A Germline BRCA2 Pathogenic Variant Identified by Multigene Panel Testing in Upper Tract Urothelial Carcinoma

Upper tract urothelial carcinoma (UTUC) is associated with Lynch syndrome; however, increasing evidence suggests broader genetic heterogeneity. Although multigene panel testing (MGPT) is increasingly adopted internationally, syndrome-specific genetic testing (SSGT) remains predominant in Japan, potentially limiting detection of non-Lynch hereditary variants. Appropriate selection for expanded germline evaluation remains challenging.

A 41-year-old man with locally advanced UTUC underwent neoadjuvant chemotherapy followed by surgery. His family history included gastrointestinal and breast cancers and did not fit a single hereditary syndrome. Although SSGT was initially considered for Lynch syndrome, germline MGPT was performed after genetic counseling. MGPT identified a germline pathogenic BRCA2 frameshift variant, with no mismatch repair gene variants detected.

This case highlights the value of comprehensive germline evaluation in selected UTUC patients. Urologists should recognize atypical/mixed family histories and consider early genetic referral. Selective MGPT may improve identification of clinically actionable germline variants.