AJR 2003; 181:1049-1054
© American Roentgen Ray Society
Spectrum of Abdominal Imaging Findings in von Hippel-Lindau Disease
Bachir Taouli1,2,
Mehdi Ghouadni3,
Jean-Michel Corréas3,
Pascal Hammel4,
Anne Couvelard5,
Stéphane Richard6 and
Valérie Vilgrain1
1 Department of Radiology, Hôpital Beaujon, 100, Blvd. du
Général Leclerc, 92118 Clichy, France.
2 Present address: Department of Radiology, University of California, San
Francisco, 505 Parnassus Ave., Box 0628, San Francisco CA 94143-0628.
3 Department of Radiology, Hôpital Necker, Paris, France.
4 Department of Gastroenterology, Hôpital Beaujon, 92118 Clichy,
France.
5 Department of Pathology, Hôpital Beaujon, 92118 Clichy, France.
6 Department of Genetic Oncology, Hôpital du Kremlin-Bicêtre, Le
Kremlin-Bicêtre, France.
Received January 13, 2003;
accepted after revision February 26, 2003.
Address correspondence to B. Taouli.
Introduction
Von Hippel-Lindau disease is a rare autosomal dominant familial tumor
syndrome associated with brain, retinal, and spinal cord hemangioblastomas;
renal cysts and renal cell carcinoma; pheochromocytomas; and pancreatic cysts,
pancreatic serous cystadenomas, and pancreatic neuroendocrine tumors. In this
article, we show the major abdominal imaging features of von Hippel-Lindau
disease using CT and MRI in a large series of more than 150 patients.
Genetics of von Hippel-Lindau Disease
Von Hippel-Lindau disease has a prevalence of one in 39,000–53,000,
with autosomal dominant inheritance, high penetrance, and variable expression.
Von Hippel-Lindau disease is associated with inactivation of a tumor
suppressor gene identified in 1993 in the short arm of chromosome 3
[1]. A wide range of mutations
have been described in von Hippel-Lindau disease; however, as many as 30% of
patients have no exact mutation identified.
Renal Masses
Renal Cysts
Renal cysts are found in 50–75% of patients with von Hippel-Lindau
disease [2]. Renal cysts can be
divided into simple renal cysts and complex renal cysts, which combine cystic
and solid components. The cysts are usually bilateral and multiple. Simple
renal cysts can be diagnosed on sonography, CT (thin-walled lesion with fluid
density with little or no enhancement of the cyst content) (Figs.
1 and
2), and MRI (hypointense on T1-
and hyperintense on T2-weighted images, with no enhancement after gadolinium
injection). Complex cysts are precursors to renal cell carcinoma and require
close follow-up or surgery, depending on the degree of suspicion for
cancer.
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Fig. 1. —50-year-old woman with von Hippel-Lindau disease and renal
and pancreatic cysts. Contrast-enhanced CT scan shows bilateral renal cysts
(thin arrows), solid right renal lesion (straight thick
arrow), and pancreatic cysts (curved arrows).
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Fig. 2. —34-year-old woman with von Hippel-Lindau disease and renal
and pancreatic cysts. Contrast-enhanced CT scan shows bilateral renal cysts
(straight arrows) and large pancreatic cysts (curved
arrows).
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Renal Cell Carcinoma
Renal cell carcinoma occurs in 28–45% of patients with von
Hippel-Lindau disease [3] and
is a frequent cause of morbidity and mortality. On average, renal cell
carcinoma in von Hippel-Lindau disease occurs in patients who are younger
(mean age, 30–36 years)
[4] than those who contract
sporadic forms of renal cell carcinoma. CT is more reliable than sonography
for the detection of renal cancer. MRI (using fast T2- and gadolinium-enhanced
T1-weighted sequences) is an alternative to CT for patients with impaired
renal function and to reduce radiation exposure. In von Hippel-Lindau disease,
renal cell carcinoma often appears as multicentric and bilateral solid
hypovascular renal masses or as complex cystic masses with mural nodules and
thick septa (Figs. 3A,
3B,
3C,
3D,
4A,
4B,
5A,
5B). Nephron-sparing surgery
or, more recently, radiofrequency ablation can be used to maintain renal
function.
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Fig. 3A. —57-year-old man with von Hippel-Lindau disease and previous
partial right nephrectomy for renal cell carcinoma. Contrast-enhanced CT scan
shows multiple cysts of pancreatic head (long arrow), renal cyst
(short straight arrow) on left side, and liver metastasis (curved
arrow).
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Fig. 3B. —57-year-old man with von Hippel-Lindau disease and previous
partial right nephrectomy for renal cell carcinoma. Contrast-enhanced CT scan
obtained at lower level than A shows serous cystadenoma of pancreatic
head (straight arrow) with calcifications, previous partial right
nephrectomy, and small renal cyst (curved arrow) on right side.
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Fig. 3C. —57-year-old man with von Hippel-Lindau disease and previous
partial right nephrectomy for renal cell carcinoma. Contrast-enhanced CT scan
obtained at lower level than B shows vertebral metastasis (curved
arrow) and renal solid mass (straight arrow) on right side
corresponding to renal cell carcinoma.
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Fig. 3D. —57-year-old man with von Hippel-Lindau disease and previous
partial right nephrectomy for renal cell carcinoma. Contrast-enhanced CT scan
obtained at lower level than C shows a second solid renal mass
(arrow) on right side corresponding to another focus of renal cell
carcinoma.
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Fig. 4B. —46-year-old man with von Hippel-Lindau disease and renal cell
carcinoma. Gross macroscopy of specimen from partial right nephrectomy shows
2.5-cm mass corresponding to renal cell carcinoma, with small hemorrhagic
foci.
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Fig. 5B. —47-year-old woman with von Hippel-Lindau disease and previous
total right nephrectomy for renal cell carcinoma. Contrast-enhanced
T1-weighted image shows enhancing solid renal mass (arrow) on left
side corresponding to renal cell carcinoma.
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Pheochromocytomas
Pheochromocytomas develop in fewer than 30% of families with von
Hippel-Lindau disease. They are bilateral in 50% of patients and are usually
benign (malignancy rate, 10–15%), with a high incidence of metachronous
tumors developing after surgery. Most tumors are localized in the adrenal
glands, but 15–18% of the lesions are found in an extraadrenal location
(paragangliomas). The diagnosis is based on biochemical tests (serum and
urinary catecholamines) and imaging. On CT
[5]
(Fig. 6), pheochromocytoma
typically appears as a solid or complex cystic mass with some areas of
necrosis and hemorrhage, possible calcifications, and marked enhancement. On
MRI (Fig. 7A,
7B), pheochromocytoma appears
as iso- or hypointense to the liver on T1-weighted and hyperintense on
T2-weighted images in 95–100% of cases
[5] and shows marked
enhancement after gadolinium injection. Scanning with metaiodobenzylguanidine
shows high uptake in 75–95% of cases. The recent therapeutic trend has
been toward laparoscopic partial adrenalectomy, but the risk of recurrence is
high.
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Fig. 7A. —40-year-old man with von Hippel-Lindau disease and
pheochromocytoma. Fat-saturated T2-weighted image shows adrenal mass
(arrow) on right side that appears heterogeneous and has areas of
high signal intensity.
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Pancreatic Masses
The frequency of pancreatic involvement in von Hippel-Lindau disease is
15–77% [6,
7]. Lesions include simple
pancreatic cysts (91%), serous cystadenomas (12%), neuroendocrine tumors
(7–12%), and combined lesions (11%)
[7,
8]. Pancreatic cystic lesions
are benign, whereas neuroendocrine tumors can be malignant. Pancreatic
adenocarcinoma and hemangioblastoma have also been described in von
Hippel-Lindau disease.
Simple Pancreatic Cysts
In most patients, pancreatic cysts are asymptomatic. However, in some
instances they can cause local compression of adjacent organs, vessels, and
the common bile duct. CT and MRI show multiple pancreatic cysts with no
enhancement after contrast injection (Figs.
1,
2,
3A,
3B,
3C,
3D,
5A,
5B,
8A,
8B, and
9A,
9B).
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Fig. 9A. —51-year-old man with von Hippel-Lindau disease and pancreatic
neuroendocrine tumor who previously underwent left nephrectomy for renal cell
carcinoma. Contrast-enhanced CT scan shows large hypervascular mass (thin
arrow) of pancreatic head corresponding to neuroendocrine tumor, small
neuroendocrine tumor of pancreatic tail with posttreatment cystic changes
(curved arrow), and cysts (straight thick arrow) of
pancreatic head.
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Fig. 9B. —51-year-old man with von Hippel-Lindau disease and pancreatic
neuroendocrine tumor who previously underwent left nephrectomy for renal cell
carcinoma. Photograph of specimen from proximal pancreatectomy shows
correlation of gross macroscopy. Duodenum, neuroendocrine tumor, and main
pancreatic duct are indicated by arrows.
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Serous Cystadenomas
Sonography can show a variety of findings, such as echogenic masses with or
without small cystic portions, multilocular cysts, or mixed hyper- and
hypoechoic masses. On CT, these masses typically appear as microcystic, with a
cluster of numerous small (< 2 cm), well-defined cystic loculi, central
calcifications, enhancement around microcysts after injection of contrast
media, and larger cysts on the periphery of the mass
(Fig. 10). On MRI, serous
cystadenomas have high signal intensity on T2-weighted images. Serous
cystadenomas can be difficult to differentiate from simple cysts at imaging,
and the visualization of enhancing septa favors the diagnosis of microcystic
adenoma. However, the differential diagnosis is not important because these
lesions require no treatment.
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Fig. 10. —42-year-old man with von Hippel-Lindau disease and previous
left nephrectomy for renal cell carcinoma. Contrast-enhanced CT scan shows
serous cystadenoma of pancreatic body and tail with central calcifications
(arrows).
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Pancreatic Neuroendocrine Tumors
Pancreatic neuroendocrine tumors have a low prevalence in von Hippel-Lindau
disease. They are usually nonfunctional and asymptomatic, are often discovered
by screening, have a slow rate of growth, are often multiple, and have no
particular pancreatic location, although a recent study has shown that the
lesions were located in the pancreatic head in more than 50% of patients
[8]. A low incidence of
malignancy has been reported, but metastases can occur in lesions larger than
3 cm [8]. Pancreatic
neuroendocrine tumors appear on CT (Figs.
9A,
9B,
11, and
12A,
12B) and MRI as hypervascular
pancreatic masses, with possible necrotic changes and heterogeneous
enhancement in large lesions. On MRI, these tumors appear hypointense on
T1-weighted and hyperintense on T2-weighted images, but their intensity is not
as high as that of cysts. The treatment is surgery, including proximal or
distal pancreatectomy, depending on the location and the size of the
lesions.
Other Abdominal Lesions
Liver cysts and cystadenomas of the epididymis and of the broad ligament
have been associated with von Hippel-Lindau disease.
Screening of Abdominal Lesions in von Hippel-Lindau Disease
The following tests are recommended
[2] for screening of abdominal
lesions: sonography yearly, beginning at 11 years old; CT yearly or every 2
years, beginning at 20 years old; MRI or metaiodobenzylguanidine scanning as
indicated; and determining the level of urinary catecholamines yearly or every
2 years, beginning at 2 years old. Radiation dose is of concern in these
patients, who have frequent follow-up studies, and sonography or MRI is
preferable.
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Introduction
Genetics of von Hippel-Lindau...
