Diagnostic method for malignant pleural effusion distinguishing malignant mesothelioma from lung cancer using pleural carcinoembryonic antigen and hyaluronic acid levels

Our plain-English summary of Diagnostic method for malignant pleural effusion distinguishing malignant mesothelioma from lung cancer using pleural carcinoembryonic antigen and hyaluronic acid levels, by T. Saraya, K. Ohkuma, M. Fujiwara, et al (Medicine, 2022).

The study

• Authors: T. Saraya, K. Ohkuma, M. Fujiwara, H. Ishii
• Journal: Medicine
• Published: 2022;101(1):e28517
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MM) is difficult to diagnose because of the lack of parenchymal opacities, often revealing minimal or absent pleural thickening. Furthermore, pleural effusion has diverse differential diagnoses, including malignancies, infections, as well as collagen vascular and other benign diseases. In general practice, lung cancer (LC) is the most common malignancy causing pleural effusion; therefore, a simple method using pleural diagnostic markers to differentiate between LC and mesothelioma is crucial.We retrospectively reviewed the data of 530 adult patients diagnosed with pleural effusion between January 2010 and December 2020 in an outpatient or inpatient setting. Patients with pathologically diagnosed MM or LC with cytologically positive (class IV or V) pleural effusion were analyzed, and the characteristics of these 2 diseases were compared.During the study period, 27 patients diagnosed with MM and 100 patients diagnosed with LC were enrolled. Receiver operating characteristic curve analysis demonstrated that pleural carcinoembryonic antigen (CEA) and hyaluronic acid (HA) could discriminate MM from LC with an area under the curve of 0.925 (95% confidence interval [CI]: 0.879-0.972, P < .001) and 0.815 (95% CI: 0.686-0.943, P < .001), respectively. To diagnose MM, the accuracy of pleural HA >30,000 ng/mL revealed a sensitivity of 75.0%, specificity of 72.6%, and odds ratio of 7.94 (95% CI: 2.5-25.2, P = .001); pleural CEA <6.0 ng/mL revealed a sensitivity of 95.2%, specificity of 84.9%, smaller negative likelihood ratio of 0.06, and odds ratio of 112.5% (95% CI: 14.4-878.1, P < .001). Multiple logistic regression analysis revealed that these 2 parameters could discriminate MM from LC, with a hazard ratio of 23.6 (95% CI: 2.437-228.1, P = .006) and 252.3 (95% Cl: 16.4-3888.1, P < .001), respectively, and their combination had a high specificity of 98.3%.Pleural CEA (≥6.0 ng/mL) can rule out MM with a high degree of certainty, and the positive results for combination of pleural CEA <6.0 ng/mL and HA >30,000 ng/mL can confirm MM with high specificity, prior to cytological or pathological examinations.

Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.

In plain English

This retrospective study at a 1,100-bed Tokyo hospital asked whether two substances in the fluid around the lungs (pleural effusion) could distinguish malignant mesothelioma from lung cancer. The authors reviewed 530 adults with pleural effusion seen from January 2010 to December 2020. They included those whose fluid tested positive for cancer cells: 27 with mesothelioma and 173 with lung cancer (the abstract says 100). Mesothelioma patients had lower fluid levels of carcinoembryonic antigen (CEA) and higher levels of hyaluronic acid (HA). CEA below 6.0 ng/mL identified mesothelioma with 95.2% sensitivity and 84.9% specificity. HA above 30,000 ng/mL gave 75.0% and 72.6%. Both together gave 98.3% specificity and 68.4% sensitivity. The authors concluded that CEA of 6.0 ng/mL or more can rule out mesothelioma with high certainty and that the combination can confirm it with high specificity. They noted the study was retrospective and had few mesothelioma patients. It also included only cytology-positive cases, which they said overestimates the markers' accuracy. Asbestos exposure was not reported.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective, single-center observational study of diagnostic markers in pleural fluid
• Who was studied: Out of 530 adults with pleural effusion at an 1100-bed tertiary care center in Tokyo (January 2010 to December 2020), 200 patients with malignant pleural effusion were enrolled: 27 with pathologically diagnosed malignant mesothelioma (13 epithelial, 2 biphasic, 3 desmoplastic, 9 unclassified) and 173 with lung cancer (152 adenocarcinoma). All had cytologically positive (class IV or V) effusion. Men to women: 25/2 in the mesothelioma group and 106/67 in the lung cancer group.
• Exposure: The study did not examine asbestos exposure, fiber types or occupations. What it measured was levels of carcinoembryonic antigen (CEA) and hyaluronic acid (HA) in pleural fluid.
• Main results:
  • Median pleural CEA was 1.4 ng/mL (IQR 1.1 to 1.6) in the mesothelioma group and 196 (IQR 102 to 198) in the lung cancer group (P<.001).
  • Median pleural hyaluronic acid was higher in the mesothelioma group (given as 111,990 in the text and 111,900 in Table 1; IQR 30,800 to 193,000 ng/mL) than in the lung cancer group (median 8850, IQR 8355 to 13,325; P<.001).
  • In receiver operating characteristic analysis, the area under the curve for distinguishing mesothelioma from lung cancer was 0.925 for pleural CEA (95% CI 0.879 to 0.972, P<.001) and 0.815 for pleural HA (95% CI 0.686 to 0.943, P<.001).
  • Pleural CEA below 6.0 ng/mL gave a sensitivity of 95.2% and a specificity of 84.9% for mesothelioma. The odds ratio was printed as '112.5%' (95% CI 14.4 to 878.1, P<.001). Table 2 gives a negative likelihood ratio of 0.06 and a negative predictive value of 99.2.
  • Pleural HA above 30,000 ng/mL gave a sensitivity of 75.0% and a specificity of 72.6%, with an odds ratio of 7.94 (95% CI 2.5 to 25.2, P=.001).
  • When both CEA below 6.0 ng/mL and HA above 30,000 ng/mL were present, sensitivity was 68.4%, specificity 98.3%, positive likelihood ratio 40.2, and odds ratio 127.8 (95% CI 14.2 to 1154.3, P<.001).
  • In multiple logistic regression, the reported 'hazard ratios' for distinguishing mesothelioma from lung cancer were 252.3 for CEA below 6.0 ng/mL (95% CI 16.4 to 3888.1, P<.001) and 23.6 for HA above 30,000 ng/mL (95% CI 2.437 to 228.1, P=.006).
  • Hyaluronic acid results were available for only 18 mesothelioma patients. Levels were comparable between 5 non-epithelioid cases (biphasic and desmoplastic; median 44,178 ng/mL) and 13 epithelioid cases (median 31,185; P=.643).
• The authors' conclusion: The authors concluded that pleural CEA of 6.0 ng/mL or more can rule out malignant mesothelioma with a high degree of certainty. They also concluded that positive results for both CEA below 6.0 ng/mL and HA above 30,000 ng/mL can confirm mesothelioma with high specificity before cytological or pathological examination.
• Limitations the authors state:
  • The study was retrospective.
  • Relatively few mesothelioma patients were enrolled because the disease is uncommon.
  • All enrolled patients were cytologically positive (class IV or V), which the authors said overestimates the diagnostic yield of the markers.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Mesothelioma, Lung Cancer, Carcinoembryonic Antigen (CEA), Hyaluronic Acid, Pleural Thickening, Collagen, confidence interval.

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