von Hippel-Lindau disease
Assessmentsvon Hippel-Lindau disease
von Hippel-Lindau disease
USMLE® Step 1 style questions USMLE
A 29-year-old man comes to the clinic due to headaches and feeling unstable. Over the past 6 months, the patient gradually has been falling more frequently. He has also been experiencing constant headaches which are worse in the morning. He denies any trauma and does not use alcohol illicit drugs. Medical history is notable for pheochromocytoma, treated with surgery 6 months ago. Vitals are within normal limits. On physical examination, he has difficulty ambulating or standing with feet close together. An MRI is obtained and shown below:
Reproduced from: Wikimedia Commons
Histopathological analysis of this patient's lesion would most likely show which of the following?
von Hippel-Lindau disease exam links
Content Reviewers:Yifan Xiao, MD
Contributors:Tanner Marshall, MS, Evan Debevec-McKenney
Von-Hippel Lindau or VHL is a genetic disease that affects people of all ethnicities and is characterized by tumor development in the CNS, kidneys, adrenal glands and pancreas.
Okay, the VHL gene is a tumor suppressor gene on the short arm of chromosome 3.
It codes for proteins that degrade hypoxia-inducible transcription factor, or HIF. HIF upregulates genes that code for platelet-derived and vascular endothelial growth factors, both of which promote new blood vessel formation and cell growth.
In VHL disease, this tumor suppressor gene is mutated which increases HIF, PDGF, VEGF, and ultimately the risk of tumor formation.
VHL disease is about as common as Huntington Disease, occurring in 1 in 36,000 people.
It is inherited in an autosomal dominant pattern, meaning that a VHL patient has a 50% chance of passing it on to each kid they have.
20% of VHL patients have a de novo or new mutation, meaning they are the first VHL patient in their family.
Alright, the most common tumor type in VHL is hemangioblastoma, a benign blood vessel tumor occurring in about 60% of VHL patients.
In the central nervous system, these can occur in the retina, brain, and spinal cord.
In the eyes, it can cause blindness by detaching the retina.
In the brain and spinal cord, a tumor or the accompanying cyst causes problems when it pushes against surrounding tissue.
For example, if the tumor is in the cerebellum, it can cause ataxia, or the loss of balance.
If it blocks the flow of cerebrospinal fluid, intracranial pressure can rise causing headaches, nausea, and vomiting.
Less common are benign cysts and cyst-like tumors called cystadenomas.
The most concerning, occurring in ~25% of VHL patients, is the endolymphatic sac tumor of the inner ear which can cause deafness.
Cystadenomas can develop in the broad ligament in women, and the epididymis in men, and incidental cysts can occur in the liver, lung, kidney and pancreas in both men and women.
Some tumors associated with VHL can be cancerous.
Von-Hippel Lindau (VHL) is a genetic disease that increases the risk of tumor formation in the CNS, kidneys, adrenal glands, and pancreas. It is caused by a mutated tumor suppressor gene, VHL, which increases the risk of tumor formation by upregulating genes that promote cell growth. VHL is inherited in an autosomal dominant pattern and can lead to various benign and malignant tumors. Hemangioblastoma is the most common tumor type, occurring in about 60% of VHL patients, followed by clear cell renal cell carcinoma, pancreatic neuroendocrine tumors, and pheochromocytomas. Regular surveillance is crucial for improving quality of life and lifespan. Treatment recommendations depend on the tumor type and aim to preserve the function of the affected organ.