Background Historically, renal cell carcinoma (RCC) is one of the main causes of death in von Hippel-Lindau (VHL) disease. However, the natural history of VHL-related RCC has not been thoroughly elucidated to date. This report described the natural history of VHL-related RCC in a large Chinese VHL cohort and might be helpful in the surveillance and treatment of VHL disease.

Methods In this retrospective study, we included 196 renal tumours from 150 patients with VHL disease. Statistical analysis was used to evaluate the influence of age of onset, sex, family history, unilateral or bilateral tumour, VHL disease type, mutation type, mutation location, and tumour size on tumour growth, metastasis and survival in patients with VHL disease.

Results The mean age of onset was 38.8 years, and the mean initial tumour size was 3.1 cm. The mean linear growth rate was 0.49 cm/year. Patients experienced faster tumour growth when they had later age of onset, larger initial tumour size, missense mutation, mutations locating in exon 3, and when they were not affected by cerebral or retinal haemangioblastomas. Tumours larger than 4 cm grew faster than those smaller than 4 cm. Bilateral tumours, large initial tumours, fast tumour growth and metastasis were risk factors for poor prognosis in VHL-related RCC.

Conclusion This large study demonstrated that age of onset, initial tumour size, concomitant tumours, mutation type and mutation location had an effect on growth rate in VHL-related RCC. Active surveillance may be safe for patients with tumour size less than 4 cm, which is helpful in clinical decision-making.