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One of the major challenges of mesothelioma is early or earlier diagnosis. Mesothelioma causes pleural effusion or fluid build-up between the layers of the lining of the lung cavity in about 70% of its cases.1 About 1.5 million people are diagnosed with pleural effusion in the US each year. Since about 3000 cases of mesothelioma are diagnosed each year, most cases of pleural effusions are not due to mesothelioma. However, finding mesothelioma in the pleural effusion or pleural soup could provide an early or earlier diagnosis.
Basics About Pleural Effusions
Pleural effusions between the layers of the lining of the lung cavity can be caused by congestive heart failure, inflammation from pneumonia or autoimmune diseases, lung injury, liver disease, poor kidney function, and tumors. The tumor types most frequently causing pleural effusions included lung adenocarcinoma (cancer that forms in mucus-secreting glands) (44%), breast cancer (24.4%) and mesothelioma (12.2%).2 Doctors suspect that patients with a dry cough, shortness of breath, chest pain, and abnormal “fluidy” sounds with a stethoscope or tapping on the chest may have pleural effusion. The presence of pleural effusion is usually confirmed with a chest X-ray, ultrasound imaging, or a CT scan. When pleural effusion is present, a physician takes a sample to determine the cause of the excess fluid and can also drain it to decrease the patient’s symptoms.
The Search for Tumor Cells and Their Identification
Pleural effusions are checked for cancer-looking cell types and for markers of adenocarcinoma and mesothelioma.3 One panel of antibodies can distinguish normal mesothelial cells from cancer cells in the pleural effusion and the tumors cells as an adenocarcinoma (lung or breast cancer) and a mesothelioma most of the time (79%).3 The panel includes antibodies for markers only on the lung cancer and those only on the mesothelioma.3
Tumors Have High Telomerase Activity
However, telomerase, an enzyme that helps replicate the ends of the chromosomes, is often very active in cancer cells.4 Scientists use an assay called the Telomere Repeat Amplification Protocol (TRAP) that amplifies the telomerase activity. They found that pleural effusions from noncancerous patients (benign diagnosis; 7 of 7) showed background levels of telomerase activity. In contrast, 8 samples from 23 pleural effusions from patients with cancer showed telomerase activity, suggesting that telomerase activity in pleural effusions may help provide an earlier diagnosis of malignancy in some difficult samples, including challenging samples from some mesothelioma patients.4
Using Cytology and Pleural Solutions for Early Diagnoses
A recent preliminary report presented at the Royal College of Pathologists of Australasia meeting suggests that cytology—how a cell looks—can also help diagnose mesothelioma in pleural effusions.1 Many of the epithelioid mesothelioma cells in the pleural effusion samples showed some or all of the following characteristics: (1) cells containing more than one nucleus; (2) one or two nucleoli in a round or oval nucleus; (3) thick basophilic cytoplasm; (4) stroma of type 2 collagen; (4) hump-like processes; (5) clumps of cells; and (6) muddling contour of cells.1
Benefits of Earlier Diagnoses of Mesothelioma
Overall survival rates for patients diagnosed with early stages of mesothelioma are usually longer. Thus, methods that improve the sensitivity of diagnosis of mesothelioma are hotly pursued topics in the mesothelioma field and can directly impact the treatment and overall survival of future patients.
>Kawai T, Hiroshima K, Kamei T. Pulmonary Pathology: SY22-2 Diagnosis of mesothelioma by cytology using Japanese criteria Pathology 2014;46 Suppl 2S39.
Anevlavis S, Kouliatsis G, Sotiriou I et al. Prognostic factors in patients presenting with pleural effusion revealing malignancy. Respiration 2014;87(4):311-316.
Dejmek A, Hjerpe A. The combination of CEA, EMA, and BerEp4 and hyaluronan analysis specifically identifies 79% of all histologically verified mesotheliomas causing an effusion. Diagn Cytopathol 2005;32(3):160-166.
Adell E, Dejmek A. Telomerase activity analyzed with trap in situ provides additional information in effusions remaining equivocal after immunocytochemistry and hyaluronan analysis. Diagn Cytopathol 2014. URL: http://www.ncbi.nlm.nih.gov/pubmed/24692425