Radiological case of the month: Priya Rastogi, MD, Joseph A. Gagliardi, MD, and Rahul Bharucha, MD.
A 26-year-old man presented with gradual deterioration of vision in his left eye that was progressing toward complete loss of vision. There was no pertinent family history.
[FIGURE 1 OMITTED]
[FIGURE 2 OMITTED]
The postcontrast T1-weighted magnetic resonance (MR) scan revealed solid, enhancing cerebellar lesions (Figure 1), which (along with the ocular lesion) were characteristic findings of von Hippel-Lindau (VHL) disease. The left ocular lesion also showed enhancement and was seen in the posterior aspect of the globe, which suggested the retinal location.
An enhanced computed tomographic (CT) scan of the abdomen demonstrated visceral cysts in the pancreas and the kidneys (Figure 2).
Von Hippel-Lindau disease
Von Hippel-Lindau disease is an autosomal dominant disorder that shows an incomplete penetrance (the gene is inherited, but not always expressed). The disease is linked to a defect in chromosome 3. (1)
Melmon and Rosen2 first proposed the diagnostic criteria of VHL. The diagnosis is based on the presence of multiple hemangioblastomas of the central nervous system (CNS), 1 hemangioblastoma and a visceral manifestation, or 1 central or visceral manifestation in a first-degree relative.3 Other manifestations include papillary cystadenomas of epididymis, endolymphatic sac tumors, renal cysts and tumors, pancreatic cysts, paragangliomas, and visceral angiomatous tumors.
There are at least 3 phenotypes. The first pattern of VHL (type I) is the most common presentation and includes retinal and CNS hemangioblastomas, renal cysts and cancers, and pancreatic cysts without pheochromocytomas. The second most common is type II A, which includes retinal and CNS hemangioblastomas with pheochromocytomas and islet cell tumors of the pancreas. Pancreatic cysts, renal cysts, or malignancies are not present in this type. This has a milder clinical course. Type II B is the most unusual and manifests with retinal and CNS hemangioblastomas and pheochromocytomas, along with renal and pancreatic involvement.
The age of onset of VHL is variable, but the mean age at diagnosis is 25 years. The median age at death is approximately 40 to 50 years. The most common cause of death is either neurological complications of hemangioblastomas or metastasic renal carcinoma. (4)
Manifestations of VHL
Retinal hemangioblastomas: Retinal hemangioblastomas are among the most frequently detected lesions, along with the CNS hemangioblastomas. Up to 45% to 60% of patients with VHL exhibit retinal hemangioblastomas, 50% of which are bilateral. They are usually located peripherally in the retina. Most of these lesions are asymptomatic unless they become very large or involve the optic disk, in which case they can cause vision loss. It has been recommended that indirect ophthalmoscopy or fluorescein angioscopy be used to detect these lesions and monitor their progression. Treatment of these lesions consists of photocoagulation. Enucleation is reserved for patients with severe pain or glaucoma.
Central nervous system hemangioblastomas: Central nervous system hemangioblastomas occur in 3 major sites: the cerebellum, the spine, and the medulla. Hemangioblastomas are usually cystic tumors, but approximately 20% to 25% can be solid. Cerebellar hemangioblastomas with VHL occur in younger patients and are often multiple. Seventy-five percent of hemangioblastomas in VHL occur in the cerebellum, and 25% occur in the spine and the medulla. In the spine, they may be mistaken for a syrinx if the mural nodule is not searched for carefully. On CT imaging, these lesions are usually seen as cystic tumors with an isodense mural nodule that shows striking enhancement postcontrast. On MR imaging, the cystic component of the tumor has a somewhat higher signal than does cerebrospinal fluid. The mural nodule is isointense and shows strong enhancement. Flow voids may be detected in feeding and draining vessels. Cerebral angiography shows a vascular nodule with a dense, prolonged vascular stain. The cyst is commonly seen as a large mass effect on the surrounding vessels. Angiography is performed prior to surgery to reveal the feeding vessels. (5)
Renal manifestations: Renal cysts are present in up to 60% of patients with VHL disease. Renal cell carcinoma is the most frequent non-CNS tumor (in approximately 50% of cases). Renal involvement in VHL is multicentric and bilateral in at least 75% of patients.
Pancreatic lesions: Pancreatic lesions in VHL disease include cysts, cystadenomas, adenocarcinomas, and islet cell tumors. Cysts and cystadenomas of the pancreas are benign in VHL and need not be removed. Strategically located microcystic adenomas in the pancreatic head can cause biliary or pancreatic ductal obstruction.
Pheochromocytomas: Pheochromocytomas are the second most common non-CNS tumor with VHL disease. These are seen in up to 10% to 15% cases. Pheochromocytomas associated with VHL are often multiple, and 50% to 80% are bilateral. Although generally considered benign, pheochromocytomas with VHL can metastasize. Many pheochromocytomas with VHL are asymptomatic and do not have elevated catecholamine levels.
Endolymphatic sac tumors: The endolymphatic sac is located in the inner ear within the vestibular aqueduct. Endolymphatic sac tumors can grow into the cerebellum or the cerebellopontine angle cisterns. They can also involve the inner ear, which can impair balance and hearing. Imaging of the middle ear using high-resolution CT and MR aids in their detection.
Other lesions: Papillary cystadenomas of the epididymis occur in up to 10% to 26% of men with VHL. When they are bilateral, they are virtually pathognomonic of VHL disease. These lesions are usually diagnosed clinically. On ultrasound, they are seen as solid lesions. Multiple cavernous hemangioblastomas and hepatic cysts have also been reported in association with VHL.
Follow-up and screening
Current recommendations for follow-up and screening for VHL consist of periodic (usually yearly) abdominal CT throughout most, if not all, of the patient's life. Other screening regimens that are proposed are clinical, laboratory, and ophthalmoscopic tests. A geneticist should be consulted once a patient is diagnosed with VHL.
Role of the radiologist
The radiologist plays an important role by recognizing this entity, which may be missed by the clinician, who is unaware of the typical constellation of findings. In addition, the radiologist should ensure that the family members are screened, since he or she may be the first to recognize a manifestation of VHL.
The financial and psychological impact of the disease can be devastating. Fortunately, with proper screening and follow-up, the burden can be lessened by detecting tumors while they are still able to be resected.
(1.) Choyke PL, Glenn GM, Walther MM, et al. Von Hippel-Lindau disease: Genetic, clinical, and imaging features. Radiology. 1995;194:629-642.
(2.) Melmon KL, Rosen SW. Lindau's disease. Am J Med. 1964;36: 595-617.
(3.) Fill WL, Lamiell JM, Polk NO. The radiographic manifestations of von Hippel Lindau disease. Radiology. 1979;133:289-295.
(4.) Osborne AG. Diagnostic Neuroradiology: A Text/Atlas. St. Louis, MO: Mosby; 1994.
(5.) Seeger JF, Burke DP,Knake JE, Gabrielsen TO. Computed tomographic and angiographic evaluation of hemangioblastomas. Radiology. 1981;138:65-73.
Priya Rastogi, MD, Joseph A.Gagliardi, MD, and Rahul Bharucha, MD
Prepared by Priya Rastogi, MD, Joseph A. Gagliardi, MD, and Rahul Bharucha, MD, Department of Radiology, St. Vincent's Medical Center, Bridgeport, CT.
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|Author:||Rastogi, Priya; Gagliardi, Joseph A.; Bharucha, Rahul|
|Date:||Nov 1, 2007|
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