Clinical Presentation of Malignant Pleural Mesothelioma

Mesothelioma typically affects men in their 50s to 70s due to the very long (25- to 50-year) latency period between occupational asbestos exposure and the development of the tumor. Table 1 lists the most common industries identified in over one thousand cases of histologically confirmed mesothelioma cases. Women and children can have the disease, but the male to female ratio is approximately between 3 and 5 to 1.

The duration of symptoms varies; however, the range can extend from two weeks to two years, with most series having a median time to diagnosis from symptoms of 2 to 3 months.  As many as 25% of patients with the disease have symptoms for six months or more before seeking medical attention.  The right side is affected more than the left side (60% vs. 40%), most likely due to the right side’s greater volume.

Approximately sixty percent of the patients present with nonpleuritic chest pain that classically is located posterolaterally and low in the thorax.  Dyspnea (difficulty breathing) is present in fifty to seventy percent of the cases.  Eighty percent of patients present with dyspnea (difficulty breathing) and effusion (fluid surrounding the lung).  The presence of a pleural effusion is documented at some time in the course of the disease in 95% of patients with malignant pleural mesothelioma (MPM). Approximately five percent of patients also have metastatic disease at presentation, usually to the lungs.

Physical examination usually reveals signs associated with a pleural effusion, with decreased breath sounds, dullness to percussion, or decreased motion of the involved chest wall.  Failure to significantly relieve the dyspnea after thoracentesis (draining fluid with a needle) may be an indication of fixation of a nonexpanding, contracted, and trapped lung.  In the late stages of the disease, there is often dramatic cachexia (wasting syndrome), marked contraction of the involved chest with narrowed interspaces, and hypertrophy of the contralateral hemithorax. A chest wall mass occurs in up to 25% of patients, often at the site(s) of prior thoracentesis, thoracotomy, or thoracoscopy wounds.

The workup of the patient with mesothelioma may reveal nonspecific laboratory findings, including hypergammaglobulinemia, eosinophilia, and/or anemia of chronic disease.  It has been recently noted that 14% to 15% of patients have elevated homocysteine levels, reflecting folic acid deficiency (vitamin B₉ or folacin); 17% have biochemical evidence of vitamin B₁₂ deficiency; and 32% have biochemical signs of vitamin B₆ deficiency.  The most striking laboratory abnormality is thrombocytosis (greater than 400,000), which is seen in 60% to 90% of patients, and approximately 15% of patients have platelet (thrombocytes) counts greater than 1,000,000.  At this time unfortunately serum markers (blood tests) that are both sensitive and specific for mesothelioma do not exist.

Malignant mesothelioma can have a diverse radiographic appearance.  Many of the early changes are associated with a previous exposure to asbestos, consisting both of pleural and parenchymal changes, including pleural plaques or parenchymal pulmonary fibrosis.

The most common chest radiography features associated with mesothelioma progression and symptoms include the presence of a pleural effusion, diffuse pleural thickening, and nodularity. The involved hemithorax can eventually have smooth, lobular pleural masses that infiltrate the pleural space and fissures in 45% to 60% of patients with contraction and fixation of the chest. The lung becomes encased, and the mediastinum shifts due to volume loss. The effusion can be loculated, chiefly in the lower portion of the chest, completely obscuring a view of the diaphragm, lower lobes, and pericardium. In many of these instances, the lower lobe is viewed on computed tomography (CT) to be completely collapsed.

Chest tomography allows for density resolution that is not available with chest radiography, and these characteristics are useful not only in the evaluation of the patient with mesothelioma but also with asbestos-related diseases. Pleural changes on chest tomography include pleural plaques, diffuse pleural thickening, and pleural effusion. Additional CT features of mesothelioma include localized nodular or plaque-like pleural thickening, possibly associated with pleural effusion. The lobulated pleural encasement frequently causes lower lobe collapse. Intrapulmonary nodules can occur in 60% of patients, and infiltration into fissures along with enlarged hilar and mediastinal lymph nodes may be seen. The CT allows a better view of the involved pericardium, which is irregularly thickened and associated with infiltration to the pericardial fat pad.  A clear fat plane between the inferior diaphragmatic surface and the adjacent abdominal organs as well as a smooth inferior diaphragmatic contour may imply resectability. CT may reveal a hemidiaphragm encased by a mass or poor definition between the liver, stomach, and inferior diaphragmatic surface.

Magnetic resonance imaging (MRI) is appealing due to the differential signal intensity, depending on the sequence used and the ability to image in the coronal, sagittal, and transverse planes.  Studies have suggested gadolinium contrast enhancement MRI can improve tumor detection and extension. Detection of diaphragm invasion and invasion of endothoracic fascia or a single chest wall focus may be better with MRI compared to CT.

There are a number of studies of positron emission tomography (PET) and the radionuclide imaging agent [¹⁸F]fluorodeoxyglucose (FDG) in mesothelioma. Four studies have reported that FDG-PET is accurate in the diagnosis of pleural malignancies, specifically mesothelioma, and that it may be superior to CT for defining mediastinal lymph node involvement.  Moreover, the ability to define extrathoracic (outside the chest area), otherwise occult (hidden) disease in newly diagnosed patients can be as high as 10% to 45% who are followed after therapy.  Some studies show that the standard uptake value (SUV) of the tumor before resection (surgical removal) can discriminate longer- from shorter-surviving patients and stratify good risk versus bad risk patients. Those with low SUV and epithelial histology have the best prognosis, whereas those with high SUV and nonepithelial histology fare the worst.

After extrapleural pneumonectomy (EPP), CT scanning of the resected hemithorax reveals a smooth-walled, well-defined postoperative membrane lining the pneumonectomy space, which is usually concentrically smooth. As the interval from operation to follow-up lengthens, the membrane may actually become thicker. Unexplained, irregular focal thickening at the base of the chest should alert your doctor to a recurrence of disease.  This is especially pronounced in the pleurectomy patient in whom recurrent mesothelioma may start to thicken rapidly and infiltrate the underlying lung.

Other presentations of recurrence include the development of new mediastinal adenopathy (lymph node enlargement) or ascites (fluid buildup) otherwise undetectable by physical examination. The development of asymptomatic abdominal fluid after EPP is an ominous sign and calls for paracentesis. CT usually reveals diaphragmatic thickening or diffuse mesenteric infiltration in these cases.

Besides evaluation of postoperative progression, an important role of follow-up or sequential CT scanning is in the assessment of the response of mesothelioma to chemotherapy.  Multicenter clinical trials require measuring the thickness of the pleural rind at one to three locations on the rind on three separate slices of the CT every 6 to 9 weeks. The total thickness must then decrease by 30% to declare the patient to have responded, whereas progressive disease requires a 20% increase.

Malignant Mesothelioma of the pleura: current surgical pathology