Abstract
Lynch syndrome (LS) is a hereditary cancer predisposition syndrome associated with multiple malignancies, including colorectal cancer and upper tract urothelial carcinoma (UTUC). We report a 61-year-old woman who initially presented with ascending colon adenocarcinoma and underwent laparoscopic right hemicolectomy. Immunohistochemistry showed loss of MLH1 and PMS2 expression, suggesting deficient mismatch repair. Ten months later, she developed a right renal pelvic mass, which was confirmed by ureteroscopic biopsy as invasive high-grade urothelial carcinoma with squamous differentiation rather than metastatic colon cancer. The urothelial tumor also showed an abnormal MLH1/PMS2 immunophenotype. Subsequent molecular evaluation included plasma cell-free DNA profiling for somatic genomic characterization and peripheral-blood germline analysis for hereditary cancer assessment. Germline testing identified a heterozygous pathogenic variant in NM_000249.4(
MLH1
):c.503dup (p.Asn168fs), establishing the diagnosis of Lynch syndrome. Because the patient strongly wished to preserve renal function, she received single-agent toripalimab at 240 mg every 3 weeks instead of radical nephroureterectomy. Contrast-enhanced CT after three cycles showed tumor reduction, and after six cycles demonstrated further marked regression of the right renal pelvic and upper ureteral lesion, with only residual focal thickening of the renal pelvic wall. At the last follow-up in April 2026, the patient remained clinically stable without evidence of colorectal cancer recurrence or progression of the UTUC. This case highlights the importance of tissue confirmation of newly developed lesions and timely etiologic evaluation of abnormal MMR findings in patients with suspected LS. It adds to emerging evidence that PD-1 blockade may have a kidney-preserving role in carefully selected patients with dMMR LS-associated UTUC, although longer radiographic, endoscopic, cytologic, and histologic surveillance is required.