Use of cholesterol and soluble tumour markers CEA and syndecan-2 in pleural effusions in cases of inconclusive cytology

Our plain-English summary of Use of cholesterol and soluble tumour markers CEA and syndecan-2 in pleural effusions in cases of inconclusive cytology, by M. Gulyas, J. Fillinger, A.D. Kaposi, et al (Journal of Clinical Pathology, 2019).

The study

• Authors: M. Gulyas, J. Fillinger, A.D. Kaposi, M. Molnar
• Journal: Journal of Clinical Pathology
• Published: 2019;72(8):529-535
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Aims: In order to improve diagnostics in pleural effusions, additional value of effusion cholesterol, carcinoembryonic antigen (CEA) and syndecan-2 assays to cytology was studied.

Methods: Biomarkers were measured in effusion supernatants from 247 patients, of whom 126 had malignant pleural involvement, and their additional diagnostic efficacy to cytology was assessed.

Results: Syndecan-2 measurement, although gave detectable concentrations in all effusions with highest median value in mesotheliomas, was non-discriminative between different pathological conditions. CEA concentrations exceeding 5 ng/mL cut-off point indicated carcinomas, regardless of pleural involvement, which gave a sensitivity of 62% and specificity of 100% for carcinoma. Cholesterol concentration over 1.21 mmol/L cut-off value indicated neoplastic pleural involvement with 99% sensitivity and 'merely' 69% specificity, the latter mainly due to raised levels being associated also with benign inflammatory effusions. Combined CEA and cholesterol determinations increased the sensitivity for diagnosing carcinomatosis from 70% with cytology alone to 84% and established the correct diagnosis in 16 of 31 carcinomatosis cases with inconclusive cytology. Cholesterol measurement alone, with elevated level, in combination with absence of substantial number of inflammatory cells in effusion sediment proved to be a magnificent marker for neoplastic pleural involvement with 99% efficacy, and recognised all 36 such cases with inconclusive cytology.

Conclusions: Simultaneous measurement of CEA and cholesterol concentrations in effusion, or at least cholesterol alone, in combination with non-inflammatory fluid cytology, provides additional specific information about neoplastic pleural involvement, and can therefore be used as an adjunct to cytology, above all, in inconclusive cases.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

In plain English

This diagnostic study at a Budapest lung hospital tested whether measuring cholesterol, carcinoembryonic antigen (CEA) and syndecan-2 in pleural fluid (fluid around the lungs) adds to cytology (cell examination), especially when cytology is inconclusive. Fluid from 247 patients, collected between 2005 and 2012, was analysed. Of these, 126 had cancer involving the pleura, including 17 with malignant mesothelioma. The article does not address asbestos exposure. Cytology was inconclusive in 53 cases. All 81 fluids with CEA above 5 ng/mL came from patients with a carcinoma, and all 17 mesotheliomas had low CEA. Cholesterol above 1.21 mmol/L was raised in 125 of 126 cases with cancer in the pleura, but also in inflammatory effusions. Among patients without pleural inflammation, cholesterol was correct in 208 of 210 and flagged all 36 inconclusive-cytology cases with cancer in the pleura. Syndecan-2 was detectable in all 179 fluids tested, with the highest median in mesothelioma, but did not separate the disease groups. The authors concluded that CEA plus cholesterol, or at least cholesterol alone, combined with fluid cytology showing no inflammation, can be an adjunct to cytology, above all in inconclusive cases.

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: Diagnostic accuracy study of pleural fluid biomarkers compared against histology. The ethics statement calls it a retrospective study of routinely collected samples.
• Who was studied: Pleural effusions from 247 patients (147 men aged 22–88, 100 women aged 23–88) admitted to Korányi National Institute for Pulmonology, Budapest, Hungary, with samples collected between 2005 and 2012. 126 had malignant pleural involvement (106 carcinomas, 17 malignant mesotheliomas, 3 other malignancies), 26 had cancer without pleural involvement, and 95 had benign conditions. Syndecan-2 was measured in a subset of 179.
• Exposure: No asbestos or other environmental or occupational exposure was studied. The study measured cholesterol, CEA and syndecan-2 in pleural fluid as diagnostic markers.
• Main results:
  • Cytology was inconclusive in 53 of 247 cases (21%). Of these, 36 proved to have malignant pleural involvement (five mesotheliomas and 31 carcinomas), six had carcinoma without carcinomatosis, and 11 had no tumour.
  • Using a CEA cut-off of 5 ng/mL, CEA had a specificity of 100% (95% CI 96.9 to 100) and a sensitivity of 62.3% (95% CI 53.4 to 70.7) for carcinoma, regardless of pleural involvement.
  • All 17 mesotheliomas and five other non-epithelial malignancies had low CEA levels.
  • Using a cholesterol cut-off of 1.21 mmol/L, cholesterol had a sensitivity of 99.2% (125/126) and a specificity of 69.4% (84/121) for neoplastic pleural involvement.
  • Raised cholesterol was also seen in benign effusions, mostly inflammatory ones (purulent or tuberculous pleurisy).
  • Adding combined cholesterol and CEA to cytology increased the sensitivity for carcinomatosis from 69.8% (cytology alone) to 84.1%.
  • Both markers were raised in 16 of the 31 carcinomatosis cases with inconclusive cytology, a sensitivity of 51.6% (95% CI 33.1 to 69.9) among those cases.
  • In the 210 patients without pleural inflammation, raised cholesterol combined with non-inflammatory cytology had an efficacy of 99.0% (208/210). It recognised all 36 cases with inconclusive cytology that had tumour involving the pleura.
  • Syndecan-2 (measured in 179 effusions) was above 0.9 ug/mL in all of them, with no obvious separation between conditions.
  • The mesothelioma group had the highest median syndecan-2 value, with all its concentrations above 10 ug/mL.
• The authors' conclusion: The authors concluded that measuring CEA and cholesterol together in pleural fluid, or at least cholesterol alone, combined with non-inflammatory cytology, provides additional specific information about neoplastic pleural involvement. They said it can be used as an adjunct to cytology, above all in inconclusive cases. They also concluded that syndecan-2 did not discriminate between conditions.
• Limitations the authors state:
  • The authors describe the mesothelioma group as relatively small.
  • For carcinoma cases with raised CEA but no pleural carcinomatosis, the authors state that undetected metastases cannot be ruled out.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Cytology, Carcinoembryonic Antigen (CEA), Biomarker, Mesothelioma, Carcinoma, Fluid Cytology.

Related studies

• Evaluation of soluble mesothelin-related peptide as a diagnostic marker of malignant pleural mesothelioma effusions: its contribution to cytology — P.A. Canessa, M.C. Franceschini, et al. (2013)
• The diagnostic utility of D2-40, calretinin, CK5/6, desmin and MOC-31 in the differentiation of mesothelioma from adenocarcinoma in pleural effusion cytology — T.S. Hyun, M. Barnes, et al. (2012)
• EZH2, a unique marker of malignancy in effusion cytology — H. Jiang, R. Gupta, et al. (2014)
• Claudin-4 immunohistochemistry is highly effective in distinguishing adenocarcinoma from malignant mesothelioma in effusion cytology — V.Y. Jo, E.S. Cibas, et al. (2014)
• Loss of expression of BAP1 is a useful adjunct, which strongly supports the diagnosis of mesothelioma in effusion cytology — J. Andrici, A. Sheen, et al. (2015)
• MMP-7 is a highly specific negative marker for benign and malignant mesothelial cells in serous effusions — B. Davidson, H.T. Stavnes, et al. (2016)

Browse more research in Journal of Clinical Pathology, or return to medical research.