Xanthogranulomatous disease of bone is exceptionally uncommon. Clinically, radiologically and pathologically, it is a great imitator of malignancy. While there are few reports on the surgical pathology of this rare entity, there is no published report on its cytopathologic characteristics. We report herein the case of a 44-year-old male who was evaluated at The Johns Hopkins Hospital for a 2.3-cm painful soft tissue mass present within the medullary canal of the distal tibia with destruction of the overlying cortex. A computed tomography-guided fine needle aspiration biopsy revealed abundant histiocytes and occasional giant cells in an inflammatory background. This was interpreted as a ‘histiocyte-rich lesion,’ and an excisional biopsy was recommended. Subsequent curettage was performed, and the histological material was diagnosed as ‘xanthogranuloma of bone.’ The rarity of xanthogranuloma of bone and its resemblance to the more common reactive and malignant bone neoplasms may present diagnostic challenges.

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