遗传性肾肿瘤综合征：基于问卷的结构化评估方法

Background: Up to 8% of renal tumors have a monogenic cause, yet hereditary renal cell carcinoma (hRCC) syndromes such as von Hippel-Lindau (VHL), Tuberous Sclerosis Complex (TSC), Birt-Hogg-Dubé (BHD), and Hereditary Leiomyomatosis and Renal Cell Cancer remain underdiagnosed. Early diagnosis is critical for patient management, genetic counseling, and family screening. We developed and prospectively validated a structured risk assessment tool (hRCC score) for identifying patients at risk of hereditary renal tumors. Methods: A prospective single-center study was conducted at the University Hospital Cologne (2020-2022) including 200 patients with histologically confirmed renal tumors. The hRCC score incorporated age at diagnosis, multifocal/bilateral disease, histology, extrarenal manifestations, and family history. Patients with a score ≥1.5 were referred for genetic testing using a multiplex MLPA (Multiplex Ligand-dependent Probe Amplification)-based panel including TSC, MET, VHL, FH, SDH-A-D, and FLCN. Results: Of 195 eligible patients, 34.4% (n = 67) had a high-risk hRCC score (≥1.5). Overall, 71 (36.4%) underwent genetic testing; a pathogenic or likely pathogenic variant was detected in 50.7% of tested patients, corresponding to 18.5% of the total cohort. The most common diagnoses were TSC (58.3%), VHL (16.7%), and BHD (11.1%). Confirmed hereditary cases had significantly higher mean hRCC scores (4.67 vs 0.48, P < .0001). Extrarenal manifestations and bilateral or multifocal disease were the strongest predictors. The cutoff of 1.5 yielded 97.2% sensitivity and 79.8% specificity. Conclusions: The hRCC score is an effective clinical screening tool for detecting patients at risk for hereditary renal tumors, demonstrating high diagnostic yield and supporting targeted referral for genetic evaluation.