Molecular testing of cytology specimens: Issues in specimen adequacy and clinical utility

Next generation sequencing (NGS) is standard of care for workup of many neoplasms including adenocarcinomas of the lung. Molecular testing of cytology samples is used for many types of neoplasms but the value of such testing for the selection of "first"- and "second-line" treatment protocols is incompletely understood.

Fifty-six sequentially performed cytology specimens (49 fine needle aspirates and 7 fluids) submitted for molecular analysis were reviewed by a medical oncologist to determine specimen adequacy and utility of results for therapy selection. Chart review was performed to determine availability of microsatellite instability status, tumor mutational burden, and presence of driver mutations treatable with targeted therapy in a "first"- or "second-line" application.

Forty of 56 cases were successfully sequenced and 34% (19/56) had targetable mutations detected by NGS. Ten of these 19 cases (53%) received targeted therapy for their tumor type with five of 10 patients receiving "first-line" therapy and five (50%) "second-line" therapy. Twenty-two mutations were detected where no targeted therapy for the patient's tumor type existed but targeted therapies were available for other tumor types. Of these specimens, only one patient received treatment using protocols associated with a second tumor type. Total mutation burden and microsatellite instability status results were obtained in 29 of 56 cases (52%).

71% (40/56) of cytologic specimens were adequate for sequencing with 34% (19/56) demonstrating a targetable mutation and 53% of these patients receiving therapy targeted to the driver mutation of their tumor type.