In the diagnosis of malignant mesothelioma targeted and judicious use of laboratory tests as well as imaging studies is warranted. The results of these diagnostic tests will ultimately impact the staging and prognosis of the disease.
At present, the reference biochemical marker used in the diagnosis of malignant mesothelioma is serum soluble mesothelin. A cut-off value of 2.00 nmol/L is the reference limit and has a 95% specificity and 64% sensitivity rates. An emerging biochemical marker for the diagnosis of malignant mesotheliomas is megakaryocyte potentiating factor (MPF). This comes from the same parent compound as soluble mesothelin. Megakaryocyte potentiating factor has a reference limit of 12.38 ng/ml for diagnosis with a sensitivity rate of 68%. The combination of both biochemical markers did not show any increase in the diagnostic power for malignant mesothelioma.
Pleural fluid findings among patients with malignant mesothelioma usually show a typical profile. This consists of an elevated white cell count (1000 leukocytes/liter), elevated protein, a few erythrocytes and normal lactate dehydrogenase levels. Cytologic examination of pleural fluid may also reveal some of the malignant cells. However, both of these examinations are non diagnostic for malignant mesothelioma.
Biopsy of pleural tissue using thoracoscopy or pleuroscopy remains to be the gold standard in diagnosing malignant mesothelioma. The use of proper staining techniques contributes a great deal to deciphering the correct histologic subtype. This in turn impacts greatly the prognosis of the disease for each individual patient.
It is imperative to distinguish malignant mesothelioma from the various types of lung cancer, particularly adenocarcinoma. The stark differences in management and prognosis for each disease dictate that the right diagnosis be made. Under electron microscopy, malignant mesothelioma shows long microvilli, whereas adenocarcinomas reveal short ones. These two disease entities also vary in their reaction profile to a variety of stains. Malignant mesothelioma shows negative results in staining with periodic acid Schiff (PAS), mucicarmine, for carcinoembryonic antigen (CEA), and Leu M1, while adenocarcinoma reveals positive results for these. Malignant mesothelioma on the other hand shows positive results in staining for vimentin, cytokeratin, and calretinin. Levels of circulating serum mesothelin related protein (SMRP) have also been found to be elevated in 84% of patients with malignant mesothelioma. Whereas among patients with lung cancer, only 2% were found to have elevated levels of the same.
Malignant mesothelioma must also be distinguished from simple effusions of reactive mesothelial cells. In this regard, fluorescence in situ hybridization (FISH) plays a very significant role. Detection of chromosomal aberrations indicative of malignant mesothelioma, e.g. loss of a single copy of chromosome 22, and chromosome 6 abnormalities to name a few, by FISH has a sensitivity rate of 79%. FISH also has a positive predictive value of 100% and a negative predictive value of 72% in the detection of mesothelioma.
The use of imaging studies such as chest radiographs, CT scans, MRIs, and PET scans also render value to the final staging of the disease. Baseline lung functions including diffusion capacity should be included in the preoperative evaluation of the patient. A stress test using pharmacologic agents is a good way to rule out the presence of silent myocardial ischemia.
The TNM classification for the staging of malignant mesothelioma is the one widely used by physicians. The staging runs from I through IV. Stage I is assigned when the disease is confined to the capsule of the parietal pleura, is completely resectable, and with no presence of adenopathy. Stage II is assigned when resection margins are positive for tumor cells or there are intrapleural adenopathy detected, or the presence of both. When the disease has infiltrated through to the chest wall, mediastinum, heart, diaphragm, peritoneum or to lymph nodes outside of the pleura, then Stage III is assigned. With distant metastases present, Stage IV is assigned. Choice of treatment is tailored according to the stage of disease at diagnosis.
The presence of the following factors usually spell a poorer prognosis in patients with malignant mesothelioma: male sex, age older than 75, presence of chest pain, weight loss, high platelet count, high WBC count, low hemoglobin, LDH levels greater than 500 IU/L, and a non-epitheloid histology.
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