Differentiating reactive mesothelial cells from metastatic adenocarcinoma in serous effusions: The utility of immunocytochemical panel in the differential diagnosis

Abstract

Differentiating reactive mesothelial cells (RMs) from metastatic adenocarcinoma cells (MAC) in serous fluids based on cytomorphologic features alone can be very challenging. Various immunocytochemical (ICC) markers have been used to maximize the diagnostic accuracy, however, cytopathologists still encounter difficulties in effusion cytologic diagnosis. The aim of this study was to evaluate previous and recent ICC stains to identify the most sensitive and specific markers and the best panel for differentiating RM from MAC. Cell block sections from 41 MAC and 43 RM effusions cases were subjected to ICC staining for MOC-31, BerEp4, carcinoembryonic antigen (CEA), calretinin, HBME-1, CK5/6, and D2-40. For the MAC cases, the sensitivity of BerEp4, MOC-31, and CEA was 82.9, 92.6, and 17%, respectively, and the specificity was 95.3, 93, and 100%, respectively. For the RM cases, the sensitivity of calretinin, CK5/6, D2-40, and HBME-1 was 95.3, 27.9, 58.1, and 93%, respectively, and the specificity was 70.7, 73.1, 75.6, and 82.9%, respectively. The results show that BerEp4 and MOC-31 are highly sensitive and specific for detecting MAC, whereas calretinin and HBME1 are highly sensitive but only modestly specific for detecting RM cases (P < 0.05). Forced entry logistic regression revealed that using MOC-31, BerEp4, HBME-1, and calretinin, is an excellent panel for making correct diagnosis with 97.6% sensitivity in detecting MAC and 90.7% specificity in detecting RM. We conclude that adding a panel of MOC-31, BerEp4, calretinin, and HBME-1 immunostains to routine cytomorphologic features can greatly enhance the diagnostic accuracy of serous effusions.

Use of the monoclonal antibody MOC‐31 as an immunomarker for detecting metastatic adenocarcinoma in effusion cytology

“…In those studies, MOC-31 was part of a panel of immunohistochemical stains. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] In the current study, the sensitivity (87%) and specificity (100%) of MOC-31 alone in the detection of metastatic adenocarcinoma in effusion cytology specimens was within the range of sensitivities (76%-100%) and specificities (92%-100%) reported for antibody panels that included MOC-31.…”

“…The antibodies currently available for differentiation in effusion specimens include antibodies that recognize cells of mesothelial origin (such as calretinin, D2-40, cytokeratin [CK] 5/6, Wilms' tumor-1 [WT-1], and mesothelin) and antibodies that recognize adenocarcinomas (such as MOC-31, carcinoembryonic antigen [CEA], B72.3, and Ber-Ep4). [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] The majority of studies demonstrating the usefulness of these markers have used panels comprised of different combinations of the antibodies for mesothelial cells/mesothelioma and adenocarcinomas from different primary tumor sites.…”

An improved flow cytometric assay for detection and discrimination between malignant cells and atypical mesothelial cells, in serous cavity effusions

“…Ber-EP4 has been proposed as a highly sensitive (82.9%) and specific (95.3%) marker for detecting metastatic adenocarcinoma cells, contributing to their differentiation from reactive mesothelial cells (9,33,34). The investigation of EMA, CEA (CD66abce), and cytokeratin expression has also been proposed for improving the cytodiagnosis of effusions (2,10,(35)(36)(37)(38).…”

Diagnostic Usefulness of MUC1 and MUC4 for Distinguishing between Metastatic Adenocarcinoma Cells and Reactive Mesothelial Cells in Effusion Cell Blocks

“…Ancillary studies, in particular immunocytochemistry, may be helpful in resolving this dilemma [4]. Various epithelial immunocytochemical markers such as carcinoembryonic antigen (CEA), Ber-Ep4, E-cadherin, and MOC-31 are currently available for differentiating between MAC and RMC [6,8,18,19]. However, a small but significant number of MAC fail to express any of these markers.…”

“…Cell block preparations of effusion fluids provide intact tissue sections for immunocytochemistry [5]. The most commonly used antibodies recognize molecules that are commonly expressed by MAC but are largely absent from RMC; however, a significant number of MAC fail to express any of these markers [6,7,8]. …”