To evaluate the proportion of von Hippel-Lindau (VHL) patients with high-grade disease and analyze the association of clinical, pathologic, and genetic factors with high-grade disease.
Clear cell renal cell carcinoma (ccRCC) specimens resected from VHL patients between 2006 and 2021 at the National Cancer Institute were evaluated.
Pathologic, demographic, and genetic data were obtained from clinical records. Multivariate logistic regression models analyzed the association between pathologic grade and demographic information, tumor size, history of previous ipsilateral partial nephrectomy (PN), and germline VHL gene variant.
From 229 patients with VHL, we identified 2,555 ccRCC tumor specimens, of which 203 (7.94%) tumors were high-grade. Over the whole study period, 99 (43.2%) patients developed a high-grade tumor. Older age (OR 1.02, p < 0.0001) and increasing tumor size (OR 1.58, p < 0.0001) were associated with high-grade pathology. Prior ipsilateral PN (OR 2.10, p = 0.002) and germline frameshift VHL variants (OR 2.38, p = 0.01) were also associated with high-grade pathology.
These results demonstrate a strong association between tumor size, age at surgery, re-operative surgery status, and VHL frameshift genetic variant and high-grade pathology in VHL-associated RCC. These factors can be used clinically to assist in surgical intervention decision-making.
Urology. 2025 Jul 23 [Epub ahead of print]
Lauren Loebach, Braden Millan, Maria Antony, Julie Solomon, Christopher Ricketts, Christopher Koller, Milan Patel, Ruben Blachman-Braun, Sandeep Gurram, Cathy Vocke, Maria J Merino, W Marston Linehan, Mark W Ball
Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/40712793