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Distinguishing benign from malignant mesothelial cells in effusions by Glut-1, EMA, and Desmin expression: an
Michael Kuperman1, Roxanne R Florence, Liron Pantanowitz
1Department of Pathology, Baystate Medical Center, Tufts University School of Medicine, Springfield, Massachusetts 01199, USA.
Insights
Immunocytochemistry (IC) using Glut-1 and EMA reliably distinguishes malignant mesothelioma (MM) from reactive mesothelial hyperplasia (RM) in effusions. A risk score (RS) model derived from these markers shows high accuracy in external validation, aiding differential diagnosis.
Area of Science:
- Cytopathology
- Oncology
- Immunohistochemistry
Background:
- Differentiating malignant mesothelioma (MM) from reactive mesothelial hyperplasia (RM) in effusion cytology is diagnostically challenging.
- Immunocytochemistry (IC) on cell blocks (CB) offers a potential tool for improved diagnostic accuracy.
Purpose of the Study:
- To evaluate the efficacy of IC markers (Glut-1, EMA, Desmin) in distinguishing MM from RM in effusion CBs.
- To develop and externally validate a risk score (RS) model for differential diagnosis.
Main Methods:
- IC analysis of Glut-1, EMA, and Desmin expression in 43 MM and 36 RM effusion CBs.
- Receiver Operating Characteristic (ROC) curve analysis to assess individual marker performance (AUC).
- Logistic regression (LR) analysis to combine Glut-1 and EMA, developing a risk score (RS) and performing external validation.
Main Results:
- Individual markers showed good diagnostic performance: Glut-1 (AUC=0.90), EMA (AUC=0.82), Desmin (AUC=0.84).
- A combined RS model using Glut-1 and EMA achieved a higher AUC of 0.93.
- The externally validated RS model demonstrated strong performance with an AUC of 0.91.
Conclusions:
- A risk score (RS) derived from logistic regression of Glut-1 and EMA immunocytochemistry significantly enhances the distinction between MM and RM in effusions.
- The developed RS model is robust, showing high accuracy in external validation, supporting its clinical utility in differential diagnosis.
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.
