A 26-year-old man comes to the office for follow-up related to painless progressive visual loss in the right eye. Recent ophthalmological evaluation revealed macular edema due to 2 retinal lesions consistent with capillary hemangioblastoma. He underwent laser photocoagulation treatment, and the vision in his right eye has improved. The patient has no other medical conditions. His father died from a cerebral hemorrhage at age 52. MRI of the brain with gadolinium reveals 2 small, cystic, enhancing nodules in the cerebellum. Renal ultrasonography reveals multiple cysts in both kidneys. Which of the following is the most likely diagnosis?

Question

A 26-year-old man comes to the office for follow-up related to painless progressive visual loss in the right eye.  Recent ophthalmological evaluation revealed macular edema due to 2 retinal lesions consistent with capillary hemangioblastoma.  He underwent laser photocoagulation treatment, and the vision in his right eye has improved.  The patient has no other medical conditions.  His father died from a cerebral hemorrhage at age 52.  MRI of the brain with gadolinium reveals 2 small, cystic, enhancing nodules in the cerebellum.  Renal ultrasonography reveals multiple cysts in both kidneys.  Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

11ec25c8_d5d9_2f14_bc81_f981a4a2e507_MD0003_00 This patient has evidence of von Hippel-Lindau (VHL) disease, an autosomal dominant disorder that results in benign and malignant multiorgan tumors. The most common tumors associated with VHL are hemangioblastomas of the central nervous system (CNS) (particularly in the cerebellum, with a classic cystic nodular radiographic appearance) and retina. Although the tumors are noninvasive, symptoms occur due to hemorrhage or compression of surrounding tissues. Bleeding from retinal tumors can lead to retinal exudates and impaired vision or, if untreated, retinal detachment with vision loss. Acute hemorrhage in a brain tumor can result in herniation and death (as likely occurred in this patient's father). Malignant manifestations include renal cell carcinoma (RCC), which occurs in upward of 70% of patients by age 60. RCCs are of the clear cell subtype and typically bilateral. They are often preceded by the formation of multiple renal cysts, which are considered a premalignant condition. Pheochromocytomas also occur with increased frequency and are characterized by paroxysms of hypertension, tachycardia, and diaphoresis. Less common manifestations include vascular tumors of the endolymphatic sac in the ear and pancreatic disease (eg, cysts, neuroendocrine tumors). Genetic testing for germline VHL mutations is key to diagnosis. Management requires frequent tumor surveillance beginning in infancy or early childhood. (Choice A) Autosomal dominant polycystic kidney disease also manifests as CNS and renal disease. However, the CNS disease is largely due to aneurysms (which would not appear as cystic nodules on imaging) rather than tumors; the renal disease is characterized by progressive parenchymal obliteration by cysts, which commonly leads to flank pain and hematuria; and the condition is not associated with retinal capillary hemangioblastomas. (Choice B) Patients with autosomal recessive polycystic kidney disease are typically diagnosed in infancy or childhood. Although the disease is associated with multiple renal cysts, patients characteristically develop end-stage renal disease in early childhood, and hepatobiliary involvement is common (eg, hepatic fibrosis, liver cysts). It is not associated with hemangioblastomas. (Choice C) Li-Fraumeni syndrome is an autosomal dominant disorder associated with alterations of the tumor protein p53 gene. It usually results in early onset of malignancies such as sarcomas, breast cancer, and adrenal carcinomas. CNS disease is characterized by gliomas and medulloblastomas, not hemangiomas. (Choice D) Neurofibromatosis type 2 is another autosomal dominant disorder with marked CNS and ophthalmologic features. However, it is more commonly characterized by schwannomas, particularly of the vestibular nerve, and meningiomas. Cataracts and retinal hamartomas are common ophthalmic manifestations. Educational objective: Von Hippel-Lindau disease is an autosomal dominant disorder resulting in benign and malignant multiorgan tumors. The most common tumors are hemangioblastomas of the central nervous system and retina. Other common manifestations include renal cell carcinoma (often preceded by the formation of premalignant renal cysts) and pheochromocytoma. References: Autosomal dominant polycystic kidney disease: core curriculum 2016. (http://www.ncbi.nlm.nih.gov/pubmed/26530876) Current management of autosomal dominant polycystic kidney disease. (http://www.ncbi.nlm.nih.gov/pubmed/26380198)

A 26-Year-Old Man Comes to the Office for Follow-Up Related