Aneurysmal Bone Cyst

Abstract

Aneurysmal bone cyst (ABC) is a primary bone tumor that predominantly affects individuals in the first 2 decades of life. Imaging studies reveal an osteolytic, eccentric, and multicystic lesion. The neoplasm usually behaves in a benign fashion but may recur locally. Intralesional curettage is the treatment of choice, but surgical resection or other therapeutic approaches have been occasionally used. Aneurysmal bone cyst is characterized by the chromosomal translocation t(16;17)(q22;p13), which results in the fusion of the promoter region of the osteoblast cadherin 11 (CDH11) to the entire coding sequence of the ubiquitin protease USP6 in a classic promoter swapping mechanism. The fusion leads to USP6 transcriptional up-regulation and protein overexpression. Several alternate USP6 fusion genes have also been described, and more recent studies have shown that USP6 contributes to the pathogenesis of ABC via (1) activation of metalloproteases that promote osteolysis and matrix degradation and (2) inhibition of proteins involved in osteoblastic maturation. These new discoveries are enhancing our understanding of ABC biology and may lead to the development of novel therapeutic approaches for this tumor.