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: Liquid CDx analysis detected a high circulating tumor DNA fraction but reported the tumor as microsatellite stable, highlighting a discordance in MSI classification across platforms. Given her favorable clinical condition and emerging molecular findings, pembrolizumab was initiated. The patient experienced sustained clinical benefit and radiographic stability for 13 months before progressing with peritoneal carcinomatosis and ascites. 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.