Cyst fluid: add NGS
A recent discussion recommended adding NGS alongside standard cyst fluid tests (CEA, amylase) to detect driver mutations in otherwise nondiagnostic aspirates — a practical workflow tip for FNA clinics. The thread underscored NGS’s value in converting nondiagnostic cyst fluid into actionable molecular information. (x.com/ACGCRJ/status/2038334598879297867)
A 2017–2018 prospective cohort of 626 pancreatic cyst fluid specimens found preoperative detection of KRAS and/or GNAS by targeted NGS had 100% sensitivity and 96% specificity for identifying IPMN among 102 surgically verified cases, and combining KRAS/GNAS with TP53/PIK3CA/PTEN alterations reached 89% sensitivity for advanced neoplasia. (gut.bmj.com) The PancreaSeq Genomic Classifier is a DNA+RNA, targeted NGS assay used in multicenter validation ( >1,800 patients across 31 U.S. centers), runs on a 74‑gene platform, and reports a genomic risk algorithm with an analytic turnaround time typically listed as 7–14 days. (pancreaseq.com) UPMC/ PancreaSeq collection instructions specify 200–600 µL of cyst fluid added to a 600 µL stabilizing reagent (guanidinium thiocyanate), with room‑temperature stability <3 hours, refrigeration allowed up to 24 hours, and freezing for long‑term storage prior to overnight shipment (ship Mon–Thu to the reference lab). (pancreaseq.com) Multiple studies show diagnostic DNA can come from cell‑free DNA in acellular or paucicellular cyst aspirates, allowing NGS to yield driver mutations where cytology is nondiagnostic; Scientific Reports and other cohorts demonstrated that targeted NGS on cyst fluid increased overall diagnostic accuracy versus cytology alone. (nature.com) Combining molecular NGS results with standard biomarkers improves performance metrics: one series reported KRAS/GNAS NGS sensitivity 53% and specificity 92% for mucinous cysts, with a combined NGS+CEA strategy increasing sensitivity to 78% and specificity to 87% in that cohort. (sciencedirect.com) Billing and policy context: a proprietary PLA CPT code (0313U) exists for the PancreaSeq Genomic Classifier, but multiple payer policies still designate cytology plus CEA and amylase as the first‑line, medically‑necessary cyst fluid tests and may consider molecular classifiers investigational or subject to coverage limits. (aapc.com) Operational takeaway supported by reference protocols: most reference labs require an accompanying endoscopy/cytology report with the NGS send‑out, recommend dedicated collection vials/kits to meet minimum volume and preservative requirements, and note specimen handling (freeze on receipt, ship fast) to avoid failed runs from low DNA yield. (nordx.testcatalog.org)
