Frequent expression of conventional endothelial markers in pleural mesothelioma: usefulness of claudin-5 as well as combined traditional markers to distinguish mesothelioma from angiosarcoma

•Some sarcomas express keratin, complicating their differentiation from mesothelioma.•Mesothelioma sometimes expresses endothelial markers.•Angiosarcomas expressing keratin resemble sarcomatoid mesotheliomas.•Claudin-5 is useful to discriminate angiosarcoma from mesothelioma. Distinguishing pleural...

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Published in:Lung cancer (Amsterdam, Netherlands) Netherlands), 2020-10, Vol.148, p.20-27
Main Authors: Nakashima, Yasuhiro, Inamura, Kentaro, Ninomiya, Hironori, Okumura, Sakae, Mun, Mingyon, Kirimura, Susumu, Kobayashi, Masashi, Okubo, Kenichi, Ishikawa, Yuichi
Format: Article
Language:English
Subjects:
angiosarcoma
Biomarkers, Tumor
Claudin-5
Diagnosis, Differential
Hemangiosarcoma - diagnosis
Humans
immunohistochemistry
Lung Neoplasms - diagnosis
Mesothelioma - diagnosis
Pleural mesothelioma
Pleural Neoplasms - diagnosis
sarcomatoid mesothelioma
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Summary:•Some sarcomas express keratin, complicating their differentiation from mesothelioma.•Mesothelioma sometimes expresses endothelial markers.•Angiosarcomas expressing keratin resemble sarcomatoid mesotheliomas.•Claudin-5 is useful to discriminate angiosarcoma from mesothelioma. Distinguishing pleural sarcomatoid mesotheliomas from true sarcomas is challenging because the former does not always express the mesothelial markers, and diagnosis is often made on the basis of keratin expression. Consequently, sarcomas such as angiosarcomas that express keratin complicate the differential diagnosis. Furthermore, some mesotheliomas have been reported to express endothelial markers. The aim of this study is to identify useful markers for distinguishing pleural sarcomatoid mesothelioma from angiosarcoma. This study enrolled 147 patients with pleural mesothelioma—93 with epithelioid, 25 with biphasic, and 29 with sarcomatoid subtypes—and 41 patients with angiosarcomas in various organs. The expression levels of cytokeratin, mesothelial, and endothelial markers were assayed in both groups to identify the markers that could assist in distinguishing mesothelioma from angiosarcoma. Cytokeratin (AE1/AE3, CAM 5.2), endothelial (CD31, CD34, ERG, factor VIII, and claudin-5), and mesothelial (calretinin, WT-1, podoplanin (D2-40), EMA, and CK5/6) markers were immunohistochemically assayed using tissue blocks. More than 90% of the mesotheliomas and less than 20% of the angiosarcomas expressed cytokeratin. Calretinin was expressed in 82% of all types of mesotheliomas but in only 48% of sarcomatoid mesotheliomas. Endothelial markers were expressed in mesothelioma tissues—CD31 in 10.3%, CD34 in 3.5%, ERG in 29%, and factor VIII in 3.4%—and the positivity was higher in sarcomatoid than in epithelioid and biphasic mesotheliomas. Claudin-5 was expressed in all the angiosarcomas, but not in any of the mesotheliomas. We found overlapping immunophenotypes in pleural mesotheliomas and angiosarcomas, but the sensitivity and specificity of claudin-5 expression were sufficient to distinguish between them. The differential diagnosis of mesothelioma should therefore include claudin-5 in a panel of immunohistochemical markers to distinguish mesothelioma from angiosarcoma.
ISSN:0169-5002
1872-8332
DOI:10.1016/j.lungcan.2020.07.029