Malignant Pleural Mesothelioma

23 MALIGNANT PLEURAL MESOTHELIOMA

Hamza Hashmi, MD

A 70-year-old white man with past medical history of hypertension (HTN) and chronic obstructive pulmonary disease (COPD) presents with a persistent cough for the last 2 months. He has a 60 pack-year smoking history. He worked for 20 years as a coal miner. Chest x-ray reveals a moderate size right-sided pleural effusion. Chest computed tomography (CT) confirms a loculated pleural effusion and pleural-based nodules. On thoracentesis, 500 mL of fluid is removed, and analysis reveals exudative effusion without evidence of malignant cells on cytology. What should be the next step in management of this patient?

Learning Objectives:

1. What are the risk factors associated with malignant pleural mesothelioma?

2. What is the diagnostic modality of choice for malignant pleural mesothelioma?

3. What is the ideal treatment approach for resectable non-metastatic malignant pleural mesothelioma?

4. What is the first line of therapy for metastatic malignant pleural mesothelioma?

INCIDENCE

Malignancies involving mesothelial cells that normally line the body cavities, including the pleura, peritoneum, pericardium, and testis, are known as malignant mesothelioma. Pleural involvement is the most common (85%), followed by peritoneum (15%) and pericardium and tunica vaginalis (1%).

Mesothelioma is a rare malignancy with 2,500 new cases diagnosed annually in the United States. It commonly develops in the fifth to seventh decade of life. The male-to-female ratio is 4:1.

RISK FACTORS

Asbestos, particularly the types of amphibole asbestos known as crocidolite and amosite asbestos, is the principal carcinogen implicated in the pathogenesis of malignant pleural mesothelioma.¹ A substantial proportion of patients with malignant pleural mesothelioma are exposed to asbestos in asbestos mills, mines, shipping yards, paper mills, auto parts (asbestos brake lining), railroad repair, and insulation.

Other associations include exposure to radiotherapy (RT) and erionite (mineral found in sand gravel).

Smoking does not increase the increase of mesothelioma, but together with asbestos exposure does significantly increase the risk of lung carcinoma (adenocarcinoma).

PRESENTATION

Dyspnea and non-pleuritic chest wall pain are the most common presenting symptoms of malignant mesothelioma. Chest discomfort, pleuritic pain, easy fatigability, fever, sweats, and weight loss are the other common accompanying symptoms. Metastatic disease is uncommon at presentation.

DIAGNOSTICS

Biochemical Tests

Several biomarkers are selectively elevated in patients with mesothelioma, including soluble mesothelin-related peptides, fibulin-3, and osteopontin. Of these biomarkers, the circulating serum mesothelin receptor protein level has been reported to be elevated in 84% of patients with malignant mesothelioma and in 2% of patients with lung cancer. Although they are not routinely used for diagnosis, these levels can be used to follow response to treatment.

More than 90% of patients with pleural mesothelioma present with pleural effusion. Cytology findings are diagnostic in only 32% of patients. Diagnosis of mesothelioma by detection of chromosomal aberrations with fluorescence in situ hybridization (FISH) has 79% sensitivity; positive and negative predictive values for detection of mesothelioma were 100% and 72%, respectively.

IMAGING STUDIES

Chest radiographs in malignant pleural mesothelioma show obliteration of the diaphragm, nodular thickening of the pleura, and loculated pleural effusion. A CT or magnetic resonance imaging (MRI) scan of the chest or a positron emission tomographic (PET) scan can also be used in the diagnosis of mesothelioma (Figure 23-1). MRI performed with different pulse sequences and gadolinium-based contrast material can offer more details, with improved detection of tumor extension, especially to the chest wall and diaphragm. Although PET scans can provide metabolic and anatomic information, especially for patients with extrathoracic or mediastinal metastasis, the appropriate role of PET scans in the management of malignant mesothelioma is still undefined.

Figure 23-1. A. Chest CT showing malignant pleural mesothelioma with pleural involvement (arrow). B. Chest MRI showing malignant pleural mesothelioma with pleural involvement (arrow).