Harnessing immunotherapy in sporadic MSI-H/dMMR colorectal cancer: a case study

Colorectal cancer (CRC) is a prevalent malignancy, with microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumors representing a distinct, immunogenic subset. These tumors respond poorly to conventional chemotherapy but demonstrate favorable outcomes with immune checkpoint inhibitors (ICIs). We report the case of a 90-year-old male with severe anemia and a newly diagnosed sporadic MSI-H/dMMR CRC characterized by poorly differentiated, mucinous, and signet ring cell features. Molecular profiling revealed MLH1/PMS2 loss and MLH1 promoter hypermethylation. Despite his advanced age and multiple comorbidities, the patient underwent surgical resection followed by referral for ICI therapy in lieu of cytotoxic chemotherapy. This case highlights the importance of molecular testing in guiding treatment decisions and supports the consideration of ICIs in select elderly patients. It emphasizes that age alone should not preclude the use of effective, personalized therapies in CRC, particularly in those with good functional status and biomarkers predictive of immunotherapy response.