Clear Cell Renal Cell Carcinoma: Characterizing the Phenotype of Von Hippel–Lindau Mutation Using MRI

Abstract

BackgroundThe von Hippel–Lindau (VHL) mutation is an important alteration in clear cell renal cell carcinoma (ccRCC); however, its imaging phenotype remains unclear.PurposeTo investigate whether MRI features can reflect the VHL mutation status.Study TypeRetrospective.Field Strength/Sequence3 T/fast spin echo T2‐weighted, spin‐echo echo planar diffusion‐weighted, gradient recalled echo T1‐weighted, gradient recalled echo chemical‐shift T1‐weighted, and contrast‐enhanced gradient recalled echo T1‐weighted sequences.PopulationOne hundred five patients with ccRCC who underwent preoperative contrast‐enhanced MRI and subsequent genomic sequencing: 59 consecutive patients from our institution (38 [64.41%] with VHL mutations) formed a training cohort, and 46 from The Cancer Genome Atlas (TCGA) database (24 [52.17%] with VHL mutations) formed an independent test cohort.AssessmentTwo radiologists, with 23 and 33 years of experience respectively, jointly evaluated the semantic MRI features of the primary lesion in ccRCCs to propose potential features related to VHL mutations in both cohorts. Three additional readers, with 5, 7, and 10 years of experience respectively, independently reviewed all lesions to assess the interobserver agreement of MRI features. A VHL mutational likelihood score (VHL‐MULIS) system was constructed using the training cohort and validated using the independent test cohort.Statistical TestsFisher's test or chi‐square test, t‐test or Mann–Whitney U test, logistic regression, Cohen's kappa (κ), area under the receiver operating characteristic curve (AUC). A two‐sided P value <0.05 was considered statistically significant.ResultsIn both the local and public cohorts, T2‐weighted signal intensity and presence of microscopic fat from primary lesions were significantly associated with VHL mutation status. The VHL‐MULIS incorporated maximum diameter, T2‐weighted signal intensity, and presence of microscopic fat in the training cohort and demonstrated promising diagnostic ability (AUC, 0.82; sensitivity, 0.79; specificity, 0.82) and substantial interobserver agreement (κ, 0.787) in the test cohort.Data ConclusionThe VHL mutation exhibited a distinct MRI phenotype. Integrating multiple semantic MRI features has potential to reflect the mutation status in patients with ccRCC.Evidence Level3Technical EfficacyStage 2