The use of epithelial membrane antigen and silver-stained nucleolar organizer regions testing in the differential diagnosis of mesothelioma from benign reactive mesothelioses

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Abstract
BACKGROUND The accurate diagnosis of pleural lesions obtained from small closed biopsy is difficult. As yet there is no single reliable test to distinguish between malignant and benign mesothelial tissue. METHODS Immunostaining of epithelial membrane antigen (EMA) and the quantitation of silver stained nucleolar organizer regions (AgNORs) each were applied to benign and malignant histologic sections of pleural and peritoneal biopsies. The usefulness of these stains was tested both individually and in combination in the diagnosis of epithelial malignant mesothelioma. RESULTS One hundred and three of the 141 malignant lesions (73%) were immunoreactive for EMA but only 3 of the 73 benign lesions (4%) reacted equivocally, and none positively. The average count of AgNORs/cell in malignant lesions (n = 80) was elevated compared with benign cases (n = 26), but a significant overlap was exhibited in the AgNOR count and this form of analysis was considered to be of little value in distinguishing benign from malignant mesothelial processes. Much less overlap was observed when the average AgNOR area was measured. By using the maximum benign AgNOR area of 0.6677 μm2 as the upper threshold, 51 cases (63.8%) were identified as malignant; the test demonstrated 100% specificity and 63.8% sensitivity. By combining the EMA and AgNOR results, 76 of 80 of the malignant mesothelioma cases (95%) tested positive for at least 1 of the tests with no false‐positive results identified. CONCLUSIONS This study confirms the usefulness of EMA in diagnosing malignant and benign mesothelial lesions, and demonstrates the enhanced diagnostic value of combining EMA immunoreaction with the average area of AgNOR per cell, thereby increasing sensitivity in the diagnosis of epithelial malignant mesothelioma. Cancer 1998;82:583‐90. © 1998 American Cancer Society.