Hyperprogression after Anti-Programmed Death-1 Therapy in a Case of Sigmoid Colon Cancer with Lynch Syndrome

INTRODUCTION: Lynch syndrome is a hereditary condition caused by germline defects in mismatch repair (MMR) genes, resulting in microsatellite instability-high (MSI-H) tumors. Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in the treatment of MSI-H advanced cancers. However, hyperprogressive disease (HPD) following ICI therapy is a rare and paradoxical phenomenon. We report a case of advanced sigmoid colon cancer associated with Lynch syndrome that developed HPD after pembrolizumab treatment. CASE PRESENTATION: variant. At 24 months of chemotherapy, the patient remains alive with a sustained partial response. CONCLUSIONS: This case underscores the importance of early response evaluation in ICI-treated MSI-H tumors. Rapid disease progression requires prompt differentiation between HPD and pseudoprogression, emphasizing the necessity of timely therapeutic modification.