Diseases of the Pleura and Mediastinum
Summary of Key Points
Malignant Pleural Mesothelioma (MPM)
Epidemiology
• MPM is a rare disease with 2,000 to 3,000 cases annually in the United States.
• It is associated with prior occupational asbestos exposure, but some patients without known asbestos exposure will develop MPM.
• Four subtypes exist: epithelioid, sarcomatous, biphasic epithelial (also referred to as mixed), and desmoplastic.
• Epithelioid is the most common and may be associated with a better prognosis.
Differential Diagnosis
• Diagnosis must be differentiated from metastatic adenocarcinoma or non–small cell lung cancer with adenocarcinoma histology. No single test is diagnostic of MPM, and it frequently requires a panel of immunohistochemistry markers to confirm the diagnosis.
• Cytologic analysis of pleural fluid is not reliable to exclude MPM, and many times a thoracoscopic biopsy may be required for definitive diagnosis. Evidence of invasion into subpleural adipose tissue is the most reliable indicator of malignancy.
Staging
• Computed tomographic (CT) scan is the initial staging procedure.
• Positron emission tomography (PET) or PET-CT scan has the ability to detect extrathoracic disease.
• Cervical mediastinoscopy may be useful for detecting mediastinal involvement.
• Peritoneal lavage or laparoscopy is indicated if peritoneal involvement is suspected.
Primary Therapy
• For patients with operable disease without significant co-morbidities, surgical options include extrapleural pneumonectomy or pleurectomy and decortication.
• Single-institution and phase II trials have demonstrated the feasibility of multimodality therapy.
• The benefit of post- or preoperative radiation and chemotherapy is undefined.
• For patients with unresectable disease or metastatic disease, without significant treatment co-morbidities, and preserved performance status, treatment with a platinum agent (cisplatin or carboplatin) and antifolate (pemetrexed or raltitrexed) is the standard therapy.
• A variety of agents have shown activity in the second-line setting.
• Radiation therapy provides palliation of symptoms, and postoperative radiation therapy may reduce the rate of local and port site recurrence.
Thymoma
• Most common of all mediastinal tumors, it comprises approximately 20% of the tumors of the mediastinum.
• Differential includes thymoma, thymic carcinoma, and thymic carcinoid.
• Approximately 50% of patients with thymoma are asymptomatic at the time of diagnosis.
• Thymomas may be associated with parathymic syndromes (e.g., myasthenia gravis, pure red blood cell aplasia, and hypogammaglobulinemia)
• Thymomas are classified according to the World Health Organization (WHO) classification, which is associated with 10-year overall survival rates.
• Primary therapy is complete surgical resection.
• Postoperative radiation therapy should be considered for patients with stage IIB disease, close surgical margins, WHO grade B type, and tumor adherent to the pericardium.
• Chemotherapy with cisplatin or anthracycline-based therapy is an option for patients with unresectable or metastatic disease.
Malignant Pleural Effusions
• Patients with malignant pleural effusions have a poor prognosis, and pleural effusion is considered metastatic disease.
• Common symptoms include dyspnea on exertion, shortness of breath, and cough.
• Most common causes of malignant pleural effusion are lung cancer, breast cancer, lymphoma, and cancer of unknown primary.
• Cytology can be diagnostic of type of malignancy, and patients with exudative effusion and known metastatic cancer should be considered as having a malignant pleural effusion.
• Thoracentesis may be diagnostic and provide symptomatic relief for the patient.
• Management strategies include intermittent thoracentesis, indwelling pleural catheters, and talc pleurodesis. The optimal treatment strategy may depend on the patient’s prognosis, performance status, and type of malignancy.
1. For patients with MPM in the differential diagnosis which of the following statements are correct?
A For a patient with suspected MPM, a cytologic review of pleural effusion effectively eliminates MPM from the differential diagnosis.
B The absence of asbestos exposure eliminates MPM from the differential diagnosis.
C Evidence of invasion into subpleural adipose tissue the most reliable indicator of malignancy.
D A single immunohistochemistry test can effectively determine a malignant cell is MPM, non–small cell lung cancer with adenocarcinoma histology, or metastatic adenocarcinoma.
2. For patients who have undergone complete resection of thymoma, postoperative radiation therapy should be considered for all the following patients except
3. For patients with potentially resectable MPM, which of the following are relevant preoperative factors for extrapleural pneumonectomy?
1. Answer: C. Thoracentesis is frequently the initial procedure performed in patients with pleural effusions or suspected MPM. However, cytologic evaluation of pleural effusion is unreliable and diagnostic cytologic criteria have not been established. Evidence of invasion of the subpleural adipose tissue is the most reliable marker of malignancy. A single stain of immunohistochemistry (IHC) test is not diagnostic of MPM, and many centers use a panel of IHC tests that are positive in MPM and negative in MPM to arrive at a pathological diagnosis.
2. Answer: D. Although definitive randomized trials have not been performed, current recommendations support postoperative radiation for resected stage I thymomas because of the low recurrence rates. For patients with close surgical margins or tumor adherent to the pericardium, WHO grade B, or stage IIB disease, postoperative radiation therapy should be considered, including the potential long-term toxicities.
3. Answer: E. Patients with underlying co-morbidities or limited pulmonary reserve are not considered candidates for extrapleural pneumonectomy. Thus, postoperative FEV1, room air Pco2 and Po2, and an assessment of underlying co-morbidities are essential in the selection of patients for extrapleural pneumonectomy. Patients with malignant involvement in the mediastinal lymph nodes have a worse prognosis than patients with no involvement, and this can be used as a factor to determine a patient’s eligibility for surgical resection.
