Imaging manifestations of von Hippel-Lindau disease: an illustrated guide focusing on abdominal manifestations

Abstract

Von Hippel-Lindau (VHL) disease is a monogenic autosomal dominant disorder with germline mutations of the VHL anti-oncogene on the short arm of chromosome 3 (3p25-26). It affects 1:36,000-50,000 individuals, with a penetrance greater than 90% at 65 years of age. Although of variable onset and presentation, with pleiotropism even among members of the same family who share a specific mutation, VHL disease usually manifests initially in young adults. It predisposes to the development of benign and malignant tumors of the central nervous system (CNS) and visceral organs. The clinical diagnosis of VHL disease can be made in the following circumstances: a) in patients with a family history of the disease and at least one of the tumors characteristic of it (e.g., retinal or CNS hemangioblastomas, clear cell renal cell carcinoma, pancreatic neuroendocrine tumors, and endolymphatic sac tumors); b) in patients with two or more CNS hemangioblastomas; c) or in patients with a retinal or CNS hemangioblastoma plus at least one visceral tumor characteristic of the disease, excluding renal and epididymal cysts. Imaging plays an important role in the diagnosis and follow-up of patients with VHL disease. This pictorial essay presents characteristic images of abdominal manifestations of VHL disease-related tumors that all radiologists should be aware of.

Keywords: Carcinoma; Pancreatic neoplasms; Pheochromocytoma; renal cell; von Hippel-Lindau disease/diagnostic imaging.

Figure 1

Axial MRI. T2-weighted sequence (A) and T1-weighted sequence in the corticomedullary phase (B), together with in-phase and out-of-phase T1-weighted gradient-echo sequences (C and D, respectively), showing multiple pancreatic cysts, in both kidneys (black arrows), some containing blood and having a high protein content, presenting as hypervascular, heterogeneous solid nodules (solid white arrows), with an isointense or hyperintense signal on T2-weighted images. In the out-of-phase sequences, note the signal drop (dashed white arrow), reflecting the presence of microscopic fat, in the nodule within the left kidney. Taken together, these findings are characteristic of clear cell RCCs in a patient with VHL disease.

Figure 2

MRI. Axial T2-weighted sequence (A) and three-dimensional cholangiography (B) in a patient with VHL disease, showing that the pancreatic parenchyma had been replaced by numerous diffusely sparse cysts (black arrows). There are also multiple renal cysts, some simple and others with hemorrhagic and high protein content (white arrows). Additional finding: gallbladder stones (A).

Figure 3

Microcystic adenoma (serous cystadenoma) of the pancreas. T2-weighted axial MRI sequence (A) and MRI cholangiography (B), showing a multicystic lesion, composed of clustered microcysts (“honeycomb” appearance), with a fibrotic scar (hypointense signal on T2-weighted imaging) and lobulated contours, without solid components or ductal communication (solid white arrow). Note the lack of dilation of the main pancreatic duct (dashed white arrow).

Figure 4

Contrast-enhanced axial CT scan, in the arterial and nephrographic phases (A and B, respectively), together with a T2-weighted MRI scan (C) and a contrast-enhanced T1-weighted MRI scan, in the arterial phase (D), showing enlargement of the pancreas due to multiple, thin cystic wall lesions (solid white arrow), which have replaced the pancreatic parenchyma, in a patient with VHL disease. Note the well-defined, hypervascular solid lesion in the uncinate process (dashed white arrow) on CT, which may be difficult to visualize in phases other than the arterial phase. On MRI, in addition to arterial hypervascularity, the lesion can be characterized by the hypointense signal on T2-weighted imaging and by the absence of ductal communication.

Figure 5

Contrast-enhanced axial CT scan in the arterial phase (A), showing lesions with intense heterogeneous enhancement in both adrenal glands (black arrows) in a patient with elevated levels of fractionated plasma metanephrines, consistent with pheochromocytomas. In another patient with VHL disease, T2weighted spectral presaturation with inversion recovery MRI sequence (B), together with in-phase and out-of-phase T1-weighted gradient-echo sequences (C and D, respectively), showing a lesion in the left adrenal gland with high signal intensity on the T2-weighted image (solid white arrow) and absence of signal loss in out-of-phase sequences (dashed white arrow), findings typical of a pheochromocytoma.

Figure 6

Paraganglioma. CT (A) and MRI (B,C), showing an expansile, solid lesion in the right, retroperitoneal para-aortic region. The lesion was hypervascular in the arterial phase on CT (white arrow in A) and showed high signal intensity on T2-weighted MRI scans, without microscopic or macroscopic fat foci, with restricted diffusion on diffusion-weighted imaging (black arrows in B and C). Positron-emission tomography/CT with gallium-68 dotatate (D), showing intense avidity of the radiotracer for the lesion (dashed arrow).