Vascular tumors of skeletal system: current concepts of classification and diagnosis

Vascular tumors of bone are a heterogeneous group. Numerous terms have been introduced as well as different classification systems. None of the classification schemes have been accepted due to lack of consistent terminology, accepted histologic criteria, and limited correlation with clinical outcome. It is acknowledged that vascular tumors of bone originate from endothelial cells, resulting in variable expression of endothelial markers. None of these markers are useful to discriminate between benign and malignant lesions. Although radiologic appearance is not specific, radiologic multifocality should trigger to include a vascular neoplasm in the differential diagnosis. This review gives an overview of current literature by describing all different histologic subtypes in correspondence with clinical, radiologic and genetic data. We propose the classification of vascular tumors of bone according to the three-tiered World Health Organization classification scheme for soft tissue tumors dividing entities into a benign, intermediate and malignant category. Hemangioma is the most often and commonly recognized benign lesion. Epithelioid hemangioma has been better defined over the past few years. Based on its locally aggressive behavior and occurrence of lymph node metastases, classification within the intermediate category could be considered. Angiosarcoma is the only accepted term for high-grade malignant vascular tumor of bone and so far, epithelioid hemangioendo-thelioma is the only accepted low-grade malignant vascular tumor of bone. It is still unclear whether other low-grade malignant vascular tumors of bone (e.g. hemangioendothelioma) truly exist. Unfortunately, molecular / genetic studies of vascular tumors of bone which might support the proposed classification are very sparse. Introduction Today, vascular tumors of bone consist of a wide variety of different clinicopathologic entities, ranging from benign lesions on one hand and frankly malignant tumors at the other hand. Since the first report on malignant vascular tumors of bone in 1921 by Wells [1], various entities have been described and many different terms have been proposed. Over the years, terms such as angiosarcoma, hemangiosarcoma and hemangioendothelioma have been used sometimes as synonyms or to stress different histologic entities, confusing numerous medical experts [2-6]. Also the classification of vascular tumors of bone is highly controversial, especially considering the lack of consistent terminology, accepted histological criteria, and the limited correlation with clinical outcome. As a consequence, so far none of the suggested classification schemes have been generally accepted [7, 3, 4, 6]. Wenger and Wold acknowledged the confusing terminology and proposed in 2000 a new classification system for benign and malignant vascular tumors and stated that these lesions should be regarded as a spectrum [6, 8]. However, this is still controversial since a spectrum implicates the possibility of progression of a benign lesion towards a malignancy over time and only single case reports have described this phenomenon [9-16]. Since 1942, it is generally accepted that vascular tumors of bone originate from endothelial cells [17]. The exact mechanism or possible genetic aberrations resulting in tumorigenesis still remains unknown. In this review we want to give an overview and update of the current classification of vascular tumors of bone (Table 1) by describing all different histologic subtypes in correspondence with clinical, radiologic and when available genetic or biologic data. Vascular tumors, for which a primary bone origin is extremely rare, are not discussed within this review. Since molecular studies on vascular tumors of bone are sparse, their value in the classification of these lesions is limited