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The versatility of cytology specimen preparations has provided ample opportunity for the cytopathology community to evolve, innovate and \u2018do more with less\u2019 using limited amounts of tissue. More recently, cytology\u2010derived supernatant liquid biopsy samples have been identified as a substantial source of high\u2010quality genomic material that can be interrogated for genotyping for therapeutic decision\u2010making, as well as other roles in cancer screening for early\u2010stage disease, longitudinal monitoring for therapeutic response and disease prognostication. These novel substrates, including supernatants from body fluids such as urine, pleural effusion, ascitic fluid, cerebrospinal fluid, as well as fine\u2010needle aspiration (FNA) specimens, serve as a bridge between tissue\u2010based testing and conventional liquid biopsy testing from the patient's plasma. Cytologically derived liquid biopsy samples can only be used in\u00a0situations where the tissue sample is inadequate for genotyping, or when plasma\u2010based liquid biopsy fails to identify an oncogenic driver alteration, but they can be used as a stand\u2010alone complementary specimen source that can provide reliable genomic information for therapeutic decisions. This review aims to highlight some of the advances in the field and the clinical applications of the cytology\u2010derived supernatant specimen.<\/jats:p>","DOI":"10.1111\/cyt.13475","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T10:05:38Z","timestamp":1739268338000},"page":"222-227","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Bridge: Supernatant Derived From Cytological Sample Preparations"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9447-7701","authenticated-orcid":false,"given":"Sinchita","family":"Roy\u2010Chowdhuri","sequence":"first","affiliation":[{"name":"Division of Pathology and Laboratory Medicine, Department of Pathology MD Anderson Cancer Center, The University of Texas  Houston Texas 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