الفهرس 
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Abstract
Malignant mesothelioma is considered a rare aggressive neoplasm with a grave outcome, mostly related to environmental and occupational asbestos exposure. The majority of cases arise from pleural mesothelium while the remainder originate mainly from the peritoneal surface. While rare cases of malignant mesothelioma of pericardium and tunica vaginalis have been documented. Although serosal effusion is the earliest and most common clinical sign reported in malignant mesothelioma patients, the hallmark for diagnosis of malignant mesothelioma is stromal or sub-serosal fat infiltration by malignant mesothelial cells. However, this feature may not be evident as in small tissue specimens. Moreover, the distinction between malignant and benign mesothelial cells based on cytomorphological features can be challenging. Thus, ancillary techniques has a great significance for discrimination between malignant and benign mesothelial proliferation. Numerous immunohistochemical markers have been suggested for distinguishing malignant mesothelial cells. While the early generation of these markers had been reported to exhibit a considerable sensitivity, the specificity of such markers were debated by more recent studies, which emphasized on the significance of markers’ specificity and subsequently, did not recommend the use of these markers for routine diagnosis. MTAP is one of the new generation markers that has shown a significantly high specificity compared with the conventional markers. It has been claimed that the loss of MTAP gene in malignant pleural mesothelioma is frequently associated with the deletion status of 9p21, detected by in-situ hybridization (ISH) technique. Thus, immunohistochemical loss of MTAP staining, particularly the loss of cytoplasmic expression, can indicate homozygous deletion of CDKN2A. EMA is one of the classical early generation markers, which has been reported to have a considerably high sensitivity in differential diagnosis of malignant mesothelioma and reactive mesothelial proliferation. Despite that, it has been recommended to be used as a member of a panel. The current study aimed to investigate and compare the immunohistochemical expression and diagnostic utility of MTAP and EMA in differentiation between malignant mesothelioma and reactive mesothelial proliferation in both tissue biopsies and cell block preparations. The study was carried out on 60 cases of mesothelial lesions, which were divided equally into two groups: epithelioid malignant mesothelioma (EMM) and reactive mesothelial hyperplasia (RMH), and all were of pleural origin. Regarding the epithelioid malignant mesothelioma (EMM) group, 30 cases were included (17 tissue specimens and 13 cell blocks). The mean age was about 70.7 years. Male cases constituted 66.7% of all cases. Regarding reactive mesothelial hyperplasia group (RMH), 30 cases of reactive mesothelial hyperplasia were included (12 tissue specimens and 18 cell blocks). The mean age was 56.07 years. Male and female cases showed nearly equal distribution (16 cases were males and 14 were females). The calculated optimal cut-off point for MTAP that provided the highest sensitivity and specificity for differentiation between EMM and RMH was 52.5% i.e. EMM is diagnosed when 52.5% or more of the mesothelial cells showed loss/decreased MTAP expression. MTAP showed decreased/loss of cytoplasmic immunohistochemical stain in 19 cases of epithelioid malignant mesothelioma (11 tissue specimens and 8 cell blocks), giving a sensitivity of 63.3% (64.7% for tissue specimens and 61.5% for cell blocks). On the other hand, the current study revealed that all of the 30 cases diagnosed with reactive mesothelial proliferation (12 tissue specimens, and 18 cell blocks) retained the cytoplasmic MTAP staining, rendering MTAP a 100% specific marker. EMA showed positive immunohistochemical results in 28 cases of epithelioid malignant mesothelioma (15 tissue specimens and 13 cell blocks), giving a sensitivity of 93.3% (88.2% for tissue specimens and 100% for cell blocks). On the other hand, 10 cases of reactive mesothelial hyperplasia (5 tissue specimens and 5 cell blocks) showed positive immunohistochemical results, giving a specificity of 66.7% (58.3% for tissue specimens and 72.2% for cell block). Within each of the two study groups, the expression of MTAP revealed no statistically significant difference between tissue biopsies and cell blocks, and the same was true in respect of EMA, suggesting that immunocytochemical studies are a fairly reliable surrogate for immunohistochemistry in distinguishing EMM from RMH. The current work is thought to be the first study to examine the relation between the MTAP and EMA expression and the level of agreement between the two markers in distinguishing EMM from RMH, in order to evaluate the diagnostic validity of MTAP/EMA in combination. The current study recorded sensitivity and specificity of MTAP/EMA in combination equal to 97.5% and 66.7%, respectively. Moreover, the recorded sensitivity and specificity of MTAP/EMA in combination regarding tissue biopsies were 95.8% and 58.3%, respectively, while the recorded sensitivity and specificity of MTAP/EMA in combination regarding cell blocks were 100% and 72.2%, respectively, denoting that this combination can enhance the sensitivity for detection of EMM cases.