Case report: immunotherapy response in pancreatic cancer after MSI-H emerged post-chemotherapy.

Background: Microsatellite instability-high (MSI-H) is an established biomarker of response to immune checkpoint inhibitors, though it is rarely observed in pancreatic ductal adenocarcinoma (PDAC). Even less common is the emergence of MSI-H during the disease course, particularly when identified through liquid biopsy. Such findings raise important considerations regarding tumor evolution, assay concordance, and therapeutic decision-making. Case Presentation: We report the case of a 76-year-old woman with borderline resectable PDAC who received first-line chemotherapy for nearly 20 months, maintaining excellent performance status and disease control. Upon clinical and biochemical progression, liquid biopsy using Guardant360 CDx revealed MSI-H status and a TP53 H214fs mutation, both absent in her initial molecular profile. A concurrent FoundationOne Conclusions: This case illustrates the potential emergence of MSI-H during the disease course of PDAC and highlights the clinical value of repeat molecular profiling at progression. It also highlights clinically relevant discrepancies in MSI detection between liquid biopsy platforms and supports the role of immunotherapy in selected patients with evolving molecular features.