How a 21-Year-Old Patient Achieved Remission Despite Extensive Metastatic Disease

A 21-year-old woman presented with a three-month history of diarrhea, severe fatigue, and significant weight loss. Imaging revealed a large neoplastic mass in the ascending colon, right colic flexure, and liver, with suspected infiltration into the pancreas and duodenum. Urgent surgery confirmed a poorly differentiated adenocarcinoma (T4a N2b) and identified a germline nonsense mutation in the MLH1 gene, establishing Lynch syndrome. Further molecular profiling showed a high tumor mutational burden (TMB) and RAS/BRAF wild-type status.

Despite initial surgical intervention, the patient’s condition rapidly deteriorated. Severe jaundice, obstructive biliary complications, and a large hepatic abscess highlighted the aggressive nature of her disease. A multidisciplinary team considered available options: further surgery, conventional chemotherapy, or enrollment in a targeted clinical trial. Following a brief improvement in liver function, the patient qualified for a phase 2 trial testing combination immunotherapy (nivolumab plus ipilimumab).

Shortly after the first infusion, she experienced acute complications, including hemorrhage from liver metastases and a bloodstream infection. Intensive care, antibiotic therapy, and successful interventional radiology procedures stabilized her condition. Remarkably, within weeks, imaging revealed significant shrinkage of the tumor burden, notably a major reduction of the hepatic abscess. Over the ensuing months, continuous immunotherapy led to progressive clinical and radiological improvement, with no severe adverse events.

After nine treatment cycles, extensive reevaluation showed no evidence of active malignancy. A subsequent liver resection confirmed a complete pathological response, displaying only fibrous tissue, necrosis, and an intense immune infiltrate—no viable tumor cells were detected. Four years post-surgery, the patient remains in excellent health, with regular follow-up exams and Lynch syndrome surveillance ongoing.

This extraordinary outcome illustrates the transformative potential of immunotherapy for advanced mismatch repair-deficient (dMMR) colorectal cancers. Close interdisciplinary collaboration, precise molecular profiling, and early use of combined immune checkpoint inhibitors were pivotal to this success story.