DOI: 10.1148/rg.281075052
RadioGraphics 2008;28:65-79
© RSNA, 2008
Imaging Features of von Hippel–Lindau Disease1
Rebecca S. Leung, MBBS, FRCR,
Sona V. Biswas, MBBS, MRCP,
Mark Duncan, MBBCh, FRCR, and
Sheila Rankin, MBBS, FRCR
1 From the Department of Radiology, Guy’s and St Thomas’ Hospitals, St Thomas Street, London SE1 7EH, United Kingdom. Presented as an education exhibit at the 2006 RSNA Annual Meeting. Received March 23, 2007; revision requested April 16 and received May 29; accepted June 22. All authors have no financial relationships to disclose.
Address correspondence to R.S.L. (e-mail: leung.becca{at}gmail.com).
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Abstract
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von Hippel–Lindau (VHL) disease is a rare, autosomal dominantly inherited multisystem disorder characterized by development of a variety of benign and malignant tumors. The spectrum of clinical manifestations of the disease is broad and includes retinal and central nervous system hemangioblastomas, endolymphatic sac tumors, renal cysts and tumors, pancreatic cysts and tumors, pheochromocytomas, and epididymal cystadenomas. The most common causes of death in VHL disease patients are renal cell carcinoma and neurologic complications from cerebellar hemangioblastomas. The various manifestations can be demonstrated with different imaging modalities such as ultrasonography, computed tomography, magnetic resonance imaging, and nuclear medicine. Although genetic testing is available, the manifestations of the syndrome are protean; therefore, imaging plays a key role in identification of abnormalities and subsequent follow-up of lesions. It is also used for screening of asymptomatic gene carriers and their long-term surveillance. Screening is important because the lesions in VHL disease are treatable; thus, early detection allows use of more conservative therapy and may enhance the patient’s length and quality of life. A multidisciplinary team approach is important in screening for VHL disease.
© RSNA, 2008
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LEARNING OBJECTIVES FOR TEST 2
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After reading this article and taking the test, the reader will be able to:
- Recognize the imaging appearances of various manifestations of VHL disease.
- Describe the prevalence, genetics, clinical manifestations, and management of VHL disease.
- Discuss the most appropriate screening investigations for VHL disease and the role of radiologic investigations.
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Introduction
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von Hippel–Lindau (VHL) disease is a rare, inherited, multisystem disorder that is characterized by development of a variety of benign and malignant tumors. Inheritance is autosomal dominant with high penetrance and variable expression, and the condition is associated with inactivation of a tumor suppression gene located on chromosome 3p25.5 (1–3). The prevalence is estimated to be between one in 31,000 and one in 53,000 (3,4).
The spectrum of clinical manifestations of the disease is broad. About 40 different lesions in 14 different organs have been described (5). These include retinal and central nervous system (CNS) hemangioblastomas, endolymphatic sac tumors, renal cysts and tumors, pancreatic cysts and tumors, pheochromocytomas, and epididymal cystadenomas.
The most common lesions are listed in Table 1. At present, the most common causes of death in patients with VHL disease are renal cell carcinomas and neurologic complications from cerebellar hemangioblastomas (4,5). According to the natural history of the disease, the median life expectancy is 49 years (4,5).
The diagnostic criteria for VHL disease (6) include the following: (a) more than one CNS hemangioblastoma, (b) one CNS hemangioblastoma and visceral manifestations of VHL disease, and (c) any manifestation and a known family history of VHL disease.
A variety of manifestations are presented herein by using different imaging modalities such as ultrasonography (US), computed tomography (CT), magnetic resonance (MR) imaging, and nuclear medicine. Although genetic testing is available, because the manifestations of the syndrome are protean, imaging plays a key role in identification of abnormalities and in subsequent follow-up of lesions. It is also important in screening of individuals who carry the VHL gene and are as yet asymptomatic. The role of screening is emphasized because the lesions in VHL disease are treatable. Owing to a combination of intensive radiologic and clinical screening and advanced surgical techniques, the morbidity and mortality of patients with VHL disease has been reduced significantly over the past 20 years (4).
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Genetics
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The inheritance is autosomal dominant; that is, there is a 50% chance of inheriting the VHL gene from a carrier. The gene has high penetrance but variable expression, resulting in a wide variety of manifestations of the disease in affected individuals. New mutations can rarely arise in 1%–3% of cases (7). The VHL gene is a tumor suppressor gene; thus, when both copies of the gene are inactivated by mutation or loss, cell growth is unregulated and tumors in multiple organs result. The location of the tumor suppression gene was isolated to chromosome 3p25.5 (1–3).
In most patients with the clinical manifestations of VHL disease, molecular genetic testing allows identification of a deletion or significant mutation that confirms the diagnosis (8). This permits identification of mutation carriers among asymptomatic family members and may also exclude at-risk relatives by means of negative test results (8). The high-risk gene carriers must undergo regular surveillance both clinically and radiologically. The particular screening protocol used at our institution is outlined in Table 2. Those family members who did not inherit the mutation do not require regular monitoring. Genetic counseling is essential both before and after molecular testing.
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Retinal Hemangioblastomas
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More commonly known as retinal angiomas, retinal hemangioblastomas are among the most frequent and earliest detected VHL disease lesions (5,7,9). They are histologically identical to the hemangioblastomas found in the CNS. The prevalence in patients is reported to be between 45% and 59%, with half of all cases being bilateral (7). Only 5% of cases are diagnosed before the age of 10 years. New lesions may develop quickly, so frequent monitoring is essential.
At nonenhanced T1-weighted MR imaging, lesions demonstrate higher signal intensity than normal vitreous (10). Significant contrast enhancement is seen only in the most severely affected patients. By the time these lesions are picked up at contrast-enhanced MR imaging or CT, they are large and patients already have profound visual loss (7). Thus, screening in this case consists of direct and indirect ophthalmoscopy, with fluorescein angiography in addition (5,7) (Fig 1). Treatment includes laser photocoagulation or cryotherapy.
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Figure 1a. Retinal hemangioblastoma. (a) Ophthalmoscopic image shows a well-defined, orange-red mass associated with a prominent feeding artery and a draining vein. (b) Fluorescein angiogram of this retinal angioma shows its hyper-fluorescence.
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Figure 1b. Retinal hemangioblastoma. (a) Ophthalmoscopic image shows a well-defined, orange-red mass associated with a prominent feeding artery and a draining vein. (b) Fluorescein angiogram of this retinal angioma shows its hyper-fluorescence.
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CNS Hemangioblastomas
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CNS hemangioblastoma is one of the most common manifestations of VHL disease (7). Typical sites are the cerebellum (44%–72%), spinal cord (13%–59%), and medulla (5%) (7,9,11). Supra-tentorial lesions are less common (Fig 2). Only 5%–30% of all cerebellar hemangioblastomas are attributed to VHL disease, whereas 80% of spinal cord hemangioblastomas occur with the disease (7). When associated with VHL disease, they occur at a younger age and have a worse prognosis (7).
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Figure 2a. Hippocampal hemangioblastoma. (a) Axial gadolinium-enhanced T1-weighted MR image shows an enhancing nodule in the right hippocampus. (b) On an axial fluid-attenuated inversion-recovery MR image, the nodule is hyperintense. (c) Coronal gadolinium-enhanced T1-weighted MR image shows the hippocampal nodule.
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Figure 2b. Hippocampal hemangioblastoma. (a) Axial gadolinium-enhanced T1-weighted MR image shows an enhancing nodule in the right hippocampus. (b) On an axial fluid-attenuated inversion-recovery MR image, the nodule is hyperintense. (c) Coronal gadolinium-enhanced T1-weighted MR image shows the hippocampal nodule.
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Figure 2c. Hippocampal hemangioblastoma. (a) Axial gadolinium-enhanced T1-weighted MR image shows an enhancing nodule in the right hippocampus. (b) On an axial fluid-attenuated inversion-recovery MR image, the nodule is hyperintense. (c) Coronal gadolinium-enhanced T1-weighted MR image shows the hippocampal nodule.
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Symptoms of cerebellar lesions include headache, vertigo, ataxia, vomiting, nystagmus, and ninth cranial nerve palsy. Focal spinal pain is the most common symptom of spinal cord hemangioblastoma (11). However, presentation can be late with increased intracranial pressure due to obstructive hydrocephalus and impending spinal cord compression, respectively, and thus diagnosis may be delayed.
Hemangioblastomas are highly vascular lesions that readily enhance with contrast material (Fig 3). They may be solid, cystic, hemorrhagic, or mixed. They are often cystic with a solid enhancing mural nodule (Fig 3d). Spinal cord lesions may be associated with a syrinx (Fig 4c). The MR imaging characteristics are low to medium signal intensity on T1-weighted images and high signal intensity on T2-weighted images. The most useful sequence for detection of these lesions is unenhanced and contrast-enhanced T1-weighted imaging (10). Large feeding or draining vessels within the periphery and solid component may appear as tubular areas of flow void (Fig 4d).
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Figure 3a. Cerebellar hemangioblastomas. (a, b) Axial gadolinium-enhanced T1-weighted (a) and axial T2-weighted (b) MR images show a predominantly cystic tumor with peripheral and septal enhancement and surrounding edema. There is midline shift and compression of the fourth ventricle and quadrigeminal cistern. (c) Axial gadolinium-enhanced T1-weighted MR image shows a solid tumor in the right cerebellum. (d) Coronal gadolinium-enhanced T1-weighted MR image shows a large cystic tumor with an enhancing mural nodule. Surgical changes are seen in the posterior fossa with dilated fourth and lateral ventricles. (e) Coronal gadolinium-enhanced T1-weighted MR image shows a large pseudomeningocele, which was a complication of surgery to remove a large hemangioblastoma. A new tiny hemangioblastoma has recurred in the cerebellum (arrow).
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Figure 3b. Cerebellar hemangioblastomas. (a, b) Axial gadolinium-enhanced T1-weighted (a) and axial T2-weighted (b) MR images show a predominantly cystic tumor with peripheral and septal enhancement and surrounding edema. There is midline shift and compression of the fourth ventricle and quadrigeminal cistern. (c) Axial gadolinium-enhanced T1-weighted MR image shows a solid tumor in the right cerebellum. (d) Coronal gadolinium-enhanced T1-weighted MR image shows a large cystic tumor with an enhancing mural nodule. Surgical changes are seen in the posterior fossa with dilated fourth and lateral ventricles. (e) Coronal gadolinium-enhanced T1-weighted MR image shows a large pseudomeningocele, which was a complication of surgery to remove a large hemangioblastoma. A new tiny hemangioblastoma has recurred in the cerebellum (arrow).
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Figure 3c. Cerebellar hemangioblastomas. (a, b) Axial gadolinium-enhanced T1-weighted (a) and axial T2-weighted (b) MR images show a predominantly cystic tumor with peripheral and septal enhancement and surrounding edema. There is midline shift and compression of the fourth ventricle and quadrigeminal cistern. (c) Axial gadolinium-enhanced T1-weighted MR image shows a solid tumor in the right cerebellum. (d) Coronal gadolinium-enhanced T1-weighted MR image shows a large cystic tumor with an enhancing mural nodule. Surgical changes are seen in the posterior fossa with dilated fourth and lateral ventricles. (e) Coronal gadolinium-enhanced T1-weighted MR image shows a large pseudomeningocele, which was a complication of surgery to remove a large hemangioblastoma. A new tiny hemangioblastoma has recurred in the cerebellum (arrow).
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Figure 3d. Cerebellar hemangioblastomas. (a, b) Axial gadolinium-enhanced T1-weighted (a) and axial T2-weighted (b) MR images show a predominantly cystic tumor with peripheral and septal enhancement and surrounding edema. There is midline shift and compression of the fourth ventricle and quadrigeminal cistern. (c) Axial gadolinium-enhanced T1-weighted MR image shows a solid tumor in the right cerebellum. (d) Coronal gadolinium-enhanced T1-weighted MR image shows a large cystic tumor with an enhancing mural nodule. Surgical changes are seen in the posterior fossa with dilated fourth and lateral ventricles. (e) Coronal gadolinium-enhanced T1-weighted MR image shows a large pseudomeningocele, which was a complication of surgery to remove a large hemangioblastoma. A new tiny hemangioblastoma has recurred in the cerebellum (arrow).
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Figure 3e. Cerebellar hemangioblastomas. (a, b) Axial gadolinium-enhanced T1-weighted (a) and axial T2-weighted (b) MR images show a predominantly cystic tumor with peripheral and septal enhancement and surrounding edema. There is midline shift and compression of the fourth ventricle and quadrigeminal cistern. (c) Axial gadolinium-enhanced T1-weighted MR image shows a solid tumor in the right cerebellum. (d) Coronal gadolinium-enhanced T1-weighted MR image shows a large cystic tumor with an enhancing mural nodule. Surgical changes are seen in the posterior fossa with dilated fourth and lateral ventricles. (e) Coronal gadolinium-enhanced T1-weighted MR image shows a large pseudomeningocele, which was a complication of surgery to remove a large hemangioblastoma. A new tiny hemangioblastoma has recurred in the cerebellum (arrow).
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Figure 4a. Spinal cord hemangioblastomas. (a, b) Sagittal gadolinium-enhanced T1-weighted (a) and sagittal T2-weighted (b) MR images show a cervical hemangioblastoma, which is cystic and expands the spinal cord from C5 to T2. Note the synchronous cerebellar hemangioblastoma. (c) Sagittal gadolinium-enhanced T1-weighted MR image shows tumors associated with a syrinx. (d–f) Sagittal gadolinium-enhanced T1-weighted (d), sagittal T2-weighted (e), and axial gadolinium-enhanced T1-weighted (f) MR images show an intradural but extramedullary hemangioblastoma with large feeding vessels. The tumor compresses the cauda equina.
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Figure 4b. Spinal cord hemangioblastomas. (a, b) Sagittal gadolinium-enhanced T1-weighted (a) and sagittal T2-weighted (b) MR images show a cervical hemangioblastoma, which is cystic and expands the spinal cord from C5 to T2. Note the synchronous cerebellar hemangioblastoma. (c) Sagittal gadolinium-enhanced T1-weighted MR image shows tumors associated with a syrinx. (d–f) Sagittal gadolinium-enhanced T1-weighted (d), sagittal T2-weighted (e), and axial gadolinium-enhanced T1-weighted (f) MR images show an intradural but extramedullary hemangioblastoma with large feeding vessels. The tumor compresses the cauda equina.
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Figure 4c. Spinal cord hemangioblastomas. (a, b) Sagittal gadolinium-enhanced T1-weighted (a) and sagittal T2-weighted (b) MR images show a cervical hemangioblastoma, which is cystic and expands the spinal cord from C5 to T2. Note the synchronous cerebellar hemangioblastoma. (c) Sagittal gadolinium-enhanced T1-weighted MR image shows tumors associated with a syrinx. (d–f) Sagittal gadolinium-enhanced T1-weighted (d), sagittal T2-weighted (e), and axial gadolinium-enhanced T1-weighted (f) MR images show an intradural but extramedullary hemangioblastoma with large feeding vessels. The tumor compresses the cauda equina.
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Figure 4d. Spinal cord hemangioblastomas. (a, b) Sagittal gadolinium-enhanced T1-weighted (a) and sagittal T2-weighted (b) MR images show a cervical hemangioblastoma, which is cystic and expands the spinal cord from C5 to T2. Note the synchronous cerebellar hemangioblastoma. (c) Sagittal gadolinium-enhanced T1-weighted MR image shows tumors associated with a syrinx. (d–f) Sagittal gadolinium-enhanced T1-weighted (d), sagittal T2-weighted (e), and axial gadolinium-enhanced T1-weighted (f) MR images show an intradural but extramedullary hemangioblastoma with large feeding vessels. The tumor compresses the cauda equina.
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Figure 4e. Spinal cord hemangioblastomas. (a, b) Sagittal gadolinium-enhanced T1-weighted (a) and sagittal T2-weighted (b) MR images show a cervical hemangioblastoma, which is cystic and expands the spinal cord from C5 to T2. Note the synchronous cerebellar hemangioblastoma. (c) Sagittal gadolinium-enhanced T1-weighted MR image shows tumors associated with a syrinx. (d–f) Sagittal gadolinium-enhanced T1-weighted (d), sagittal T2-weighted (e), and axial gadolinium-enhanced T1-weighted (f) MR images show an intradural but extramedullary hemangioblastoma with large feeding vessels. The tumor compresses the cauda equina.
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Figure 4f. Spinal cord hemangioblastomas. (a, b) Sagittal gadolinium-enhanced T1-weighted (a) and sagittal T2-weighted (b) MR images show a cervical hemangioblastoma, which is cystic and expands the spinal cord from C5 to T2. Note the synchronous cerebellar hemangioblastoma. (c) Sagittal gadolinium-enhanced T1-weighted MR image shows tumors associated with a syrinx. (d–f) Sagittal gadolinium-enhanced T1-weighted (d), sagittal T2-weighted (e), and axial gadolinium-enhanced T1-weighted (f) MR images show an intradural but extramedullary hemangioblastoma with large feeding vessels. The tumor compresses the cauda equina.
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Treatment of CNS hemangioblastomas involves surgical resection of symptomatic tumors, with preoperative arterial embolization for extensive spinal cord tumors (7,9). However, those hemangioblastomas associated with VHL disease can be difficult to manage surgically, which has led to an interest in use of stereotactic radiosurgical ablation (gamma knife therapy). This has been shown to be particularly useful in VHL disease patients, who tend to present with multiple hemangioblastomas that would otherwise require multiple surgical procedures (12). It also allows highly focused treatment of small to moderate-sized solid tumors (13) and deeply located, inoperable tumors (12). However, its efficacy in VHL disease patients is limited by the tendency for disease to recur and for new tumors to develop (13).
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Endolymphatic Sac Tumors
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Most endolymphatic sac tumors occur sporadically, but an association with VHL disease has been reported rarely (14). It has been found that VHL disease increases the risk of developing such tumors, with a tendency for bilateral lesions. The prevalence of bilateral tumors is reported to be 7% (15), increasing in those patients with hearing loss.
Endolymphatic sac tumors are slow-growing tumors that consist of areas of hemorrhage, hemosiderin, and cholesterol clefts with inflammatory giant cell reaction. They are located in the posterior part of the petrous temporal bone and cause local bone destruction as well as new bone formation. Although locally invasive, they are not known to metastasize (15).
The clinical presentation is late, with unilateral hearing loss and vestibular dysfunction. Facial nerve palsy is seen once the tumor becomes large (>3 cm) (11). At high-resolution CT, the bone destruction is geographic or moth-eaten and the intratumoral bone is stippled, reticular, or spiculated (14) (Fig 5a). There is a peripheral rim of calcification. At MR imaging, the signal intensity is heterogeneous with either a peripheral rim of high signal intensity or hyperintense foci, and contrast enhancement is heterogeneous (7,14) (Fig 5b). Angiograms reveal a hypervascular tumor. Early detection is important because prompt surgical intervention may prevent further hearing loss (7).
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Figure 5a. Endolymphatic sac tumor. Axial CT scan (a) and unenhanced T1-weighted MR image (b) show a tumor with its epicenter on the posterior petrous ridge in the region of the vestibular aqueduct. The CT scan shows geographic bone destruction and intratumoral osseous spicules, and the MR image shows hyperintense foci, features characteristic of endolymphatic sac tumor.
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Figure 5b. Endolymphatic sac tumor. Axial CT scan (a) and unenhanced T1-weighted MR image (b) show a tumor with its epicenter on the posterior petrous ridge in the region of the vestibular aqueduct. The CT scan shows geographic bone destruction and intratumoral osseous spicules, and the MR image shows hyperintense foci, features characteristic of endolymphatic sac tumor.
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Renal Cysts and Tumors
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Renal cysts occur in 59%–63% of patients, and renal cell carcinoma (RCC) in 24%–45% (7). Lesions are bilateral in as many as 75% of patients (7,16). CNS involvement usually precedes the onset of renal disease (17), but renal tumors do occur at a younger age (mean, 30–36 years) in VHL disease than in the general population (3,7). Periodic screening is important because if left untreated, RCC carries a poor prognosis and metastasizes widely (18).
The renal lesions vary from simple cysts to hyperplastic cysts and cysts containing clear cell carcinoma; solid tumors have also been described (16). The full pathologic spectrum may occur in a single kidney. It is thought that two types of cysts exist in VHL disease: those with malignant potential and those without—that is, tumors can arise from cystic precursors or completely de novo (7). Thus, serial imaging is important in detecting any malignant transformation of seemingly benign cysts. Studies have shown that cysts commonly grow over time. However, some involute leaving small scars, and in others the solid component may enlarge (16). There is no correlation between cyst size and number and malignant potential (7).
US is useful in distinguishing a solid from a cystic lesion (Fig 6). RCCs associated with VHL disease are either multicentric and bilateral solid hypervascular masses or complex cystic masses with mural nodules and thick septa. CT is more sensitive than US for detection of small (<2 cm) lesions (7); cysts demonstrate little or no wall enhancement, and solid components enhance briskly (50–200 HU) after contrast material administration (19) (Fig 7b, 7c). Nevertheless, US may be preferable for surveillance purposes to reduce the amount of radiation exposure to the patient to as low as reasonably possible. CT should be performed in cases of suspicious or equivocal US findings, for example, to further evaluate a solid mass or complex cyst. CT is also useful in cases of multiple renal cysts, where the renal architecture has been distorted and is difficult to analyze with US (18).
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Figure 6a. Renal cysts. US images of the same kidney show a mixture of simple and complex cysts. (a) A simple renal cyst has a thin, imperceptible wall and anechoic fluid contents. (b) A complex renal cyst has thick walls, septa, and mural nodules.
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Figure 6b. Renal cysts. US images of the same kidney show a mixture of simple and complex cysts. (a) A simple renal cyst has a thin, imperceptible wall and anechoic fluid contents. (b) A complex renal cyst has thick walls, septa, and mural nodules.
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Figure 7a. RCCs. (a) US image shows multiple lesions of mixed echotexture, which represent multiple RCCs. (b, c) Axial contrast-enhanced CT scans (b obtained at a higher level than c) show a mixture of simple cysts and solid enhancing lesions in the kidney, findings consistent with RCCs. Note the right nephrectomy, which was performed because of RCCs, and the common bile duct stent, which was inserted to relieve obstruction caused by extrinsic mass effect from pancreatic cysts. (d, e) Axial T2-weighted (d) and coronal T1-weighted (e) MR images show the right nephrectomy, the multiple solid RCCs of heterogeneous signal intensity (arrows), and the multiple simple cysts. Note the pseudocapsule surrounding the tumors on the T2-weighted image. (f) Photomicrograph (original magnification, x20; hematoxylin-eosin stain) shows the histologic features of a clear cell type RCC from a patient with VHL disease. The tumor cells have clear cytoplasm and hyperchromatic nuclei with interspersed small capillaries. (Fig 7f courtesy of Ashish Chandra, MBBS, MRCPath, St Thomas’ Hospital, London, United Kingdom.)
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Figure 7b. RCCs. (a) US image shows multiple lesions of mixed echotexture, which represent multiple RCCs. (b, c) Axial contrast-enhanced CT scans (b obtained at a higher level than c) show a mixture of simple cysts and solid enhancing lesions in the kidney, findings consistent with RCCs. Note the right nephrectomy, which was performed because of RCCs, and the common bile duct stent, which was inserted to relieve obstruction caused by extrinsic mass effect from pancreatic cysts. (d, e) Axial T2-weighted (d) and coronal T1-weighted (e) MR images show the right nephrectomy, the multiple solid RCCs of heterogeneous signal intensity (arrows), and the multiple simple cysts. Note the pseudocapsule surrounding the tumors on the T2-weighted image. (f) Photomicrograph (original magnification, x20; hematoxylin-eosin stain) shows the histologic features of a clear cell type RCC from a patient with VHL disease. The tumor cells have clear cytoplasm and hyperchromatic nuclei with interspersed small capillaries. (Fig 7f courtesy of Ashish Chandra, MBBS, MRCPath, St Thomas’ Hospital, London, United Kingdom.)
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Figure 7c. RCCs. (a) US image shows multiple lesions of mixed echotexture, which represent multiple RCCs. (b, c) Axial contrast-enhanced CT scans (b obtained at a higher level than c) show a mixture of simple cysts and solid enhancing lesions in the kidney, findings consistent with RCCs. Note the right nephrectomy, which was performed because of RCCs, and the common bile duct stent, which was inserted to relieve obstruction caused by extrinsic mass effect from pancreatic cysts. (d, e) Axial T2-weighted (d) and coronal T1-weighted (e) MR images show the right nephrectomy, the multiple solid RCCs of heterogeneous signal intensity (arrows), and the multiple simple cysts. Note the pseudocapsule surrounding the tumors on the T2-weighted image. (f) Photomicrograph (original magnification, x20; hematoxylin-eosin stain) shows the histologic features of a clear cell type RCC from a patient with VHL disease. The tumor cells have clear cytoplasm and hyperchromatic nuclei with interspersed small capillaries. (Fig 7f courtesy of Ashish Chandra, MBBS, MRCPath, St Thomas’ Hospital, London, United Kingdom.)
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Figure 7d. RCCs. (a) US image shows multiple lesions of mixed echotexture, which represent multiple RCCs. (b, c) Axial contrast-enhanced CT scans (b obtained at a higher level than c) show a mixture of simple cysts and solid enhancing lesions in the kidney, findings consistent with RCCs. Note the right nephrectomy, which was performed because of RCCs, and the common bile duct stent, which was inserted to relieve obstruction caused by extrinsic mass effect from pancreatic cysts. (d, e) Axial T2-weighted (d) and coronal T1-weighted (e) MR images show the right nephrectomy, the multiple solid RCCs of heterogeneous signal intensity (arrows), and the multiple simple cysts. Note the pseudocapsule surrounding the tumors on the T2-weighted image. (f) Photomicrograph (original magnification, x20; hematoxylin-eosin stain) shows the histologic features of a clear cell type RCC from a patient with VHL disease. The tumor cells have clear cytoplasm and hyperchromatic nuclei with interspersed small capillaries. (Fig 7f courtesy of Ashish Chandra, MBBS, MRCPath, St Thomas’ Hospital, London, United Kingdom.)
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Figure 7e. RCCs. (a) US image shows multiple lesions of mixed echotexture, which represent multiple RCCs. (b, c) Axial contrast-enhanced CT scans (b obtained at a higher level than c) show a mixture of simple cysts and solid enhancing lesions in the kidney, findings consistent with RCCs. Note the right nephrectomy, which was performed because of RCCs, and the common bile duct stent, which was inserted to relieve obstruction caused by extrinsic mass effect from pancreatic cysts. (d, e) Axial T2-weighted (d) and coronal T1-weighted (e) MR images show the right nephrectomy, the multiple solid RCCs of heterogeneous signal intensity (arrows), and the multiple simple cysts. Note the pseudocapsule surrounding the tumors on the T2-weighted image. (f) Photomicrograph (original magnification, x20; hematoxylin-eosin stain) shows the histologic features of a clear cell type RCC from a patient with VHL disease. The tumor cells have clear cytoplasm and hyperchromatic nuclei with interspersed small capillaries. (Fig 7f courtesy of Ashish Chandra, MBBS, MRCPath, St Thomas’ Hospital, London, United Kingdom.)
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Figure 7f. RCCs. (a) US image shows multiple lesions of mixed echotexture, which represent multiple RCCs. (b, c) Axial contrast-enhanced CT scans (b obtained at a higher level than c) show a mixture of simple cysts and solid enhancing lesions in the kidney, findings consistent with RCCs. Note the right nephrectomy, which was performed because of RCCs, and the common bile duct stent, which was inserted to relieve obstruction caused by extrinsic mass effect from pancreatic cysts. (d, e) Axial T2-weighted (d) and coronal T1-weighted (e) MR images show the right nephrectomy, the multiple solid RCCs of heterogeneous signal intensity (arrows), and the multiple simple cysts. Note the pseudocapsule surrounding the tumors on the T2-weighted image. (f) Photomicrograph (original magnification, x20; hematoxylin-eosin stain) shows the histologic features of a clear cell type RCC from a patient with VHL disease. The tumor cells have clear cytoplasm and hyperchromatic nuclei with interspersed small capillaries. (Fig 7f courtesy of Ashish Chandra, MBBS, MRCPath, St Thomas’ Hospital, London, United Kingdom.)
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MR imaging is especially useful in young patients and those with renal failure who still require screening. The best sequences are fast T2-weighted imaging or contrast-enhanced T1-weighted imaging with fat suppression (3,4,7). Simple cysts are hypointense on T1-weighted images and hyperintense on T2-weighted images, with no enhancement after administration of gadolinium contrast material. Complex or solid lesions enhance on postcontrast T1-weighted images and may also demonstrate a low-signal-intensity pseudocapsule on T2-weighted images (4) (Fig 7d).
Given the high risk of recurrence and risks associated with renal replacement (dialysis or transplantation), the preferred method of treatment for VHL disease–associated RCC is nephron-sparing surgery (eg, partial nephrectomy, enucleation) (19). At our institution, we also perform radiofrequency ablation in patients who are poor surgical candidates, cases of small tumors (<3 cm), and cases of single tumors between 3 and 5 cm that would be difficult to remove with partial nephrectomy. Tumors greater than 5 cm are treated with ablation only for palliation, for example, in massive hematuria. In addition to size, location also influences the outcome of the procedure, with peripheral exophytic masses exhibiting a higher success rate than central masses (20).
Successful ablation is interpreted as an area of complete coagulation necrosis with little or no enhancement at CT or MR imaging (21) (Fig 8). Follow-up is usually with CT at 1 day after the procedure, at 3 months, and then at 6-month intervals (21). Ablation is particularly suitable for patients with VHL disease because they have multiple RCCs. Early detection of RCCs with screening enables such treatment to be performed rather than radical nephrectomy, and early treatment may prevent metastasis (18,19).
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Figure 8a. Results of radiofrequency ablation of a right lower pole RCC. (a, b) Axial contrast-enhanced CT scan (a) and T1-weighted MR image (b) show a left nephrectomy and a nonenhancing scar on the right kidney (arrow), a finding indicative of successful coagulation necrosis from radiofrequency ablation. An induction coil and track through the skin from radiofrequency ablation are visible. (c) Renal MR angiogram shows thrombosis of the lower pole vessels.
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Figure 8b. Results of radiofrequency ablation of a right lower pole RCC. (a, b) Axial contrast-enhanced CT scan (a) and T1-weighted MR image (b) show a left nephrectomy and a nonenhancing scar on the right kidney (arrow), a finding indicative of successful coagulation necrosis from radiofrequency ablation. An induction coil and track through the skin from radiofrequency ablation are visible. (c) Renal MR angiogram shows thrombosis of the lower pole vessels.
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Figure 8c. Results of radiofrequency ablation of a right lower pole RCC. (a, b) Axial contrast-enhanced CT scan (a) and T1-weighted MR image (b) show a left nephrectomy and a nonenhancing scar on the right kidney (arrow), a finding indicative of successful coagulation necrosis from radiofrequency ablation. An induction coil and track through the skin from radiofrequency ablation are visible. (c) Renal MR angiogram shows thrombosis of the lower pole vessels.
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Pancreatic Cysts and Tumors
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Pancreatic involvement in VHL disease includes simple pancreatic cysts (50%–91%) (3) (Fig 9), serous microcystic adenomas (12%) (3), and rarely adenocarcinomas (7) (Fig 10). Pancreatic neuroendocrine tumors (5%–17%) also occur (4,5). Combined lesions occur, but neuroendocrine tumors and cystic lesions only rarely exist together (3). Mucinous macrocystic adenomas, which are regarded as premalignant, have so far not been described in VHL disease (22), to our knowledge. The reported prevalence of pancreatic involvement in VHL disease varies from 0% in some family groups to 77% in others (3,4).
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Figure 10a. Pancreatic adenocarcinoma. (a) Axial T2-weighted MR image shows a large mass in the head of the pancreas. (b) Photomicrograph (original magnification, x20; hematoxylin-eosin stain) shows the histologic features of a pancreatic papillary adenocarcinoma that arose in a large duct. The tumor consists of fibrovascular cores lined by malignant cells with abundant clear cytoplasm and pleomorphic nuclei. (Fig 10b courtesy of Ashish Chandra, MBBS, MRCPath, St Thomas’ Hospital, London, United Kingdom.)
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Figure 10b. Pancreatic adenocarcinoma. (a) Axial T2-weighted MR image shows a large mass in the head of the pancreas. (b) Photomicrograph (original magnification, x20; hematoxylin-eosin stain) shows the histologic features of a pancreatic papillary adenocarcinoma that arose in a large duct. The tumor consists of fibrovascular cores lined by malignant cells with abundant clear cytoplasm and pleomorphic nuclei. (Fig 10b courtesy of Ashish Chandra, MBBS, MRCPath, St Thomas’ Hospital, London, United Kingdom.)
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Pancreatic cysts are extremely rare in the general population (23); therefore, the presence of a single cyst in an individual undergoing VHL disease screening because of a family history makes it highly likely that the person has VHL disease. In general, cystic pancreatic lesions in VHL disease are asymptomatic or associated with only mild symptoms (22). As a result, they are typically detected during screening examinations and may therefore facilitate the identification of gene carriers. In addition, pancreatic lesions may be the only abdominal manifestation and may precede any other manifestation by several years (23); thus, recognition permits earlier diagnosis of VHL disease.
When symptoms are present, they usually consist of minor abdominal discomfort. Rarely, severe pancreatic cystic disease results in exocrine insufficiency requiring enzyme replacement (23). Episodes of pancreatitis and biliary obstruction are also rare, with only two cases reported in association with cystadenomas of the pancreas (22), to our knowledge. Various studies have shown no significant progression of cystic pancreatic lesions (22) and therefore conservative management is recommended in these cases. On the other hand, pancreatic adenocarcinomas carry a poor prognosis and only 10%–15% are potentially resectable.
Lesions are commonly detected with US and CT. These modalities are similar in terms of sensitivity and specificity (22). Therefore, US is adequate for screening purposes, with CT used for suspicious lesions. Thin-section CT through the pancreas improves the detection of small lesions. The walls of simple cysts enhance poorly or not at all (Fig 9). Microcystic adenomas (serous cystadenomas) are usually well circumscribed, with numerous small cysts measuring up to 2 cm, which are radially aligned with a central calcified stellate scar (23). Enhancement occurs at the periphery of these microcysts (3). Some cysts are so small as to be radiologically indistinguishable; at US they may appear solid due to numerous acoustic interfaces (7). It may be impossible to distinguish a cluster of benign cysts from a microcystic adenoma, but because of the benignity of the latter, this has no clinical implications (23).
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Neuroendocrine Pancreatic Tumors
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Neuroendocrine tumors, otherwise known as islet cell tumors, may occur in 5%–17% of patients (4,5) and tend to be unrelated to pancreatic cystic disease. They occur more frequently in patients with pheochromocytomas (4,7,24) and, like the latter, are derived from the neural crest. Most tumors are slow growing, asymptomatic, and nonfunctional (4,24). The functional ones commonly secrete peptides such as insulin, glucagon, gastrin, and somatostatin; thus, clinical presentation is early, when the tumors are small. In VHL disease patients, the nonfunctional neuroendocrine tumors are usually picked up at screening and are usually larger. The frequency of malignancy and metastases in these tumors is low in association with VHL disease (<10%) (4,24), whereas sporadic neuroendocrine tumors metastasize in 60%–92% of cases (24). Owing to the slow rate of growth and the low probability of metastases, lesions may be observed rather than undergoing immediate removal (24).
At US, benign islet cell tumors are well defined, round or oval, and hypoechoic relative to pancreatic parenchyma. At unenhanced CT, they are homogeneous and hypo- or isoattenuating relative to the remainder of the pancreas. They are hypointense on T1-weighted MR images and hyperintense on T2-weighted images, but not as bright as cysts (3,24). Most lesions larger than 2 cm may be visualized with any technique, but those smaller than 2 cm are best seen with contrast-enhanced CT, where intense enhancement in the arterial phase is demonstrated (23) (Fig 11). As the tumor enlarges, areas of calcification, necrosis, and cystic degeneration may be seen (24). Fat-suppressed MR imaging and dynamic gadolinium-enhanced MR imaging are superior to CT in depicting these lesions (4), but US and CT are adequate for screening purposes.
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Figure 11. Pancreatic insulinoma. Axial contrast-enhanced CT scan obtained during the arterial phase shows a homogeneous enhancing lesion (black arrow) in the uncinate process of the pancreas, just posterior to the superior mesenteric vein (white arrow).
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Treatment of neuroendocrine tumors consists of pancreas-sparing procedures, such as distal pancreatectomy if the lesion is located in the pancreatic tail or enucleation if it is in the pancreatic head. However, larger masses may require more aggressive surgery, such as the Whipple procedure (24).
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Pheochromocytomas
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There is a wide reported range of prevalence of pheochromocytoma, ranging from 0% in some family groups to 60% in others (3–5,25). In families with a high prevalence of pheochromocytoma, there is a lower frequency of cerebellar hemangioblastoma and RCC (7). VHL disease–associated pheochromocytomas, as opposed to the sporadic lesions, manifest at a younger age, are multiple and ectopic, and have a very low proportion of malignant tumors (4); 50%–80% are bilateral (3,7). Ectopic sites occur in 15%–18% of cases (3) and include the organ of Zuckerkandl at the origin of the inferior mesenteric artery, glomus jugulare, carotid body, and periaortic, perisplenic, and intrarenal lesions.
Pheochromocytomas arise from the neural crest and produce elevated levels of catecholamines in the serum and urine. However, many lesions are asymptomatic and results of biochemical tests are normal (7). When symptoms are present, they can consist of hypertension, headaches, palpitations, and sweating. Pheochromocytoma is also potentially life threatening; for example, hypertensive crises, myocardial infarction, cardiac failure, stroke, and metastatic disease can occur (7).
Imaging includes CT, MR imaging, and iodine 131 (131I) metaiodobenzylguanidine (MIBG) scintigraphy. The typical appearance at CT is a solid or complex cystic mass that may have areas of necrosis, hemorrhage, and calcifications (3). Marked enhancement is also typically seen, although small areas of the tumor may remain of low attenuation (7) (Fig 12a, 12b). If an adrenal lesion is discovered at CT, MR imaging is then performed, as it is superior to CT in evaluating ectopic sites of pheochromocytoma (7). At MR imaging, 95%–100% of lesions have low or intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images (3,4,7) (Fig 12c, 12d) and show marked gadolinium enhancement. 131I MIBG scanning is 75%–95% sensitive and 98%–100% specific for these tumors (4), but very small lesions may be missed (Fig 12g). This modality is useful when there is clinically diagnosed pheochromocytoma but no lesions have been demonstrated with CT or MR imaging. It is also used to detect metastases from malignant pheochromocytoma.
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Figure 12a. Pheochromocytomas. (a, b) Oblique sagittal (a) and axial (b) contrast-enhanced CT scans show two heterogeneously enhancing solid adrenal lesions. There is stranding of the surrounding fat and a simple left renal cyst. The synchronous enhancing mass in the spinal canal with serpentine feeding vessels is a metastasis from a cerebellar hemangioblastoma. (c, d) Axial T1-weighted (c) and T2-weighted (d) MR images of the same patient as in Figure 10 show a right pheochromocytoma. The lesion is hypointense on the T1-weighted image and hyperintense on the T2-weighted image. Note the synchronous pancreatic adenocarcinoma and simple right renal cyst. (e, f) Axial (e) and coronal (f) images from positron emission tomography/CT of the same patient as in c and d show intense uptake in the right adrenal gland and pancreatic head, findings indicative of the pheochromocytoma and the pancreatic adenocarcinoma, respectively. (g) 131I MIBG scan of the same patient as in a and b shows hepatic uptake, intense uptake in both adrenal glands (arrows), and slight bowel uptake adjacent to the left adrenal gland.
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Figure 12b. Pheochromocytomas. (a, b) Oblique sagittal (a) and axial (b) contrast-enhanced CT scans show two heterogeneously enhancing solid adrenal lesions. There is stranding of the surrounding fat and a simple left renal cyst. The synchronous enhancing mass in the spinal canal with serpentine feeding vessels is a metastasis from a cerebellar hemangioblastoma. (c, d) Axial T1-weighted (c) and T2-weighted (d) MR images of the same patient as in Figure 10 show a right pheochromocytoma. The lesion is hypointense on the T1-weighted image and hyperintense on the T2-weighted image. Note the synchronous pancreatic adenocarcinoma and simple right renal cyst. (e, f) Axial (e) and coronal (f) images from positron emission tomography/CT of the same patient as in c and d show intense uptake in the right adrenal gland and pancreatic head, findings indicative of the pheochromocytoma and the pancreatic adenocarcinoma, respectively. (g) 131I MIBG scan of the same patient as in a and b shows hepatic uptake, intense uptake in both adrenal glands (arrows), and slight bowel uptake adjacent to the left adrenal gland.
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Figure 12c. Pheochromocytomas. (a, b) Oblique sagittal (a) and axial (b) contrast-enhanced CT scans show two heterogeneously enhancing solid adrenal lesions. There is stranding of the surrounding fat and a simple left renal cyst. The synchronous enhancing mass in the spinal canal with serpentine feeding vessels is a metastasis from a cerebellar hemangioblastoma. (c, d) Axial T1-weighted (c) and T2-weighted (d) MR images of the same patient as in Figure 10 show a right pheochromocytoma. The lesion is hypointense on the T1-weighted image and hyperintense on the T2-weighted image. Note the synchronous pancreatic adenocarcinoma and simple right renal cyst. (e, f) Axial (e) and coronal (f) images from positron emission tomography/CT of the same patient as in c and d show intense uptake in the right adrenal gland and pancreatic head, findings indicative of the pheochromocytoma and the pancreatic adenocarcinoma, respectively. (g) 131I MIBG scan of the same patient as in a and b shows hepatic uptake, intense uptake in both adrenal glands (arrows), and slight bowel uptake adjacent to the left adrenal gland.
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Figure 12d. Pheochromocytomas. (a, b) Oblique sagittal (a) and axial (b) contrast-enhanced CT scans show two heterogeneously enhancing solid adrenal lesions. There is stranding of the surrounding fat and a simple left renal cyst. The synchronous enhancing mass in the spinal canal with serpentine feeding vessels is a metastasis from a cerebellar hemangioblastoma. (c, d) Axial T1-weighted (c) and T2-weighted (d) MR images of the same patient as in Figure 10 show a right pheochromocytoma. The lesion is hypointense on the T1-weighted image and hyperintense on the T2-weighted image. Note the synchronous pancreatic adenocarcinoma and simple right renal cyst. (e, f) Axial (e) and coronal (f) images from positron emission tomography/CT of the same patient as in c and d show intense uptake in the right adrenal gland and pancreatic head, findings indicative of the pheochromocytoma and the pancreatic adenocarcinoma, respectively. (g) 131I MIBG scan of the same patient as in a and b shows hepatic uptake, intense uptake in both adrenal glands (arrows), and slight bowel uptake adjacent to the left adrenal gland.
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Figure 12e. Pheochromocytomas. (a, b) Oblique sagittal (a) and axial (b) contrast-enhanced CT scans show two heterogeneously enhancing solid adrenal lesions. There is stranding of the surrounding fat and a simple left renal cyst. The synchronous enhancing mass in the spinal canal with serpentine feeding vessels is a metastasis from a cerebellar hemangioblastoma. (c, d) Axial T1-weighted (c) and T2-weighted (d) MR images of the same patient as in Figure 10 show a right pheochromocytoma. The lesion is hypointense on the T1-weighted image and hyperintense on the T2-weighted image. Note the synchronous pancreatic adenocarcinoma and simple right renal cyst. (e, f) Axial (e) and coronal (f) images from positron emission tomography/CT of the same patient as in c and d show intense uptake in the right adrenal gland and pancreatic head, findings indicative of the pheochromocytoma and the pancreatic adenocarcinoma, respectively. (g) 131I MIBG scan of the same patient as in a and b shows hepatic uptake, intense uptake in both adrenal glands (arrows), and slight bowel uptake adjacent to the left adrenal gland.
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Figure 12f. Pheochromocytomas. (a, b) Oblique sagittal (a) and axial (b) contrast-enhanced CT scans show two heterogeneously enhancing solid adrenal lesions. There is stranding of the surrounding fat and a simple left renal cyst. The synchronous enhancing mass in the spinal canal with serpentine feeding vessels is a metastasis from a cerebellar hemangioblastoma. (c, d) Axial T1-weighted (c) and T2-weighted (d) MR images of the same patient as in Figure 10 show a right pheochromocytoma. The lesion is hypointense on the T1-weighted image and hyperintense on the T2-weighted image. Note the synchronous pancreatic adenocarcinoma and simple right renal cyst. (e, f) Axial (e) and coronal (f) images from positron emission tomography/CT of the same patient as in c and d show intense uptake in the right adrenal gland and pancreatic head, findings indicative of the pheochromocytoma and the pancreatic adenocarcinoma, respectively. (g) 131I MIBG scan of the same patient as in a and b shows hepatic uptake, intense uptake in both adrenal glands (arrows), and slight bowel uptake adjacent to the left adrenal gland.
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Figure 12g. Pheochromocytomas. (a, b) Oblique sagittal (a) and axial (b) contrast-enhanced CT scans show two heterogeneously enhancing solid adrenal lesions. There is stranding of the surrounding fat and a simple left renal cyst. The synchronous enhancing mass in the spinal canal with serpentine feeding vessels is a metastasis from a cerebellar hemangioblastoma. (c, d) Axial T1-weighted (c) and T2-weighted (d) MR images of the same patient as in Figure 10 show a right pheochromocytoma. The lesion is hypointense on the T1-weighted image and hyperintense on the T2-weighted image. Note the synchronous pancreatic adenocarcinoma and simple right renal cyst. (e, f) Axial (e) and coronal (f) images from positron emission tomography/CT of the same patient as in c and d show intense uptake in the right adrenal gland and pancreatic head, findings indicative of the pheochromocytoma and the pancreatic adenocarcinoma, respectively. (g) 131I MIBG scan of the same patient as in a and b shows hepatic uptake, intense uptake in both adrenal glands (arrows), and slight bowel uptake adjacent to the left adrenal gland.
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The treatment of choice is still open adrenalectomy. However, it is now becoming popular to remove pheochromocytomas with laparoscopic partial adrenalectomy or enucleation, although the risk of recurrence is high (3).
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Papillary Cystadenomas of the Epididymis
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Papillary cystadenomas of the epididymis occur in approximately 10%–60% of men with VHL disease (5,7). They exist as unilateral lesions in the general population, and when bilateral, are virtually pathognomonic of VHL disease (7). Simple epididymal cysts with no solid component are also commonly found in VHL disease but are also present in 30% of healthy men (5,26), rendering this an unreliable diagnostic sign for the disease.
Papillary cystadenoma of the epididymis is most commonly located in the head of the epididymis but may also involve the spermatic cord. Lesions range in size from 1 to 5 cm but are typically 2–3 cm (7). They are histologically similar to endolymphatic sac cysts and renal cysts (7). Patients may present with a hard smooth "pebble" in the scrotum, and bilateral disease may lead to infertility due to obstructive azoospermia (5,7). Because these lesions are often palpable, imaging is not often required and results are nonspecific. However, at US they are of mixed echotexture, with both solid and cystic elements (Fig 13a). Echogenic shadowing or calcifications may be seen (7). Other findings include ductal ectasia within the rete testis (Fig 13b) and testicular atrophy (7). There is no malignant potential (5,7); therefore, no intervention is required unless there is severe local pain.
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Figure 13a. Papillary cystadenoma of the epididymis. (a) US image of the right testicle shows a solid well-defined tumor that is isoechoic relative to the testicular parenchyma. (b) US image of the left testicle shows simple epididymal cysts with an ectatic, dilated rete testis.
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Figure 13b. Papillary cystadenoma of the epididymis. (a) US image of the right testicle shows a solid well-defined tumor that is isoechoic relative to the testicular parenchyma. (b) US image of the left testicle shows simple epididymal cysts with an ectatic, dilated rete testis.
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Other Lesions
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There have been many reports in the literature of other pathologic conditions arising in patients with VHL disease, which as a result have been attributed to the syndrome. However, it is likely that some may just be coinherited or acquired. For example, multiple cavernous hemangiomas (27) and hepatic cysts (5,28) have been reported, but there does not appear to be an increased prevalence compared with that in the general population. Pulmonary hemangioblastomas (27) have been reported, but it is possible that these represent metastatic foci of cerebellar hemangioblastomas. Reports of pancreatic "hemangiomas" and "hemangioblastomas" (3) may in fact have described neuroendocrine tumors (23).
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Screening for VHL Disease
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A multidisciplinary approach to screening is emphasized; the team, which is led by a geneticist, includes urologists, gastroenterologists, neurologists, ophthalmologists, and radiologists. Care is coordinated by means of regular dedicated VHL disease clinics. Screening protocols will vary between centers, but this is the current screening protocol for VHL disease at our institution, which is also summarized in Table 2:
- For renal screening, annual abdominal US is performed from the age of 10 years. This may be followed up with CT or MR imaging, depending on the US findings. Some centers perform annual CT or MR imaging to screen the kidneys. However, CT has the risk of ionizing radiation, which is a problem when screening asymptomatic patients or at-risk relatives.
- For CNS screening, baseline MR imaging of the brain and spine is performed at age 20 years followed by annual neurologic examinations, with a low threshold for repeat imaging if there are any suspicious signs or symptoms. Some centers perform annual MR imaging to screen the CNS.
- Patients also receive adrenal screening, which consists of 24-hour measurement of urinary vanillylmandelic acid level annually. No imaging is warranted unless this is abnormal. Nevertheless, incidental pheochromocytomas may be detected during routine screening for renal lesions with CT.
- Ophthalmic screening consists of annual direct and indirect ophthalmoscopy from the age of 5 years. Again, no radiologic input is required.
- At our institution, we also are piloting a questionnaire as an auditory screening tool. If the responses to the questionnaire are positive, an audiogram is obtained; if this is abnormal, MR imaging of the internal auditory canal is performed to look for endolymphatic sac tumors.
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Conclusions
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The examples illustrated herein emphasize that the manifestations of VHL disease are protean. Although genetic testing is available, imaging plays a key role in the identification of abnormalities and their subsequent follow-up, in the screening of asymptomatic gene carriers, and in their long-term surveillance. The importance of screening is emphasized because the lesions in VHL disease are treatable; thus, early detection enables more conservative therapy to be performed and may enhance the patient’s length and quality of life.
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Acknowledgments
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We are grateful to Fred Kavalier, MBBS, MRCP, for advice regarding screening protocols and to Steve Connor, MBChB, FRCR, for advice on neuroradiologic aspects of the manuscript.
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Footnotes
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Abbreviations: CNS = central nervous system, MIBG = metaiodobenzylguanidine, RCC = renal cell carcinoma, VHL = von Hippel-Lindau
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References
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- Seizinger BR, Rouleau GA, Ozelius LJ, et al. Von Hippel Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature 1988;332(6161):268–269.[CrossRef][Medline]
- Latif F, Tory K, Gnarra J, et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science 1993;260(5112):1317–1320.[Abstract/Free Full Text]
- Taouli B, Ghouadni M, Corréas JM, et al. Spectrum of abdominal imaging findings in von Hippel-Lindau disease. AJR Am J Roentgenol 2003; 181(4):1049–1054.[Free Full Text]
- Hes FJ, Feldberg MA. Von Hippel-Lindau disease: strategies in early detection (renal-, adrenal-, pancreatic masses). Eur Radiol 1999;9(4):598–610.[CrossRef][Medline]
- Karsdorp N, Elderson A, Wittebol-Post D, et al. Von Hippel Lindau disease: new strategies in early detection and treatment. Am J Med 1994;97(2): 158–168.[CrossRef][Medline]
- Melmon KL, Rosen SW. Lindau’s disease: review of the literature and study of a large kindred. Am J Med 1964;36:595–617.[CrossRef][Medline]
- Choyke PL, Glenn GM, Walther MM, et al. Von Hippel Lindau disease: genetic, clinical, and imaging features. Radiology 1995;194(3):629–642.[Abstract/Free Full Text]
- Friedrich CA. Von Hippel-Lindau syndrome: a pleomorphic condition. Cancer 1999;86(11 suppl):2478–2482.[CrossRef][Medline]
- Conway JE, Chou D, Clatterbuck RE, et al. Hemangioblastomas of the central nervous system in von Hippel-Lindau syndrome and sporadic disease. Neurosurgery 2001;48(1):55–62.[CrossRef][Medline]
- Filling-Katz MR, Choyke PL, Patronas NJ, et al. Radiologic screening for von Hippel-Lindau disease: the role of Gd-DTPA enhanced MR imaging of the CNS. J Comput Assist Tomogr 1989;13(5): 743–755.[Medline]
- Filling-Katz MR, Choyke PL, Oldfield E, et al. Central nervous system involvement in von Hippel-Lindau disease. Neurology 1991;41(1):41–46.[Abstract/Free Full Text]
- Chang SD, Meisel JA, Hancock SL, Martin DP, McManus M, Adler JR Jr. Treatment of hemangioblastomas in von Hippel-Lindau disease with linear accelerator-based radiosurgery. Neurosurgery 1998;43(1):28–34.[Medline]
- Wang EM, Pan L, Wang BJ, et al. The long-term results of gamma knife radiosurgery for hemangioblastomas of the brain. J Neurosurg 2005; 102(suppl):225–229.[Medline]
- Lo WW, Applegate LJ, Carberry JN, et al. Endolymphatic sac tumors: radiologic appearance. Radiology 1993;189(1):199–204.[Abstract/Free Full Text]
- Ayadi K, Mahfoudh KB, Khannous M, Mnif J. Endolymphatic sac tumor and von Hippel-Lindau disease: imaging features. AJR Am J Roentgenol 2000;175(3):925–926.[Free Full Text]
- Choyke PL, Glenn GM, Walther MM, et al. The natural history of renal lesions in von Hippel-Lindau disease: a serial CT study in 28 patients. AJR Am J Roentgenol 1992;159(6):1229–1234.[Abstract/Free Full Text]
- Malek RS, Omess PJ, Benson RC Jr, Zincke H. Renal cell carcinoma in von Hippel-Lindau syndrome. Am J Med 1987;82(2):236–238.[CrossRef][Medline]
- Levine E, Lee KR, Weigel JW, Farber B. Computed tomography in the diagnosis of renal carcinoma complicating Hippel-Lindau syndrome. Radiology 1979;130(3):703–706.[Abstract]
- Choyke PL, Glenn GM, Walther MM, Zbar B, Linehan WM. Hereditary renal cancers. Radiology 2003;226(1):33–46.[Abstract/Free Full Text]
- Gervais DA, Arellano RS, Mueller PR. Percutaneous radiofrequency ablation of renal cell carcinoma. Eur Radiol 2005;15(5):960–967.[CrossRef][Medline]
- Fotiadis NI, Sabharwal T, Morales JP, Hodgson DJ, O’Brien TS, Adam A. Combined percutaneous radiofrequency ablation and ethanol injection of renal tumours: midterm results. Eur Urol 2007; 52(3):777–784.[CrossRef][Medline]
- Neumann HP, Dinkel E, Brambs H, et al. Pancreatic lesions in the von Hippel-Lindau syndrome. Gastroenterology 1991;101(2):465–471.[Medline]
- Hough DM, Stephens DH, Johnson CD, Binkovitz LA. Pancreatic lesions in von Hippel-Lindau disease: prevalence, clinical significance, and CT findings. AJR Am J Roentgenol 1994;162(5): 1091–1094.[Abstract/Free Full Text]
- Marcos HB, Libutti SK, Alexander HR, et al. Neuroendocrine tumors of the pancreas in von Hippel-Lindau disease: spectrum of appearances at CT and MR imaging with histopathologic comparison. Radiology 2002;225(3):751–758.[Abstract/Free Full Text]
- Choyke PL, Filling-Katz MR, Shawker TH, et al. Von Hippel-Lindau disease: radiologic screening for visceral manifestations. Radiology 1990;174(3 pt 1):815–820.[Abstract/Free Full Text]
- Leung ML, Gooding GA, Williams RD. High resolution sonography of scrotal contents in asymptomatic subjects. AJR Am J Roentgenol 1984;143(1):161–164.[Abstract/Free Full Text]
- McGrath FP, Gibney RG, Morris DC, Owen DA, Erb SR. Case report: multiple hepatic and pulmonary haemangioblastomas—a new manifestation of von Hippel-Lindau disease. Clin Radiol 1992; 45(1):37–39.[CrossRef][Medline]
- Horton WA, Wong V, Eldridge R. Von Hippel-Lindau disease: clinical and pathological manifestations in nine families with 50 affected members. Arch Intern Med 1976;136(7):769–777.[Abstract/Free Full Text]
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Abstract
LEARNING OBJECTIVES FOR TEST...
