Angiosarcoma of Bone

Staging is according to bone sarcoma protocols (see TNM staging of tumors of bone). See also the information on staging in section Bone tumors: Introduction.

Genetic information on angiosarcoma of bone is limited. An array comparative genomic hybridization study distinguished two molecular groups: cases with few or no gross aberrations and cases with numerous genetic aberrations consisting of chromosomal losses, chromosomal gains, and high-level amplifications or complex aberrations. The most common finding was amplification of 2q and 17q, which was also found in angiosarcoma of soft tissue, suggesting overlap in tumorigenesis irrespective of their location. One angiosarcoma of bone was shown to harbor a KDR mutation, while CIC abnormalities were absent. MYC overexpression can be seen in some cases.

The RB1 pathway is involved in tumorigenesis in about 55% of angiosarcomas of bone (loss of p16 and/or overexpression of cyclin D1), whereas overexpression of p53 or MDM2 is absent, suggesting that the p53 pathway is less important. In addition, TGF-β signaling is highly active in angiosarcoma of bone when compared with angiosarcoma of soft tissue. Although the PI3K/AKT pathway is active in angiosarcomas in both bone and soft tissue, different mechanisms seem to be involved: 41% of angiosarcomas of bone show a decrease in expression of PTEN, whereas angiosarcomas of soft tissue overexpress KIT.

Angiosarcoma is usually > 5 cm in greatest dimension, friable, hemorrhagic, and tan-red. The tumor erodes and destroys the cortex and infiltrates into the soft tissues. Areas of necrosis are difficult to identify because of the hemorrhagic appearance of the tumor.

Angiosarcoma is characterized by cytologically malignant cells that are most often epithelioid in appearance (> 90% of cases) and less frequently spindled. The nuclei are usually vesicular and contain one or several small nucleoli or a macronucleolus. The cytoplasm is deeply eosinophilic and often contains one or more vacuoles, which may be clear and empty or may hold intact or fragmented erythrocytes. Mitotic figures are often numerous, and atypical forms can be seen. The tumor cells usually grow in solid sheets; however, in approximately one half of cases, they line irregular vascular lumina. Extravasated erythrocytes can be numerous, and scattered deposits of hemosiderin may also be present. A variable inflammatory infiltrate is present, generally consisting of lymphocytes and neutrophilic or eosinophilic granulocytes. Reactive bone formation can sometimes be observed. In the absence of obvious vascular differentiation, abundant intratumoral hemorrhage and intratumoral neutrophils are useful morphological features that may suggest the diagnosis.

Not clinically relevant

Patients are usually treated with surgery, radiation therapy, and/or chemotherapy. The biological behavior of individual cases is unpredictable, although as a group angiosarcomas of bone are high-grade and clinically extremely aggressive. In a study of 31 patients, the 1-year, 2-year, and 5-year survival rates were 55%, 43%, and 33%, respectively. The presence of a macronucleolus, ≥ 3 mitoses per about 2 mm², and < 5 eosinophilic granulocytes per about 2 mm² within a tumor has been shown to be associated with a worse survival. Lymphangiogenic differentiation as evidenced by D2-40 expression also seems to predict a more aggressive course. Loss of p16 expression is also associated with a significantly worse prognosis.

Not clinically relevant

Essential: primary origin in bone; vasoformative architecture and/or expression of endothelial markers; prominent nuclear atypia and readily observed mitoses.