High Resolution MRI of Xanthogranuloma of Choroid Plexus Induced by Hypercholesterolemia

Introduction: Symptomatic intracranial xanthogranulomas mostly arise in the third ventricle, the choroid plexus of the lateral ventricle and the dura mater, showing hydrocephalus and neurological deficits due to mass effect . Pathological findings of central nervous system xanthogranulomas are not rare (1.6-7%) . Although case reports have shown that such lesions are occasionally associated with hyperlipidemia, arteriosclerosis, diabetes mellitus, familial hyperproteinemia, juvenile xanthogranuloma, colloid cysts, or histiocytosis X, the pathogenesis of this disease is still a matter of debate. Attempting to clarify the etiology of this disease, we fed rabbits a diet rich in cholesterol for an extended period of time. In vivo highresolution MRI and histological studies were performed on brains of these rabbits. Methods: New Zealand white rabbits were fed 0.125-0.25% cholesterol-enriched diets and maintained hypercholesterolemia for 28 months. In vivo high-resolution brain MRI of these rabbits were performed on a 3T scanner interfaced with an insertable gradient coil using 3D FIESTA sequence (100x100x200 μm3; TR/TE, 12/6ms; FA, 20°; BW, 21kHz; phase cycling number/recon, 8/sum-of-squares). Following imaging, brains were dissected after a transcardial perfusion rinse. Hematoxylin and eosin (H&E) staining, Bielschowsky’s silver staining, Oil Red O staining for lipids, Ram11 immunohistochemistry for macrophage cells and CD31 immunostaining for endothelial cells were performed on the 10μm fresh frozen sections or 5 μm paraffin sections of fixed tissues. Results: In vivo high-resolution MRI revealed that 5 of 6 cholesterol fed rabbits developed mass lesions in the choroid plexus. FIESTA images show these masses as tumorous swellings of the choroid plexus with focal areas of hypointensity. The lesions were mainly asymmetrically confined to the choroid plexus of lateral ventricle and ventral fornix in the roof of the third ventricle accompanied by hydrocephalus and remarkable enlargement of the ventricular system (Figure 1). Further histological studies showed that the lesions consisted of characteristic foamy macrophages (histiocytes) and capillary vasculature interspersed among prominent crystalline cholesterol clefts and lipid globules, which is consistent with the histopathology of a xanthogranuloma (Figure 2). Foam cells in and around the xanthogranuloma were positive for macrophage-specific markers. In some cases, the lesions invaded adjacent structures of the brain parenchyma, especially the fornix, hippocampus, and dorsal diencephalons. Conclusion: In vivo high-resolution brain MRI reveals sizable xanthogranulomatous choroid plexus present in the hypercholesterolemic rabbits, which was further confirmed by histological and immunohistochemical examination of these brains. This work supports the view that hyperlipidemia/ hypercholesterolemia are predisposing factors for the formation of xanthogranuloma of the choroid plexus. Ongoing studies will probe this relationship further as well as investigating the connection to other neurodegenerative disorders such as Alzheimer’s disease.