Typical ECD manifestations and bone pathology in patients with ECD and mixed ECD-LCH. (A) Coronal magnetic resonance imaging (MRI) scan showing bilateral symmetric osteosclerosis of tibial meta-diaphysis (arrows). (B) Axial MRI scan of the brain showing bilateral hyperintense lesions of the dentate nuclei (arrows). (C) Sagittal MRI scan of the brain depicting a skull base meningioma-like lesion of the greater sphenoid wing (arrow). (D) Axial MRI scan of the cervical spine showing a bilateral lesion with slight enhancement forming a dumbbell-shaped mass inside the neural foramina at C5-C6 level (arrows). (E) 18F-fluorodeoxyglucose positron emission tomography showing high metabolic activity of tibial metadiaphyseal lesions (arrowheads). (F) Periorbital xanthelasma-like lesions. (G) Axial abdominal computed tomography (CT) scan showing bilateral perinephric infiltrates (“hairy kidneys”) (arrows). (H) Coronal abdominal CT scan showing massive bilateral hydroureteronephrosis in a patient with perinephric ECD infiltrates. (I) High-resolution axial CT scan of the chest demonstrating bilateral interlobular septal thickening and ground-glass opacities. (J) Axial CT scan of the chest showing cardiac pseudotumor (arrows) developed around the right coronary artery and into the right atrioventricular sulcus. (K) Bone biopsy showing an infiltrate comprising numerous foamy histiocytes and a multinucleated Touton cell (arrow) associated with fibrosis. (L) Diffuse infiltration by foamy histiocytes. (M) Classic ECD CD68 immunostaining in a bone biopsy. (N) Mixed lesion showing an area occupied by numerous Langerhans cells with ovoid to reniform nuclei, consistent with LCH (O) and a concomitant area showing numerous foamy histiocytes and multinucleated Touton cells (arrows), consistent with ECD (P). K-L and N-P: Hematoxylin and eosin staining; M: immunohistochemical staining for CD68-PGM1. Original magnification: K, ×20; L, ×40; M, ×10; N, ×2; O-P, ×40.