Exceptional Response to Pembrolizumab Immunotherapy in a Young Patient With Lynch Syndrome-Associated Metastatic...

Microsatellite instability-high (MSI-H) colorectal cancers demonstrate significant responses to immune checkpoint inhibitors. Lynch syndrome, caused by germline mismatch repair gene mutations, typically presents with MSI-H tumours. We report a remarkable case of complete pathological response to pembrolizumab in a young patient with extensive Lynch syndrome-associated metastatic colorectal cancer. A woman in her early 30s with a strong family history of malignancy presented with progressive fatigue and anaemia. Investigations revealed moderately differentiated adenocarcinoma of the hepatic flexure with extensive metastatic disease, including innumerable liver metastases, retroperitoneal lymphadenopathy, and ascites. Molecular testing demonstrated MSI-H status with loss of MutS Homolog 2 (MSH2) and MutS Homolog 6 (MSH6) expression, v-Raf murine sarcoma viral oncogene homolog B (BRAF) wild-type, consistent with Lynch syndrome. Baseline carcinoembryonic antigen (CEA) was approximately 272 ng/mL. In a healthy adult who smokes, CEA is considered within normal limits at a level less than or equal to 5 ng/ml. Given the MSI-H phenotype, first-line pembrolizumab immunotherapy was commenced rather than conventional chemotherapy. The patient demonstrated a dramatic, sustained response over 24 months of pembrolizumab. CEA declined from approximately 300 ng/mL to 1.0 ng/mL. Serial imaging showed progressive tumour reduction with transformation of solid liver metastases into cystic lesions. Post-treatment Positron Emission Tomography-Computed Tomography (PET-CT) demonstrated a complete metabolic response. Following the completion of immunotherapy, the patient underwent right hemicolectomy. Histopathological examination revealed no viable cancer cells in the entire surgical specimen, confirming complete pathological response (ypT0, ypN0, R0). Immune-related adverse events were manageable and did not require treatment discontinuation. The patient remains under active surveillance with stable residual cystic liver lesions and no evidence of disease progression. This case demonstrates that complete pathological responses to pembrolizumab are achievable in MSI-H metastatic colorectal cancer. Universal MSI/mismatch repair (MMR) testing is essential to identify candidates for first-line immunotherapy, and Lynch syndrome should be considered in young patients with MSI-H tumours and a family history of malignancy.