dysphagia, arrhythmias

• Paraneoplastic syndrome

  • Thrombocytosis

  • Hemolytic anemia

  • Disseminated intravascular coagulation

  • Migratory thrombophlebitis

• Metastatic disease

Prevention

• Avoidance of tobacco smoke (primary or secondary) in those with a history of asbestos exposure

Prognosis

• Median survival from symptom onset ranges from 7 months in extensive disease to 17 months in localized disease

• Most patients die of respiratory failure and complications of local extension

• 5-year survival rate is 5–10%

When to Refer

• Upon diagnosis, refer to a pulmonologist, oncologist, or possibly a thoracic surgeon who can evaluate the patient for multidisciplinary treatment

When to Admit

• For pleural fluid drainage (thoracenteses, placement of an indwelling drainage catheter)

• For severe dyspnea

• For pain management