eMedicine Specialties > Radiology > Multisystem

Von Hippel-Lindau Syndrome: Imaging

Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, LRCP, Chairman of Medical Imaging, Professor of Radiology, NGHA, King Fahad National Guard Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia
Coauthor(s): Ian Turnbull, MD, Lecturer, Department of Radiology, University of Manchester; Consulting Neuroradiologist, Hope Hospital, Salford, Manchester and North Manchester Hospital; Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute; Riyadh Al-Okaili, MBBS, Interventional/Therapeutic and Diagnostic Neuro-Radiologist, King Abdulaziz Medical City
Contributor Information and Disclosures

Updated: Feb 6, 2008

Radiography

Findings

Plain radiographs have little to contribute. Calcification within the orbits in retinal lesions may be difficult to see. The rare, associated bone cysts and osseous hemangiomas may be fairly well defined on plain radiographs.^19,20

Degree of Confidence

Confidence in the diagnosis of VHL with plain radiographs is low.

False Positives/Negatives

Hemangiomas of the bone must be differentiated from osteoblastic metastases, lesions due to Paget disease, lymphoma, and monostotic fibrous dysplasia.

Computed Tomography

Findings

• Hemangioblastomas of the CNS are demonstrated as cystic lesions with a 3- to 15-mm mural nodule in 75% of patients. They are demonstrated as an enhancing lesion with multiple cystic areas in 15% of patients and as an enhancing solid mass in 10%. The cerebellum is most commonly involved, followed by the medulla, the spinal cord, and even the spinal nerve roots. Supratentorial hemangioblastomas are rare, but they have been reported.^11,14,19,20
• Hemangioblastomas usually do not become calcified, and this is a finding that helps in differentiating these lesions from cystic astrocytomas (which are calcified in 25% of patients). Typical pilocytic cystic astrocytomas also occur in patients much younger than most patients with hemangioblastomas.
• Choroidal capillary hemangiomas are aggressive lesions that are histologically similar to cerebellar hemangioblastomas. Approximately 25-30% of these lesions occur in patients with VHL. CT scans demonstrate enhancing lesions.
• Retinal hemangiomas are too small to be depicted on CT scans, and the diagnosis chiefly depends on the results of an ophthalmoscopic examination.
• CT has a low sensitivity in the detection of renal cell carcinoma associated with VHL because of its inability to reliably differentiate cystic renal cell carcinomas, cancers within a cyst, and atypical cysts. Therefore, a multimodality approach is more appropriate.
• Renal adenomas are potentially premalignant. These adenomas are usually smaller than 3 cm, are subcapsular cortical, and are impossible to differentiate from renal cell carcinomas. They are multiple in 25% of patients.
• Endolymphatic sac tumors are destructive and contain calcification centered on the retrolabyrinthine region. All papillary endolymphatic sac tumors have a thin peripheral rim of calcification, representing the expanded cortex of petrous bone.
• Endolymphatic sac tumors are slow growing and spread in 2 directions (ie, laterally toward the external ear, in the direction of the jugular foramen, and medially into the cerebellopontine angle).
• On CT scans, the margins of these tumors are geographic or moth-eaten in appearance, and the intratumoral bone appears reticular or spiculated.
• After the intravenous administration of contrast material, areas of patchy enhancement are interspersed with cystic areas.
• Although the lesion is a benign lesion, it typically has elevated tumor blood volume on perfusion CT, which is more typical for malignant lesions.

Degree of Confidence

CT findings are not reliable in differentiating cystic renal cell carcinomas, cancers within a cyst, and atypical cysts. Differentiating a renal cell adenoma from a renal cell carcinoma is impossible.

False Positives/Negatives

The differential diagnosis of VHL should include sporadic hemangioblastoma, cystic astrocytoma, arachnoid cyst, cystic metastases, renal adenoma, renal cell carcinoma, renal cysts, pancreatic islet cell tumors, and MEN 2. Tumors of the endolymphatic sac may mimic other cerebellopontine tumors.

Magnetic Resonance Imaging

Findings

Hemangioblastomas occur throughout the CNS, but they have several favored locations, including the cerebellum (most common site), medulla, spinal cord, and retina. Although hemangioblastomas can occur as isolated tumors, retinal tumors are mostly confined to VHL.^11,19,20

• MRI appearances of a hemangioblastoma are those of a well-demarcated cystic lesion with a highly vascular mural nodule that abuts on the pia mater.
• Appearances of the cystic component vary depending on the protein concentration and/or presence of hemorrhage within the cyst. The cystic component may be isointense relative to cerebrospinal fluid (CSF) on images obtained with all pulse sequences, but more often, it is slightly hyperintense relative to CSF on T1- and T2-weighted images.
• Mural nodules are slightly hypointense on T1-weighted images and hyperintense on T2-weighted images, and they are avidly enhancing after the administration of contrast material.
• Large feeding or draining vessels are often present at the periphery and within the solid component, and they may show tubular areas of flow void on spin-echo images.
• Although the lesion is benign, it may resemble malignant lesions on advanced MR images. It may have elevated relative tumor blood volume on perfusion MR. Similarly, it may show elevated choline on MR spectroscopy.
• Endolymphatic sac tumors are heterogeneous on both T1- and T2-weighted images. They are associated with focal high signal intensity on T1-weighted images due to subacute hemorrhage and with areas of low signal intensity due to calcification or hemosiderin.
• Blood and protein-filled cysts have high signal intensity on both T1-weighted and T2-weighted images; a finding of these cysts may suggest the diagnosis.
• Tumors larger than 2 cm may have flow voids.
• After the administration of contrast material, the tumor enhances heterogeneously.
• On MRIs, choroidal capillary hemangiomas associated with VHL are minimally hyperintense on T1-weighted images. They may mimic ocular melanoma, but unlike pigmented melanoma, they are usually hyperintense on T2-weighted images.
• As a result of the small size of retinal hemangiomas (1.5-2.0 mm), they are usually not identified on MRIs.
• Spinal hemangioblastomas are intramedullary tumors in most patients (75%), but they may be radicular (20%) or intradural extramedullary (5%). Most of these tumors are located in the cervicothoracic spine. They usually expand the cord and have an intratumoral cystic component. On MRIs, they appear as a well-demarcated gadolinium-enhancing mass. Spinal hemangioblastomas are an unusual cause of cryptic subarachnoid hemorrhage. Patients with subarachnoid hemorrhage with negative cerebral angiography may benefit from contrast-enhanced spinal MRI to rule out an occult spinal hemangioblastoma.
• An intramural nodule that enhances intensely may be visible.
• Large dorsally placed draining veins may appear as curvilinear areas of signal void.
• A syrinx is a frequently associated finding.
• A pheochromocytoma associated with VHL has MRI appearances no different from those of the sporadic form. The tumor appears isointense or slightly hypointense relative to the liver on T1-weighted images, and it is extremely hyperintense on T2-weighted images.

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy . The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans.

As of late December 2006, the FDA had received reports of 90 such cases. Worldwide, over 200 cases have been reported, according to the FDA. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.

Degree of Confidence

MRI is the modality of choice for imaging the central nervous system in patients in whom hemangioblastoma is suggested and for screening asymptomatic patients with VHL and their relatives at risk for VHL.

False Positives/Negatives

False-positive diagnoses may occur with cystic astrocytomas, which are usually smaller than 5 cm in diameter; these may be calcified, and they usually have thicker walls. Cystic metastases occasionally resemble a hemangioblastoma superficially. Spinal hemangioblastomas must be differentiated from intramedullary hemorrhage.

Endolymphatic sac tumors may mimic other cerebellopontine tumors. Nonfunctioning adrenal adenomas, adrenocortical adenomas, and adrenal cysts must be differentiated from pheochromocytomas associated with VHL.

Ultrasonography

Findings

The sensitivity of ultrasonography in the detection of the primary lesion in renal cell carcinoma is comparable to that of CT. Ultrasonography is the modality of choice in screening the abdomen in patients with known VHL. This is a useful examination for imaging the retina; sonograms may show small hypoechoic masses, most often in the temporal retina.²⁰

Degree of Confidence

Ultrasonography is an excellent modality for screening the abdomen in patients with known VHL or their at-risk relatives. It has a high sensitivity in depicting cystic intra-abdominal masses and in characterizing the contents of cysts.

False Positives/Negatives

Differentiating a renal cell adenoma from a renal cell carcinoma may not be possible. Similarly, difficulties may be encountered in differentiating a complex benign cyst from cystic malignant transformation.

Nuclear Imaging

Findings

Radionuclide studies are increasingly valuable in diagnosing CNS neoplasms, in monitoring therapy, and in defining functional characteristics that are not demonstrated well on conventional cross-sectional images.²⁰

Much of the present value of nuclear medicine is in positron emission tomography (PET). PET with fluorodeoxyglucose (FDG) provides an indication of metabolic activity of CNS tumors; this finding is well correlated with the tumor growth rate in most tumors. However, this correlation may not be applicable to some tumors such as pilocytic astrocytomas and hemangioblastomas, which are histologically benign but may resemble high-grade lesions on FDG-PET. FDG-PET scans are unaffected by postoperative reactions or steroids, and they can provide information about residual tumor or tumor recurrence. Many centers prefer to use perfusion MR/CT instead of PET for essentially the same purpose. 

Radionuclides can also be used (1) to detect bone metastases resulting from primary malignant bone lesions due to malignancies associated with VHL and (2) to assess renal function prior to resection of renal tumors. Iodine-131 metaiodobenzylguanidine (¹³¹ I MIBG) is a useful scanning agent in the detection of pheochromocytoma. This technique is particularly useful when clear clinical and laboratory evidence of tumor exists but when CT scans and MRIs demonstrate no abnormality.¹³¹ I MIBG can be used for whole-body scintigraphy in which functioning metastasis from a malignant pheochromocytoma may also be detected; this approach may provide the future therapeutic options (eg,¹³¹ I MIBG methods to treat metastases).

Degree of Confidence

¹³¹ I MIBG uptake has a sensitivity of 80-90% and a specificity of 98% in the detection of pheochromocytoma.

False Positives/Negatives

¹³¹ I MIBG uptake may occur in medullary carcinoma of the thyroid, carcinoid tumors, neuroblastoma, and paragangliomas.

Angiography

Findings

Angiography of hemangioblastoma reveals a hypervascular lesion with intense and prolonged early enhancement of the mural nodule associated with dilated feeding vessels. Endolymphatic sac tumors are hypervascular on angiography, and the blood supply is derived from the external carotid artery. Large tumors have an additional blood supply from the internal carotid artery and posterior circulation.

Degree of Confidence

Angiographic appearances are nonspecific and can occur with other vascular tumors.

False Positives/Negatives

Cystic meningioma and a meningeal hemangiopericytoma may resemble a hemangioblastoma superficially, but confusion is unlikely when the clinical presentation and the other imaging findings are considered.

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