Distinguishing benign from malignant mesothelial cells in effusions by Glut-1, EMA, and Desmin expression: an evidence-based approach

Our plain-English summary of Distinguishing benign from malignant mesothelial cells in effusions by Glut-1, EMA, and Desmin expression: an evidence-based approach, by M. Kuperman, R.R. Florence, L. Pantanowitz, et al (Diagnostic Cytopathology, 2013).

The study

• Authors: M. Kuperman, R.R. Florence, L. Pantanowitz, P.F. Visintainer, E.S. Cibas, C.N. Otis
• Journal: Diagnostic Cytopathology
• Published: 2013;41(2):131-40
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Distinguishing malignant mesothelioma (MM) from reactive mesothelial hyperplasia (RM) may be difficult in effusions. This study tested the hypothesis that immunocytochemistry (IC) in effusion cell blocks (CB) can distinguish MM from RM and that the results may be applied to individual specimens. External validation of a risk score (RS) model associating sensitivity and specificity was applied to an external set of MM and RM specimens from a separate institution. Forty three effusion cytology CBs of 25 confirmed malignant mesotheliomas were compared to CBs of 23 benign mesothelial effusions without inflammation and 13 reactive mesothelial proliferations associated with inflammation. Glut-1, EMA, and Desmin expression were evaluated by immunocytochemistry on CBs. Each antibody was compared using ROC values, where the area under the curve (AUC) was 0.90, 0.82, and 0.84 for Glut-1, EMA, and Desmin, respectively. Logistic regression (LR) analysis was applied to a combination of Glut-1 and EMA. A combined ROC curve was modeled for Glut-1 and EMA (AUC = 0.93). A RS = 2 × (Glut-1%) + 1 × (EMA%) was created from this ROC curve. When applied to an external set of MM and RM, the RS resulted in an ROC with AUC = 0.91. In conclusion, a RS derived from a LR of Glut-1 and EMA IC greatly improves the distinction between MM from RM cells in individual effusions. The study illustrates principles of evidence-based pathology concerning internal and external test performance in the differential diagnosis of MM versus RM.

Copyright © 2011 Wiley Periodicals, Inc.

In plain English

This study tested whether staining cells from body-cavity fluid (effusions) for Glut-1, EMA and desmin could distinguish malignant mesothelioma from benign, reactive mesothelial cells. Asbestos exposure was not studied. At Baystate Health Systems, the authors examined 43 samples from 25 patients with surgically confirmed mesothelioma (23 pleural, 2 peritoneal). They compared these with benign effusions with and without inflammation. Used alone, areas under the curve (with 95% confidence intervals) were 0.90 for Glut-1 (0.82 to 0.97), 0.82 for EMA (0.73 to 0.91) and 0.84 for desmin (0.75 to 0.93). Glut-1 and EMA combined gave 0.93 (0.87 to 0.99). A risk score was built: twice the Glut-1 grade plus the EMA grade, ranging from 0 to 12. At a score of 7, Baystate sensitivity was 70% and specificity 94%. In 35 mesothelioma and 37 benign cases from Brigham and Women's Hospital, the figures were 63% and 95%. The authors concluded the score greatly improves the distinction in individual effusions. They noted that sensitivity was about 60 to 70% at high specificity, that interobserver and interassay variability were not assessed, and that further validation is needed.

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 diagnostic accuracy study of archived effusion cell blocks, with external validation on cases from a second institution
• Who was studied: The Baystate Health Systems cases (1995 to 2008) fell into three groups. The first was 25 malignant mesothelioma cases confirmed by surgical specimens: 23 pleural and 2 peritoneal; 19 epithelial, 3 biphasic and 3 desmoplastic; ages 33 to 81; male to female ratio 22:3. These contributed 43 effusion samples, although the methods say 46. The second was benign mesothelial proliferations without inflammation: 22 cases in the methods, 23 in the abstract. The third was 13 florid reactive pleural cases with inflammation. The external set came from Brigham and Women's Hospital (2000 to 2006): 35 malignant mesothelioma cases (28 epithelioid, 7 biphasic) and 37 benign cases.
• Exposure: No asbestos exposure was studied. What was tested was immunostaining of effusion cell blocks for Glut-1, desmin and EMA. Each stain was graded 0 to 4 by the percentage of stained cells.
• Main results:
  • In the Baystate cases, the area under the ROC curve for each single stain (malignant mesothelioma vs benign effusions) was 0.90 for Glut-1 (95% CI 0.82, 0.97), 0.82 for EMA (0.73, 0.91) and 0.84 for desmin (0.75, 0.93).
  • In the Baystate cases, Glut-1 and EMA combined gave an area under the curve of 0.93 (95% CI 0.87 to 0.99) for malignant mesothelioma versus all benign effusions combined.
  • The combined Glut-1 and EMA area under the curve was 0.97 (95% CI 0.94 to 1.00) against the benign group without inflammation only. Against the reactive/inflammatory group only, it was 0.86 (0.73 to 0.99).
  • The risk score was 2 times the Glut-1 grade plus 1 times the EMA grade, with a theoretical range of 0 to 12.
  • In the Baystate cases, a risk score of 7 corresponded to 70% sensitivity and 94% specificity for malignant mesothelioma versus benign effusions.
  • In the external Brigham and Women's Hospital cases, a risk score of 7 gave 63% sensitivity and 95% specificity.
  • Applied to the external set, the risk score gave an area under the curve of 0.91.
• The authors' conclusion: The authors concluded that a risk score derived from Glut-1 and EMA staining greatly improves the distinction between malignant mesothelioma and reactive mesothelial cells in individual effusions. They added that the approach still requires further validation.
• Limitations the authors state:
  • Interobserver and interassay variability were not assessed.
  • Sensitivity was only about 60 to 70% when specificity reached 90% or greater.
  • The approach was tested on only one external set and requires further validation.
  • Glut-1 staining of red blood cells obscured the mesothelial cell signal in bloody effusions.

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: Mesothelial Cells, Desmin, Malignant Mesothelioma, Reactive Mesothelial Hyperplasia, Cell Block, Cytology, Inflammation, Pathology.

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• Diagnostic value of BRCA1-associated protein-1, glucose transporter-1 and desmin expression in the discrimination between reactive mesothelial proliferation and malignant mesothelioma in tissues and effusions — S. Önder, E. Özogul, et al. (2019)
• Practical utility of insulin-like growth factor II mRNA-binding protein 3, glucose transporter 1, and epithelial membrane antigen for distinguishing malignant mesotheliomas from benign mesothelial proliferations — S. Chang, M.H. Oh, et al. (2014)
• IMP3 and GLUT-1 immunohistochemistry for distinguishing benign from malignant mesothelial proliferations — A.F. Lee, A.M. Gown, et al. (2013)
• How useful is GLUT-1 in differentiating mesothelial hyperplasia and fibrosing pleuritis from epithelioid and sarcomatoid mesotheliomas? An international collaborative study — A.N. Husain, M.K. Mirza, et al. (2014)

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