Abstract
Simple SummaryMalignant pleural mesothelioma (MPM) is a cancer affecting the covering of the lung (the pleura). This commonly causes a build-up of fluid around the lung, called a pleural effusion. Draining the pleural effusion can improve breathlessness and tests can be performed on the fluid. However, for most patients with MPM, a sample of tissue from the pleura, called a biopsy, is required in addition to make the diagnosis. Sometimes, due to medical conditions, frailty or personal preference, patients may not be able to have a biopsy. This review article discusses additional tests used in this situation to help doctors make a diagnosis of MPM. These techniques include tests on pleural fluid using “immunocytochemistry” methods, biomarkers and scans. Although, without a biopsy, no test in isolation can diagnose MPM, combining information from different types of tests and reviewing results among a specialist team can enable a consensus diagnosis.For a number of patients presenting with an undiagnosed pleural effusion, frailty, medical co-morbidity or personal choice may preclude the use of pleural biopsy, the gold standard investigation for diagnosis of malignant pleural mesothelioma (MPM). In this review article, we outline the most recent evidence on ancillary diagnostic tests which may be used to support a diagnosis of MPM where histological samples cannot be obtained or where results are non-diagnostic. Immunocytochemical markers, molecular techniques, diagnostic biomarkers and imaging techniques are discussed. No adjunctive test has a sensitivity and specificity profile to support use in isolation; however, correlation of pleural fluid cytology with relevant radiology and supplementary biomarkers can enable an MDT-consensus clinico-radiological-cytological diagnosis to be made where further invasive tests are not possible or not appropriate. Diagnostic challenges surrounding non-epithelioid MPM are recognised, and there is a critical need for reliable and non-invasive investigative tools in this population.
Highlights
Arising predominantly from the pleural or peritoneal surface, mesothelioma grows insidiously, often resulting in an advanced stage at clinical presentation
Whilst research into innovative treatment options is an active area of interest and brings new hope for patients, malignant pleural mesothelioma (MPM) remains relatively refractory to conventional therapies
IHC techniques may be employed, in addition, to detect methylthioadenosine phosphorylase (MTAP) loss, distinguishing malignant from benign proliferations with a specificity of 100% and a sensitivity of 43% in cell block specimens from pleural effusions [37,38]
Summary
Arising predominantly from the pleural or peritoneal surface (less commonly the pericardium and tunica vaginalis), mesothelioma grows insidiously, often resulting in an advanced stage at clinical presentation. Thoracoscopic pleural biopsy is recommended as the gold standard for investigating an undiagnosed pleural effusion where the differential includes MPM, with diagnostic yields of 95% and higher [13]. International guidelines do not advocate cytology-based diagnoses of MPM in patients who are fit for further diagnostic tests [1], the importance of obtaining a diagnosis for frail patients who are unable to undergo invasive procedures to obtain a biopsy is no less significant. We will focus on techniques which may be used to support a diagnosis of MPM from cytological specimens and other less invasive modalities, where histological samples cannot be obtained or where results may be non-diagnostic. Diagnostic cytology on PF can spare the patient more invasive investigations to obtain a tissue biopsy, reducing the risk of procedural complication with both cost and time saving in addition. Recent advances in immunocytochemical and molecular testing have facilitated these diagnostic steps [22,26]
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