Immune Checkpoint Inhibition as a Novel Strategy for Microsatellite Instability-High Duodenal Adenocarcinoma: A Report of Three Cases.

INTRODUCTION

Duodenal adenocarcinoma (DA) is an extremely rare malignancy, accounting for less than 1% of all gastrointestinal cancers. Most cases are diagnosed at an advanced stage, making curative resection difficult and leading to a poor prognosis. Recent advances in tumor immunology have identified microsatellite instability-high (MSI-H) and deficient mismatch repair (dMMR) as predictive biomarkers for immune checkpoint inhibitors (ICIs). However, clinical evidence regarding their efficacy in DA remains limited. We report 3 cases of MSI-H/dMMR DA.

CASE PRESENTATION: (a) Case 1: A 55-year-old woman underwent pancreaticoduodenectomy for DA and was subsequently diagnosed with Lynch syndrome. She has remained recurrence-free for 5 years and 2 months postoperatively. (b) Case 2: A 75-year-old man with locally advanced DA and impaired oral intake declined pancreaticoduodenectomy. After gastrojejunostomy, pembrolizumab was administered, achieving durable disease control for 1 year and 10 months. (c) Case 3: A 65-year-old woman with DA invading adjacent organs received neoadjuvant pembrolizumab. Following bowel obstruction, she underwent partial small intestine resection, and pathological examination revealed a complete response. She has remained recurrence-free for 3 years and 2 months.

CONCLUSIONS

Surgical resection remains the standard treatment for DA. However, in MSI-H/dMMR cases, ICIs are expected to be effective, as observed in other gastrointestinal cancers. Pembrolizumab may represent a useful neoadjuvant option, and in patients who achieve a pathological response, nonsurgical management could also be considered.