The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study.
ABSTRACT As both mesotheliomas and squamous carcinomas can present a wide variety of morphological patterns, they can on occasion be confused. Recently, some groups of investigators have called attention to the difficulties that sometimes exist in distinguishing between these malignancies and the need to define a panel of markers that can assist in reaching the correct diagnosis. The aim of the present study is to compare the value of the various immunohistochemical markers currently available for the diagnosis of mesothelioma and squamous carcinoma of the lung. A total of 30 epithelioid pleural mesotheliomas exhibiting a solid or predominantly solid pattern, and 30 nonkeratinizing squamous carcinomas of the lung were investigated for the expression of the following markers: podoplanin, calretinin, mesothelin, WT1, keratin 5/6, keratin 7, p63, carcinoembryonic antigen (CEA), MOC-31, Ber-EP4, B72.3, BG-8 (Lewis(y)), leu-M1 (CD15), and thyroid transcription factor-1 (TTF-1). All 30 (100%) of the mesotheliomas reacted for calretinin, mesothelin and keratin 7, 93% each for podoplanin, WT1 and keratin 5/6, 13% for Ber-EP4, 7% each for p63, MOC-31 and BG-8, and 0% for B72.3, CEA, leu-M1 and TTF-1. All 30 (100%) of the squamous carcinomas were positive for p63 and keratin 5/6, 97% for MOC-31, 87% for Ber-EP4, 80% for BG-8, 77% for CEA, 57% for keratin 7, 40% for calretinin and B72.3, 30% for leu-M1, 27% for mesothelin, 15% for podoplanin, and 0% for WT 1 and TTF-1. After analyzing the results, it is concluded that from a practical point-of-view, a combination of two positive mesothelioma markers (WT1 and calretinin or mesothelin) with two negative mesothelioma markers (p63 and MOC-31) would allow the differential diagnosis to be established between epithelioid mesotheliomas and squamous carcinomas of the lung in nearly all instances.
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ABSTRACT: Adenocarcinoma can be challenging to distinguish from malignant mesothelioma in effusions, and this distinction often requires ancillary studies and clinical correlation. Immunohistochemistry for claudin-4, a tight-junction-associated protein, has recently been shown to distinguish adenocarcinoma from malignant mesothelioma, mostly in surgical specimens. Our aim was to validate and assess the immunoreactivity profile of claudin-4 in a large series of malignant effusions. We evaluated 159 malignant effusions (84 adenocarcinomas and 75 malignant mesotheliomas). Claudin-4 immunohistochemistry was performed on cell-block paraffin sections and scored for staining intensity, staining pattern (cytoplasmic versus membranous), and percentage of positive tumor cells. Appropriate positive and negative controls were used throughout. All cases of mesothelioma were negative for claudin-4 (0 of 64). Eighty-three of 84 cases of adenocarcinoma were positive (99%); 1 case of serous carcinoma was negative. Most adenocarcinomas showed strong and diffuse membranous staining (71 of 84; 84%); 12 cases (14%) showed membranous staining of moderate intensity. The overall sensitivity for adenocarcinoma was 99% (83 of 84). Claudin-4 immunohistochemistry effectively distinguishes adenocarcinoma from malignant mesothelioma with high sensitivity and specificity in the evaluation of malignant effusions. Cancer (Cancer Cytopathol) 2013. © 2013 American Cancer Society.Cancer Cytopathology 01/2014; · 4.43 Impact Factor
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ABSTRACT: Epithelioid mesotheliomas and breast carcinomas can present a variety of morphologic patterns. Because of this, breast carcinomas that metastasize to the pleura and lung may be confused with mesotheliomas. The aim of the present study is to compare the immunohistochemical markers currently available for the diagnosis of these two malignancies, and to determine the best panel of markers that can be used to assist in discriminating between them. Sixty epithelioid mesotheliomas and 80 breast carcinomas [40 triple-negative and 40 estrogen receptor (ER)-positive] were investigated for expression of the positive mesothelioma markers calretinin, keratin 5/6, mesothelin, podoplanin, thrombomodulin and WT1, the positive carcinoma marker claudin-4, and the breast-associated markers gross cystic disease fluid protein-15 (GCDFP-15), mammaglobin and GATA3. All of the epithelioid mesotheliomas reacted for calretinin and keratin 5/6, 93% for WT1, 88% for podoplanin, 77% for thrombomodulin, 23% for GATA3, and 0% for claudin-4, GCDFP-15 and mammaglobin, respectively. Of the triple-negative breast carcinomas, 100% expressed claudin-4, 5% keratin 5/6, 30% GATA3, 18% mammaglobin, 15% GCDFP-15, 56% mesothelin, 38% calretinin, 18% thrombomodulin, 5% WT1, and 3% podoplanin. Among the ER-positive breast carcinomas, 100% were claudin-4 and GATA3 positive, 70% expressed GCDFP-15, 63% mammaglobin, 13% calretinin, 13% thrombomodulin, 8% WT1, 5% keratin 5/6, 3% mesothelin, and 0% podoplanin. It is concluded that podoplanin and WT1 are the best positive mesothelioma markers for differentiating epithelioid mesotheliomas from breast carcinomas. An accurate differential diagnosis can be reached with the use of these two markers in combination with the breast-associated markers GCDFP-15, mammaglobin, and GATA3.Human pathology 07/2014; · 2.81 Impact Factor
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ABSTRACT: Histologic distinction among non-small cell lung carcinomas, particularly between squamous cell carcinoma (SQC) and adenocarcinoma (ADC), has become more important. Recently, a p40 antibody was suggested to be a highly specific marker for SQC. We evaluated p40 expression and compared it with the expression of other SQC markers in 580 primary lung carcinomas, including 158 SQCs, 156 ADCs, 50 carcinoid tomors, 107 large cell neuroendocrine carcinomas, 68 small cell lung carcinomas, and 41 malignant mesotheliomas. Detailed histologic distributions of p40-positive cases were as follows: 153 (96.8%) of 158 SQCs, 7 (4.6%) of 152 ADCs, 0 (0%) of 50 carcinoid tomors, 4 (3.6%) of 107 large cell neuroendocrine carcinomas, 1 (1.5%) of 68 small cell lung carcinomas, and 1 (2.4%) of 41 mesotheliomas. p40 staining yields high sensitivity as well as high specificity for distinguishing SQC from ADC, neuroendocrine carcinomas, and malignant mesothelioma.Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 22(5):377-382. · 1.63 Impact Factor