Abstract

Rationale. The diagnosis of pleural malignant mesothelioma (MM) by effusion cytology may be difficult and is currently controversial. Effusion mesothelin levels are increased in patients with MM but the clinical role of this test is uncertain. Objectives. To determine the clinical value of measuring mesothelin levels in pleural effusion supernatant to aid diagnosis of MM. Methods and Measurements. Pleural effusion samples were collected prospectively from 1331 consecutive patients. Mesothelin levels were determined by commercial ELISA in effusions and their relationship to concurrent pathology reporting and final clinical diagnosis was determined. Results. 2156 pleural effusion samples from 1331 individuals were analysed. The final clinical diagnosis was 183 MM, 436 non-MM malignancy, and 712 nonmalignant effusions. Effusion mesothelin had a sensitivity of 67% for MM at 95% specificity. Mesothelin was elevated in over 47% of MM cases in effusions obtained before definitive diagnosis of MM was established. In the setting of inconclusive effusion cytology, effusion mesothelin had a positive predictive value of 79% for MM and 94% for malignancy. Conclusions. A mesothelin-positive pleural effusion, irrespective of the identification of malignant cells, indicates the likely presence of malignancy and adds weight to the clinical rationale for further investigation to establish a malignant diagnosis.

Highlights

  • Pleural malignant mesothelioma (MM) is an aggressive asbestos-induced malignancy

  • Over the 67-month period of the study 2156 consecutive pleural effusion samples were collected from 1331 individuals, approximately 40% of whom were female

  • As the diagnosis of pleural MM can be difficult by effusion cytology or biopsy and may take weeks or months to establish, the use of effusion biomarkers has the potential to aid in diagnosis and to add to clinical decision making

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Summary

Introduction

The diagnosis of MM is often difficult [1] and may take several weeks to months to establish [2]. Current guidelines recommend that a diagnosis be based on demonstration of invasion by tumor cells [3]; not all patients are able to undergo invasive procedures to obtain a biopsy, and even when tissue is obtained diagnosis may still be difficult [4]. In MM, patients often present with a pleural effusion which can be used for diagnostic purposes. There is controversy regarding the cytological analysis of cells from pleural effusions, with sensitivities reported in several studies to be around 30%, the limitation of the technique relates primarily to difficulty in distinguishing MM from benign mesothelial cells [3, 5, 6]. A high sensitivity and specificity can be achieved if a standardized approach to cytodiagnosis is used [7]

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