Liver and skin biopsies. (A) Liver biopsy of case 2 shows infiltration of sinusoids by large histiocytes, which on causal examination are difficult to distinguish from the hepatocytes. (B) Liver biopsy of case 1 shows aggregates of histiocytes (arrows) in the sinusoids. The histiocytes have irregularly folded nuclei and abundant lightly eosinophilic cytoplasm. (C) Morphologic spectrum of proliferated histiocytes in the liver sinusoids. The histiocytes have 1 or 2 nuclei, which often show marked irregular foldings and small nucleoli. Some contain phagocytosed blood cells, brown pigment, or fine vacuoles. (D) Skin lesion of case 1 shows dermal infiltrate of mononuclear cells and multinucleated giant cells; the latter showed wreathlike nuclei (upper panel). These cells are immunoreactive for ALK (lower panel). (E) The histiocytes in the sinusoids show positive immunostaining for CD163. (F) Immunostaining for ALK highlights the sinusoidal distribution of the histiocytes (left panel). Higher magnification shows cell membrane and weak cytoplasmic staining (right panel). Images were captured with Olympus DP71 camera mounted on an Olympus microscope model BX61 (Tokyo, Japan). The objectives used for capturing the images were as follow: (A) 20× objective; (B) 100× objective; (C) 100× objective; (D) 40× objective; (E) 60× objective; (F, left) 10× objective; (F, right) 60× objective. Images were acquired using Olympus DP Controller, and whitening of the background and cropping of the images were performed using Adobe Photoshop CS (Adobe Systems, San Jose, CA).