In this article, we will discuss Malignant Pleural Mesothelioma (Clinical Manifestations, Investigation and Diagnosis). So, let’s get started.
Clinical manifestadions, Investigation and Diagnosis
Chest radiological imaging should be performed in all MPM-suspected patients for diagnostic and staging information. Characteristically radiological findings may be nodular pleural thickening, pleural plaques, a localized pleural-mass lesion, pleural
effusion, irregular fissural thickening, or loss of hemithoracic volume.
Nevertheless, further radiologically imaging tools, such as bedside
chest ultrasonography, computed tomographic imaging are usually
required due to insensitive and nonspecific chest radiographic features in general. Positron-emission technology-computed tomography
(PET-CT) combines high-resolution computed tomographic (CT)
Scanning injected with a radioactive metabolic tracer (such as
18-fluoro-deoxy-glucose (FDG) or magnctic resonance imaging
(MRI). Nevertheless, PET-CT has low sensitivity for the diagnosis of extrapleural lesions due to its poor spatial resolution. In addition to CT scanning of the chest, surgical information by video assisted thoracoscopic surgery (VATS) plus mecdiastinoscopy which is the current gold standard for staging in MPM and is superior to CT for assessing tumor size and suspected nodal metastasis, is the consensus by using the International Mesothelioma Interest Group staging classiication, whereas the European Pneumological Society recommends using the tumor-nodes-metastases (TNM)
classification of the Union for International Cancer Control (UICC). VATS reveals the sensitivity and specificity of 95-98% and 100%, respectively and enables the removal of specimens unde visual
observation, as well as pleurodesis in the same procedure. VATS also enables the assessment of its respectability.
By pleural puncture and cytological diagnosis tumor cells are identitied in pleural eftusion more than 50% of patients with MPM with the likelihood of positive cytology depending on the MPM subtype with the limited cytological diagnosis. Percutaneous needle biopsy without imape guidance reveals the sensitvity and specificity of 7-47% and 100% respectively.
There are several circulating tumor proieins identified in patients with MPM such as mesothelin (MSLN, a cell-surface glycoprotein expressed by mesothelial cells), osteopointin (an integrin-binding protein implicated in cell-matrix interaction and overexpressed in several types of cancers), and fibulin-3 (a secreted glycoprotein implicated in cell proliferation and migration correlated with advanced
disease, also identified in pleural fuid). a Soluble mesothelin-related peptide (SMRP), a soluble form of mesothelin is secreted by the tumor cells into the blood circulation SMRP seems to be effective in predicting response to chemotherapy and patient survival although it is not specific for MPM and cannot be considered an early diagnostic biomarkers for MPM surveillance program. Several studies revealed that plasma osteopontin is a more reliable and stable biomarker than serum osteopontin and the data involving its diagnostic accuracy are inadequate. Combined measurement of circulating SMRP and osteopontin is not more informative than measurement of circulating SMRP alone, Several previous studies demonstrated that fibulin-3 was not beneficial for difierentiating patients with MPM from patients affected by other diseases. and was not effective as mesothelin.
Other biomarkers for detecting MPM are inflammatory and angiogenic factors (High Mobility Group B1 (HMGB1) and (VEGF) biomarkers of oxidative stress (Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS), circulating micro-ribonucleic acids (miRNAS), circulating tumor deoxyribonucleic acid (ctDNA), Circulating methylated deoxyribonucleic acid (circulating methylated DNA), and circulating tumor cells (CTCs).A previous study indicated that HMGB1 and its receptors were highly expressed in MPM cell lines and tissues. EGH a key stimulator of tumor neoangiogenesIs is overexpressed in MPM tissues. In comparison to patients with lung cancer or non-malignant pleural diseases circulating VEGF levels are increased in pleural effusions of patients with MPM. ROS and RNS are key mediators of asbestos toxicity. Bronchoalveolar lavage (BALF) of patients with asbestos exposure demonstrated an increase in various biomarkers of infiammation and altered ROS and iron homeostasis (i.e., iron, lactoferrin, ferritin, transferrin, and transferrin receptors)compared to controlsA previous study on the levels of miR-103a-3p and miR-30e-3p in extracellular vesicles demonstrated that the combination of these two biomarkers discriminated patients with MPM from asbestos-exposed controls with a sensitivity of 95.5% and specificity of 80% and were confirmed by normalizing the data to RNU48, miR-99a, miR-638, miR-720, and miR-1274a. In consideration, these miRNAs could be biomarkers of asbestos exposure rather than disease. Upregulation ofmiR-2053 could be a good prognostic biomarker of MPM. Detection of ctDNA variants in patients with MPM could be a potential biomarker for the
diagnosis of MPM. Detection of changes in ctDNA methylation could be an early diagnostic and prognostic tool of MPM. CTCs counts in the blood circulation is very low at the early stage and increases in advanced stage of cancer.
Chest pain is common and usually heavy and dull and sometime called a dragging sensation Breathlessness is also common and is usually due to a pleural effusion that is identified in about 70% of MPM patients in early stage of disease. Other clinical features include anorexia, weight loss, malaise, sweats, and fatigue.