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Reliability Of P-16, Calretinin, And Claudin-4 Immunocytochemistry In Diagnostic Verification Of Effusion Cytology

E. Abusinna, S. Tabak, Yasmine F Elesawy
Published 2019 ·

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© 2019 Egyptian Journal of Pathology | Published by Wo Background The overlapping phenotypic features between the reactivemesothelial cells and the malignant ones pose a major diagnostic challenge in routine cytology practice. Questions have been raised about the privilege of cell block (CB) over conventional smears. There is a lot of controversy about the best immunohistochemical panel that could help in differentiation. Aim This research attempts to compare between the cellular morphology results in conventional smears and CB method. It seeks to address the reliability of calretinin, p-16, and claudin (CL)-4 immunohistochemistry use as an aid to differentiate between reactive and malignant mesothelial cells as well as carcinomatous ones in serous effusion samples. Materials and methods Thisretrospectivestudywasconductedon46(23pleuraleffusionand23peritonealone) cases of effusion fluids. Conventional smears and paraffin-embedded blocks sections were examined and score tabulated. Calretinin, p-16, and CL-4 immunohistochemical expression was studied and correlated with available clinical and cytological data. Results Of the 46 cases studied, therewere 25 (54.3%) cases ofmetastatic adenocarcinoma, 10 (21.7%) cases of mesothelioma, and 11 (23.9%) cases of reactive effusions. Our studied cases showed that 24/46 (52.2%) CBs had cytomorphologic criteria of the diagnostically superior group compared with 22/46 (47.8%) smears. The group of diagnostically adequate material was represented by 22/46 (47.8%) CBs and 24/46 (52.2%)smears.Considering calretinin immunocytochemistry, regardingdetectionof mesothelial cell lesions, sensitivity was 52.4%, specificity was 100%, positive predictive value was 100%, negative predictive value was 71.4%, and total accuracy was 78.26%. p-16 as a differentiating marker between mesothelioma and atypical reactive mesothelial cells has a sensitivity of 45.5%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 62.5%, and total accuracy of 71.43%. CL-4 being a marker of metastatic adenocarcinoma was used to differentiate it frommesothelioma; CL-4 has 96% sensitivity, 60% specificity, 85.7% positive predictive value (PPV), 85.7% negative predictive value (NPV), and total accuracy of 85.7%. When a panel of two markers was assessed as an ancillary technique to cytomorphology, the combination of calretinin negativity and CL-4 positivity had the best results in diagnosing cases of metastatic adenocarcinoma with 96% sensitivity, 80.9% specificity, and 89.1% total accuracy. A panel of three markers was applied to differentiate benign from malignant effusions and for subclassifying malignant ones into mesotheliomatous versus metastatic. Regarding benign reactive effusions, the studied panel had a sensitivity of 27.3%, a specificity of 100%, and total accuracy of 82.6%. Considering mesothelioma cases, the panel has 30% sensitivity, 88.9% specificity, and 76.1% accuracy. When the panel was applied to detect metastatic cases, it revealed 44% sensitivity, 85.7% specificity, and 63% total accuracy. Conclusion The findings of this study suggest that CB use is an added privilege in serous effusion cytology. Immunohistochemical panel of calretinin, p-16, and CL-4 is beneficial in differentiating benign from malignant effusions and for subclassifying malignant ones into mesotheliomatous versus metastatic.
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