Pathogenesis of tendinous xanthoma: histopathological study of the extremities of Watanabe heritable hyperlipidemic rabbits

Background Tendinous xanthomas associated with heritable hyperlipidemia are clinically well known. Nevertheless, there have been few basic investigations of the pathogenesis of these xanthomas. To clarify the pathogenesis of these xanthomas, we examined the localization and histopathological features of xanthomatous tissues in the extremities of Watanabe heritable hyperlipidemic (WHHL) rabbits. Methods Twenty-six WHHL rabbits at 1–31 months of age were dissected to observe the localization of xanthomas. In the histopathological study, tendons and ligaments that included xanthomatous tissues were sectioned and stained with hematoxylin and eosin, Masson's trichrome, and toluidine blue. Immunohistochemical staining was performed with RAM-11, a monoclonal antibody specific for rabbit macrophages, and CD31, a monoclonal antibody specific for endothelial cells. Results At necropsy examination, spontaneous development of xanthomas was observed in the plantar side of the plantaris tendon, the flexor retinaculum of the carpus, and around the digital flexor tendons of each joint level. Xanthoma formation was observed from 10 months of age and progressed with advancing age. The histomorphological study revealed that xanthomas had developed in superficial paratenon of the tendons that wrap around bony or fibrous pulleys. Many fibrocartilage cells were observed in the deep side of affected tendons. A large number of blood vessels were seen in the xanthomatous tissues of these WHHL rabbits. Immunohistochemical evaluation revealed that the xanthoma plaques contained endothelial cells and macrophages. Conclusions It is likely that mechanical stress and extensive vascularization are essential factors for xanthoma formation. Moreover, endothelial cells and macrophages cells are principal contributors to the pathogenesis of tendinous xanthomas and to atherogenesis.