Cytological differential diagnosis among adenocarcinoma, epithelial mesothelioma, and reactive mesothelial cells in serous effusions by immunocytochemistry

Su, Xueying; Li, Gan-di; Liu, Weiping; Xie, Chengxia; Jiang, Chen

doi:10.1002/dc.21489

Cited by 68 publications

(103 citation statements)

References 29 publications

(29 reference statements)

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“…65 Immunohistochemical markers used on histological samples to differentiate between benign and malignant mesothelial proliferation have also been used in cytology with similar unsatisfactory results. [28][29][30][31][32][33][34][35][36] The present study shows that the BAP1 profile of mesothelial cells is also easily identifiable on effusions and cell blocks. Benign mesothelial cells were invariably positive for BAP1, whereas 64% of mesotheliomas showed loss of protein; in equivocal cases by morphology, BAP1 negativity on mesothelial cells had a 100% positive predictive value for the diagnosis of mesothelioma: all six samples containing mesothelial cells negative for BAP1 were associated with a histological diagnosis of BAP1-negative mesothelioma.…”

Section: Discussionsupporting

confidence: 60%

BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations

et al. 2015

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The distinction between malignant mesothelioma and reactive mesothelial proliferation can be challenging both on histology and cytology. Recently, variants of the BRCA1-associated protein 1 (BAP1) gene resulting in nuclear protein loss were reported in hereditary and sporadic mesothelioma. Using immunohistochemistry, we evaluated the utility of BAP1 expression in the differential diagnosis between mesothelioma and other mesothelial proliferations on a large series of biopsies that included 212 mesotheliomas, 12 benign mesothelial tumors, and 42 reactive mesothelial proliferations. BAP1 stain was also performed in 70 cytological samples (45 mesotheliomas and 25 reactive mesothelial proliferations). BAP1 was expressed in all benign mesothelial tumors, whereas 139/212 (66%) mesotheliomas were BAP1 negative, especially in epithelioid/biphasic compared with sarcomatoid/desmoplastic subtypes (69% vs 15%). BAP1 loss was homogeneous in neoplastic cells except for two epithelioid mesotheliomas showing tumor heterogeneity. By fluorescence in situ hybridization, BAP1 protein loss was paralleled by homozygous deletion of the BAP1 locus in the vast majority of BAP1-negative tumors (31/41, 76%), whereas 9/10 BAP1-positive mesotheliomas were normal. In biopsies interpreted as reactive mesothelial proliferation BAP1 loss was 100% predictive of malignancy, as all 6 cases subsequently developed BAP1-negative mesothelioma, whereas only 3/36 (8%) BAP1-positive cases progressed to mesothelioma. On cytology/cell blocks, benign mesothelial cells were invariably positive for BAP1, whereas 64% of mesotheliomas showed loss of protein; all 6 cases showing BAP1 negativity were associated with histological diagnosis of BAP1-negative mesothelioma. BAP1 stain also showed utility in the differential of mesothelioma from most common pleural and peritoneal mimickers, such as lung and ovary carcinomas, with specificity and sensitivity of 99/70% and 100/70%, respectively. Our results show that BAP1 protein is frequently lost in mesothelioma, especially of epithelioid/biphasic subtype and is commonly associated with homozygous BAP1 deletion. BAP1 immunostain represents an excellent biomarker with an unprecedented specificity (100%) in the distinction between benign and malignant mesothelial proliferations. Finding BAP1 loss in mesothelial cells should prompt to immediately reevaluate the patient; moreover, it might be useful in mapping tumor extent and planning surgical resection.

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Section: Discussionsupporting

confidence: 60%

BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations

et al. 2015

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“…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.…”

Section: -3mentioning

confidence: 51%

“…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.…”

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confidence: 99%

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

Kundu

Krishnamurthy

2011

Cancer Cytopathology

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BACKGROUND:MOC‐31 is an established immunologic marker with which to detect adenocarcinomas. The objective of the current study was to evaluate the use of MOC‐31 in the diagnosis of metastatic adenocarcinoma in effusion specimens.METHODS:The authors evaluated cytologic specimens of effusions/washings in which MOC‐31 immunostaining was performed on unstained cell block sections or Papanicolaou‐stained cytospin preparations. Membranous staining with or without cytoplasmic staining was considered to be positive. The immunostaining results were correlated with the cytologic diagnoses and clinical follow‐up data.RESULTS:A total of 215 effusions and washings were identified (cell blocks in 162 cases, cytospin preparations in 53 cases, and both in 2 cases in which MOC‐31 immunostaining was performed). A total of 94 (44%) of the 215 cases were found to be positive for malignancy, including 87 metastatic adenocarcinomas. Specimens were positive for MOC‐31 in 76 (87%; 55 cell blocks and 21 cytospin preparations) of 87 cases of metastatic adenocarcinoma. Eleven cases of metastatic adenocarcinoma were found to be negative for MOC‐31 (4 cases from lung tumors, 2 from stomach tumors, 2 from colon tumors, 2 from breast tumors, and 1 from a renal tumor). Minimal and/or focal cytoplasmic staining for MOC‐31 was noted in 13% of cases of reactive mesothelial cells/mesothelioma. The sensitivity of MOC‐31 for metastatic adenocarcinoma was 89%, the specificity was 100%, the negative predictive value was 92%, and the positive predictive value was 100%.CONCLUSIONS:MOC‐31 alone was found to be highly sensitive for distinguishing reactive mesothelial cells/mesothelioma from metastatic adenocarcinoma in effusion specimens. Interpreting membranous MOC‐31 staining as positive can help prevent confusion between reactive mesothelial cells/mesothelioma and metastatic adenocarcinoma. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society

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“…Cotton block method is another alternative by which cytomorphological features in body fluids can be studied. 11,[15][16][17] In this study, all three malignancies found in the smears and blocks were adenocarcinomas. This comprised 8.1 % of cases (3/37).…”

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confidence: 48%

Comparison of the diagnostic accuracy of cell block with cytology smear in serous effusions

Bista

2013

J Pathol Nep

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Background: Differentiation between benign and malignant serous effusions always poses a great diagnostic dilemma. Differentiation often requires clinical findings, morphological evaluation and sometimes immunocytochemistry. Diagnostic possibility is enhanced if cell blocks are made along with the conventional cytology smears. This will help the clinicians in both treating the patient and determining the outcome of the disease process. Materials and methods:This hospital-based cross sectional analytical study was carried out in Department of Pathology in National Academy of Medical Sciences, Bir Hospital for one year. The objective of this study was to compare the smears cytology with cell blocks sections in serous effusions. Results:The four criteria scored for each technique were volume of background blood, amount of diagnostic cellular material, degree of cellular degeneration and trauma and architectural preservation. Background blood, amount of diagnostic material present and retention of architecture was more in cell block sections compared with smears cytology; whereas cellular degeneration and trauma was less appreciated in cell block sections which scored more than the smears cytology. Conclusion:Cell block preparation is simple, rapid and inexpensive technique for serous fluids in which malignant cells can be reliably detected thus avoiding unnecessary invasive procedure in patient management.

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Cytological differential diagnosis among adenocarcinoma, epithelial mesothelioma, and reactive mesothelial cells in serous effusions by immunocytochemistry

Cited by 68 publications

References 29 publications

BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations

BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations

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

Comparison of the diagnostic accuracy of cell block with cytology smear in serous effusions

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