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This review aims to provide useful approaches with which to resolve key difficulties in cytologic diagnosis through the use of ancillary studies, focusing on immunohistochemistry. These approaches are suggested in concert with clinical, radiographic, and morphologic findings. The differentiation of reactive mesothelial cells from malignant mesothelioma and adenocarcinoma is a recurring theme, and Wilms tumor 1 (WT1)\/AE1\/AE3, claudin 4, and BRCA1\u2010associated protein 1 (BAP1) immunostains are useful new tools in the armamentarium. A targeted workup is suggested for patients with no known primary site or with multiple prior malignancies. Molecular and other biomarker testing can be performed on even modestly cellular fluid specimens and may allow patients to benefit from targeted therapy without the need for additional tissue biopsies.\n                    <jats:bold>\n                      <jats:italic>Cancer Cytopathol<\/jats:italic>\n                      2018;000:000\u2010000.\n                    <\/jats:bold>\n                    \u00a9\n                    <jats:italic>2018 American Cancer Society.<\/jats:italic>\n                  <\/jats:p>","DOI":"10.1002\/cncy.22021","type":"journal-article","created":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T05:03:33Z","timestamp":1535605413000},"page":"590-598","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Ancillary studies in pleural, pericardial, and peritoneal effusion 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