Case Report: The cystic masquerade in type 1 Von Hippel-Lindau disease: coexisting clear cell renal cell carcinoma and an imaging-suspected pancreatic neuroendocrine tumor

VHL disease is a rare autosomal dominant tumor predisposition syndrome characterized by the development of cystic and solid lesions in multiple organs. Pancreatic and renal cysts are common manifestations and are often considered benign; however, clinically significant neoplasms may arise within or adjacent to these lesions, creating diagnostic challenges. We report a 54-year-old man who presented with progressive obstructive jaundice. Imaging revealed multiple pancreatic cysts, a cystic-solid lesion in the pancreatic head, a hypervascular pancreatic neck nodule suspicious for pNET, a giant left renal mass, bilateral renal cysts, and a Bosniak IV cystic lesion in the right kidney. His medical history was notable for retinal hemangioblastoma resulting in blindness of the right eye more than 30 years earlier. Left radical nephrectomy was performed, and pathology confirmed ccRCC. The pancreatic lesion remained an imaging-suspected pNET rather than a pathologically confirmed neoplasm. Germline testing identified a likely pathogenic VHL variant, confirming the molecular diagnosis of VHL syndrome. Family screening revealed that one of the patient's two sons carried the same variant. The patient subsequently received belzutifan therapy from December 2025 to March 2026. Follow-up contrast-enhanced CT showed no progression of the residual lesions, consistent with short-term radiographic disease stability. This case highlights that extensive cystic disease in VHL syndrome may complicate the recognition and characterization of coexisting solid neoplastic lesions. Particular attention should be paid to enhancing mural nodules, hypervascular solid components, and interval growth when evaluating extensive cystic disease, as these findings may indicate coexisting clinically significant neoplastic lesions requiring further evaluation. Early recognition of VHL syndrome and timely genetic evaluation are essential for preventing delayed diagnosis and organ-threatening complications.