Case Presentation: Individualizing Treatment for MSI-H Metastatic Pancreatic Cancer in a Patient With Lynch Syndrome
Patient Case:
A 63-year-old patient with a history of right-sided colon cancer treated in 1998 developed a pT1N0 adenocarcinoma arising in a transverse colon polyp in 2011, leading to a diagnosis of Lynch syndrome. In February 2022, imaging identified a pancreatic head mass with an associated retrocrural para-aortic lymph node. Endoscopic ultrasound-guided biopsy demonstrated poorly differentiated adenocarcinoma consistent with a pancreatic primary. CA 19-9 was within the normal range.
The patient received preoperative FOLFIRINOX from April through October 2022. Initial imaging showed a reduction in retrocrural lymphadenopathy. In November 2022, he underwent pancreaticoduodenectomy with tangential resection of the superior mesenteric vein. Pathology revealed a grade 3 carcinoma with medullary features, staged as ypT3N2.
Postoperative imaging revealed multiple FDG-avid liver lesions concerning for metastatic disease, and gemcitabine plus nab-paclitaxel was initiated in February 2023. Molecular testing of the pancreatic tumor demonstrated loss of MSH2 and MSH6 expression and microsatellite instability-high (MSI-H) disease, with instability at all 5 tested loci. Comprehensive tumor profiling also identified a high tumor mutational burden of 51.1 mutations/Mb and a somatic BRCA2 mutation. Further genetic testing excluded germline BRCA1 and BRCA2 mutations.
Subsequent imaging demonstrated progressive hepatic metastases and recurrent disease in the celiac region. Given his previously treated MSI-H metastatic pancreatic cancer, the patient initiated pembrolizumab in June 2023.
The patient achieved a deep and durable response to immune checkpoint blockade, with serial imaging showing progressive reduction of the hepatic metastases and periceliac recurrence. By June 2025, the previously intense FDG uptake in the celiac region had markedly decreased and was no longer clearly appreciable. The FDG-avid liver lesion was also no longer clearly visualized.
More than 3 years after initiating immunotherapy, the patient remains in excellent clinical condition with an ECOG performance status of 0. CT imaging in June 2026 showed a further minimal reduction in the residual right hepatic abnormality without evidence of pancreatic cancer progression. CA 19-9 remained within the normal range at 6.5 U/mL.
