الفهرس 
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Abstract
Cytologic examination of serous membrane effusion is an essential diagnostic modality in differentiating malignant from benign effusions. We aimed to assess if the sensitivity of malignancy detection would improve by preparation of CB from the effusion fluid in addition to the conventional smear. We also evaluated the diagnostic value of claudin-4, MOC-31 and EZH2 IHC in differentiating between MC, malignant mesothelioma, and RMCs in effusion samples. This study included 190 cases of serous effusion (pleural, peritoneal and pericardial). One half of each specimen was used for smear preparation, while the other half was used for CB preparation. Smear and CB of each case were separately examined and categorized according to TIS recommendations, then, the final cytologic diagnosis was assigned for each case by combination of smear and CB results. For IHC, 90 (32 benign with RMC, 55 MC and 3 mesotheliomas) cases of serous effusions were included. Immunostaining using claudin-4, MOC-31 and EZH2 was performed on CB sections of these cases. Assessment of staining patterns, intensity and percentage of target cells stained was done. According to combined smear and CB results, the study cases were distributed to TIS categories as follows: 3.2% ND, 62.1% NFM, 2.6% AUS, 4.2% SFM, and 27.9% MAL. The rate of ND, AUS and SFM categories showed stepwise reduction from smear to CB to the combination of both with concomitant increase in the rates of NFM and MAL. When both SFM and MAL were considered positive, the combination of smear and CB increased the sensitivity of malignancy detection by 13.34% as compared to smear alone. Considering IHC, claudin-4 showed membranous staining in 53/55 of MC and 1/32 of RMC, while MOC-31 was positive in 49/55 of MC and 2/32 of RMC. High EZH2 (≥ 50% of target cells) was detected in 47/55 MC and 2/32 RMC. All three mesothelioma cases were negative for claudin-4 and MOC-31 and showed high EZH2 expression. For the discrimination between MC and RMC, the sensitivity and specificity were 96.4% & 96.9% for claudin-4, 89.1% & 93.8% for MOC-31 and 85.45% & 93.75% for high EZH2. The combination of claudin- 4 and high EZH2 showed 100% sensitivity and 90.6% specificity, and the combination of MOC-31 and high EZH2 showed 98.2% sensitivity and 93.8% specificity. The International System (TIS) for reporting serous fluid cytopathology is an easy and reproducible system that provides clear definition of different categories, thus facilitates comparison between studies. Cell block increases the sensitivity, specificity and diagnostic accuracy of cytologic examination of serous effusions when used as an adjunct to conventional smears. It provides higher accuracy of tumor typing due to better morphologic preservation than smear. Moreover, it provides several serial sections that can be used for IHC. The cell block preparation method using alcohol-formalin as a fixative is simple, efficient and reproducible method. Claudin-4 shows high sensitivity and specificity and is superior to MOC-31 in differentiation between MC and RMC in effusion cytology. High EZH2 expression shows high specificity and moderate sensitivity for MC. The combinations of claudin-4 or MOC-31 and high-EZH2 would increase the sensitivity. However, the use of EZH2 is of limited value due to its focal expression in RMC and inflammatory cells. TIS is recommended to be used in reporting of serous fluid samples for more standardized data and better communication with clinicians. In addition to conventional smears, cell blocks should be routinely prepared from effusion cytology samples for better diagnostic accuracy and availability of material for further studies. Claudin-4 might be useful as a solitary marker for MC in effusion samples with high sensitivity and specificity. Further studies are recommended to confirm the diagnostic value of the combinations of claudin-4 or MOC-31 and high- EZH2, evaluating both the benefits and the difficulties of interpretation. Further researches including more cases of mesothelioma are recommended to evaluate the utility of claudin-4, MOC-31 and high EZH2 in differentiation between mesothelioma and RMC, or mesothelioma and MC in effusion samples.